Evaluation of efficacy and safety of fostamatinib monotherapy compared with adalimumab monotherapy in patients with rheumatoid arthritis (RA) - OSKIRA -4

Study identifier:D4300C00004

ClinicalTrials.gov identifier:N/A

EudraCT identifier:2010-023692-26

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

(OSKIRA-4): A Phase IIB, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium Monotherapy Compared with Adalimumab Monotherapy in Patients with Active Rheumatoid Arthritis

Medical condition

Rheumatoid Arthritis

Phase

Phase 2

Healthy volunteers

Study drug

Fostamatinib and placebo injections, Adalimumab and placebo of fostamatinib, Placebo of fostamatinib, fostamatinib, and placebo injections

Sex

All

Actual Enrollment

644

Study type

Interventional

Age

18 Years - 150 Years

Date

Study Start Date: 01 Jan 2011

Primary Completion Date: 01 Oct 2012

Study Completion Date: 01 Aug 2013

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2014 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Plovdiv, Bulgaria

Location

Research Site

Veliko Tarnovo, Bulgaria

Location

Research Site

Sevlievo, Bulgaria

Location

Research Site

Sofia, Bulgaria

Location

Research Site

Pleven, Bulgaria

Location

Research Site

Ruse, Bulgaria

Location

Research Site

Mississauga, ON, Canada

Location

Research Site

Ostrava - Trebovice, Czech Republic

Arms	Assigned Interventions
Experimental: Dosing Group A Oral treatment and subcutaneous injection	Drug: Fostamatinib and placebo injections Fostamatinib 100mg twice daily and placebo injection once every two weeks
Experimental: Dosing Group B Oral treatment and subcutaneous injection	Drug: Fostamatinib and placebo injections Fostamatinib 100mg twice daily / fostamatinib 150mg once daily and placebo injection once every two weeks
Experimental: Dosing Group C Oral treatment and subcutaneous injection	Drug: Fostamatinib and placebo injections Fostamatinib 100mg twice daily / fostamatinib 100mg once daily and placebo injection once every two weeks.
Active Comparator: Dosing Group D Oral treatment and subcutaneous injection	Drug: Adalimumab and placebo of fostamatinib Adalimumab 40mg injection once every two weeks and placebo to fostamatinib twice daily. Other Name: Humira®
Placebo Comparator: Dosing Group E Oral treatment and subcutaneous injection	Drug: Placebo of fostamatinib, fostamatinib, and placebo injections Placebo injection once every two weeks. Placebo to fostamatinib for six weeks, followed by fostamatinib 100mg twice daily (Group F) / fostamatinib 100mg twice daily then 150mg once daily (Group G).

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
452 patients were enrolled into the main study, 173 patients failed screening, 14 did not receive treatment and 265 were treated.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
192 patients enrolled into a separate MRI sub-study (644 enrolled in total). Synovitis results for the MRI sub-study were reported later due to study delays and so are presented entirely separately under NCT02092961

Reporting Groups

	Description
FOSTA 100 MG BID PO	Dosing Group A
FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO	Dosing Group C
ADALIMUMAB 40 MG SC	Dosing Group D
PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO	Dosing Group F
PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO	Dosing Group G

Participant Flow: Overall Study

	FOSTA 100 MG BID PO	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO	ADALIMUMAB 40 MG SC	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO	PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO
STARTED	54^[1]	48^[2]	57^[3]	54^[4]	27^[5]	25^[6]
Randomised but did not receive treatment	2^[7]	5^[8]	2^[9]	3^[10]	2^[11]	0^[12]
COMPLETED	36^[13]	38^[14]	41^[15]	48^[16]	19^[17]	19^[18]
NOT COMPLETED	18	10	16	6	8	6
Not reported	0	0	1	0	0	0
e.g., change in circumstances	8	3	3	3	4	4
Severe non-compliance to protocol	0	0	1	1	0	0
Lack of therapeutic response	1	0	2	1	1	0
Dev. of study specific discont. criteria	2	0	0	0	1	1
Lost to Follow-up	0	0	1	1	0	0
Adverse Event	7	7	8	0	2	1

[1]	Patients who received treatment
[2]	Patients who received treatment
[3]	Patients who received treatment
[4]	Patients who received treatment
[5]	Patients who received treatment
[6]	Patients who received treatment
[7]	Eligibility criteria not fulfilled/subject decision/other
[8]	Eligibility criteria not fulfilled/subject decision/other
[9]	Eligibility criteria not fulfilled/subject decision/other
[10]	Eligibility criteria not fulfilled/subject decision/other
[11]	Eligibility criteria not fulfilled/subject decision/other
[12]	Eligibility criteria not fulfilled/subject decision/other
[13]	Number of patients who completed treatment includes patients who had a dose reduction.
[14]	Number of patients who completed treatment includes patients who had a dose reduction.
[15]	Number of patients who completed treatment includes patients who had a dose reduction.
[16]	Number of patients who completed treatment includes patients who had a dose reduction.
[17]	Number of patients who completed treatment includes patients who had a dose reduction.
[18]	Number of patients who completed treatment includes patients who had a dose reduction.

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
FOSTA 100 MG BID PO	Dosing Group A
FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO	Dosing Group C
ADALIMUMAB 40 MG SC	Dosing Group D
PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO	Dosing Group F
PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO	Dosing Group G

Baseline Measures

	FOSTA 100 MG BID PO	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO	ADALIMUMAB 40 MG SC	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO	PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO	Total
Number of Participants [units: Participants]	54	48	57	54	27	25	265
Age Continuous [units: years] Mean ± Standard Deviation	50 ± 11.5	50 ± 12.6	50 ± 11.0	48 ± 12.4	50 ± 12.7	53 ± 10.8	50 ± 11.8
Gender, Male/Female [units: Participants]
Female	38	39	48	45	20	20	210
Male	16	9	9	9	7	5	55
Race/Ethnicity, Customized [units: Participants]
White	48	47	48	51	23	23	240
Black or African American	5	0	6	1	3	1	16
Asian	1	1	0	1	0	1	4
American Indian or Alaska Native	0	0	1	0	0	0	1
Indian or Pakistani	0	0	1	1	0	0	2
Other	0	0	1	0	1	0	2

Outcome Measures

1. Primary Outcome Measure: DAS28-CRP score - change from baseline to Week 6 compared to placebo [ Time Frame: Baseline and 6 weeks ]

Measure Type	Primary
Measure Name	DAS28-CRP score - change from baseline to Week 6 compared to placebo
Measure Description	DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous.
Time Frame	Baseline and 6 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group E	PLACEBO (COMBINED)

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group E
Number of Participants Analyzed [units:participants]	54	48	57	52
DAS28-CRP score - change from baseline to Week 6 compared to placebo [units: Units on a scale] Mean (Standard Deviation)	1.1 (0.92)	1.1 (1.01)	0.8 (0.96)	0.6 (1.14)

Statistical Analysis 1 for DAS28-CRP score - change from baseline to Week 6 compared to placebo

Groups^[1]	Dosing Group A, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.006
Other^[5]	0.56
90% Confidence Interval	( 0.23 to 0.90 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at Week 6. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Includes terms for baseline as a continuous covariate and treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for DAS28-CRP score - change from baseline to Week 6 compared to placebo

Groups^[1]	Dosing Group B, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.022
Other^[5]	0.49
90% Confidence Interval	( 0.14 to 0.84 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at Week 6. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Includes terms for baseline as a continuous covariate and treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for DAS28-CRP score - change from baseline to Week 6 compared to placebo

Groups^[1]	Dosing Group C, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.280
Other^[5]	0.22
90% Confidence Interval	( -0.12 to 0.56 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at Week 6. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Includes terms for baseline as a continuous covariate and treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: DAS28-CRP score - change from baseline to Week 24 compared to adalimumab [ Time Frame: Baseline and 24 weeks ]

Measure Type	Primary
Measure Name	DAS28-CRP score - change from baseline to Week 24 compared to adalimumab
Measure Description	DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous.
Time Frame	Baseline and 24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group F	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO
Dosing Group G	PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group F	Dosing Group G
Number of Participants Analyzed [units:participants]	54	48	57	54	27	25
DAS28-CRP score - change from baseline to Week 24 compared to adalimumab [units: Units on a scale] Mean (Standard Deviation)	1.0 (1.31)	1.1 (1.22)	1.0 (1.25)	1.8 (1.45)	1.1 (1.26)	1.4 (1.26)

Statistical Analysis 1 for DAS28-CRP score - change from baseline to Week 24 compared to adalimumab

Groups^[1]	Dosing Group A, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
P-Value^[4]	0.005
Other^[5]	-0.72
80% Confidence Interval	( -1.04 to -0.40 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at Week 24. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	For the comparison with adalimumab a non-inferiority margin of -0.6 in the mean change from baseline in DAS28-CRP at Week 24 was defined. The lower 80% confidence interval for treatment difference was below this value so non-inferiority could not be concluded. A p-value is also provided for a 2-sided test of superiority.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Includes terms for baseline as a continuous covariate and treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for DAS28-CRP score - change from baseline to Week 24 compared to adalimumab

Groups^[1]	Dosing Group B, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
P-Value^[4]	0.020
Other^[5]	-0.61
80% Confidence Interval	( -0.94 to -0.27 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at Week 24. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	For the comparison with adalimumab a non-inferiority margin of -0.6 in the mean change from baseline in DAS28-CRP at Week 24 was defined. The lower 80% confidence interval for treatment difference was below this value so non-inferiority could not be concluded. A p-value is also provided for a 2-sided test of superiority.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Includes terms for baseline as a continuous covariate and treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for DAS28-CRP score - change from baseline to Week 24 compared to adalimumab

Groups^[1]	Dosing Group C, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
P-Value^[4]	0.004
Other^[5]	-0.72
80% Confidence Interval	( -1.04 to -0.40 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Change from baseline at Week 24. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	For the comparison with adalimumab a non-inferiority margin of -0.6 in the mean change from baseline in DAS28-CRP at Week 24 was defined. The lower 80% confidence interval for treatment difference was below this value so non-inferiority could not be concluded. A p-value is also provided for a 2-sided test of superiority.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Includes terms for baseline as a continuous covariate and treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: DAS28 EULAR response at Week 6 [ Time Frame: 6 weeks ]

Measure Type	Secondary
Measure Name	DAS28 EULAR response at Week 6
Measure Description	Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. Non-responder imputation has been applied by carrying the baseline observation forward. bid = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, qd = once a day, SC = subcutaneous.
Time Frame	6 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group E	PLACEBO (COMBINED)

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group E
Number of Participants Analyzed [units:participants]	54	48	57	54	52
DAS28 EULAR response at Week 6 [units: Percentage of responders]
No response	37.0	33.3	57.9	40.7	67.3
Moderate response	53.7	47.9	35.1	38.9	25.0
Good response	9.3	18.8	7.0	20.4	7.7

Statistical Analysis 1 for DAS28 EULAR response at Week 6

Groups^[1]	Dosing Group A, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Proportional odds model]
P-Value^[4]	0.005
Odds Ratio (OR)^[5]	3.05
90% Confidence Interval	( 1.59 to 5.86 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	An odds ratio >1 indicates a benefit towards fostamatinib.

Statistical Analysis 2 for DAS28 EULAR response at Week 6

Groups^[1]	Dosing Group B, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Proportional odds model]
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	4.11
90% Confidence Interval	( 2.10 to 8.05 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	An odds ratio >1 indicates a benefit towards fostamatinib.

Statistical Analysis 3 for DAS28 EULAR response at Week 6

Groups^[1]	Dosing Group C, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Proportional odds model]
P-Value^[4]	0.335
Odds Ratio (OR)^[5]	1.47
90% Confidence Interval	( 0.76 to 2.83 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	An odds ratio >1 indicates a benefit towards fostamatinib.

4. Secondary Outcome Measure: DAS28 EULAR response at Week 24 [ Time Frame: 24 weeks ]

Measure Type	Secondary
Measure Name	DAS28 EULAR response at Week 24
Measure Description	Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. Non-responder imputation has been applied by carrying the baseline observation forward. bid = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, qd = once a day, SC = subcutaneous.
Time Frame	24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group F	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO
Dosing Group G	PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group F	Dosing Group G
Number of Participants Analyzed [units:participants]	54	48	57	54	27	25
DAS28 EULAR response at Week 24 [units: Percentage of responders]
No response	51.9	41.7	52.6	31.5	55.6	40.0
Moderate response	29.6	39.6	29.8	27.8	33.3	36.0
Good response	18.5	18.8	17.5	40.7	11.1	24.0

Statistical Analysis 1 for DAS28 EULAR response at Week 24

Groups^[1]	Dosing Group A, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Proportional odds model]
P-Value^[4]	0.007
Odds Ratio (OR)^[5]	0.37
90% Confidence Interval	( 0.20 to 0.68 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	An odds ratio >1 indicates a benefit towards fostamatinib.

Statistical Analysis 2 for DAS28 EULAR response at Week 24

Groups^[1]	Dosing Group B, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Proportional odds model]
P-Value^[4]	0.051
Odds Ratio (OR)^[5]	0.48
90% Confidence Interval	( 0.26 to 0.89 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	An odds ratio >1 indicates a benefit towards fostamatinib.

Statistical Analysis 3 for DAS28 EULAR response at Week 24

Groups^[1]	Dosing Group C, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Proportional odds model]
P-Value^[4]	0.004
Odds Ratio (OR)^[5]	0.36
90% Confidence Interval	( 0.20 to 0.65 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	An odds ratio >1 indicates a benefit towards fostamatinib.

5. Secondary Outcome Measure: Proportion of patients achieving ACR20 up to Week 24 [ Time Frame: 6 and 24 weeks ]

Measure Type	Secondary
Measure Name	Proportion of patients achieving ACR20 up to Week 24
Measure Description	ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Time Frame	6 and 24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6 and with adalimumab (not placebo) at Week 24.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group E	PLACEBO (COMBINED)
Dosing Group F	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO
Dosing Group G	PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group E	Dosing Group F	Dosing Group G
Number of Participants Analyzed [units:participants]	54	48	57	54	52	27	25
Proportion of patients achieving ACR20 up to Week 24 [units: Percentage of responders]
Week 6	48.1	47.9	38.6	53.7	19.2	n/a^[1]	n/a^[2]
Week 24	40.7	56.3	35.1	59.3	n/a^[3]	44.4	44.0

[1]	Data appears under Group E at Week 6.
[2]	Data appears under Group E at Week 6.
[3]	Data appears under Groups F and G at Week 24.

Statistical Analysis 1 for Proportion of patients achieving ACR20 up to Week 24

Groups^[1]	Dosing Group A, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	<0.001
Other^[5]	0.29
90% Confidence Interval	( 0.17 to 0.40 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 6
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 2 for Proportion of patients achieving ACR20 up to Week 24

Groups^[1]	Dosing Group B, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	<0.001
Other^[5]	0.30
90% Confidence Interval	( 0.18 to 0.43 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 6
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 3 for Proportion of patients achieving ACR20 up to Week 24

Groups^[1]	Dosing Group C, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.007
Other^[5]	0.19
90% Confidence Interval	( 0.07 to 0.31 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 6
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 4 for Proportion of patients achieving ACR20 up to Week 24

Groups^[1]	Dosing Group A, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.049
Other^[5]	-0.16
90% Confidence Interval	( -0.30 to -0.03 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 5 for Proportion of patients achieving ACR20 up to Week 24

Groups^[1]	Dosing Group B, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.803
Other^[5]	-0.02
90% Confidence Interval	( -0.16 to 0.12 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 6 for Proportion of patients achieving ACR20 up to Week 24

Groups^[1]	Dosing Group C, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.003
Other^[5]	-0.24
90% Confidence Interval	( -0.37 to -0.10 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

6. Secondary Outcome Measure: Proportion of patients achieving ACR50 up to Week 24 [ Time Frame: 6 and 24 weeks ]

Measure Type	Secondary
Measure Name	Proportion of patients achieving ACR50 up to Week 24
Measure Description	ACR50: American College of Rheumatology 50% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Time Frame	6 and 24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6 and with adalimumab (not placebo) at Week 24.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group E	PLACEBO (COMBINED)
Dosing Group F	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO
Dosing Group G	PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group E	Dosing Group F	Dosing Group G
Number of Participants Analyzed [units:participants]	54	48	57	54	52	27	25
Proportion of patients achieving ACR50 up to Week 24 [units: Percentage of responders]
Week 6	13.0	12.5	7.0	25.9	3.8	n/a^[1]	n/a^[2]
Week 24	20.4	18.8	12.3	31.5	n/a^[3]	22.2	24.0

[1]	Data appears under Group E at Week 6.
[2]	Data appears under Group E at Week 6.
[3]	Data appears under Groups F and G at Week 24.

Statistical Analysis 1 for Proportion of patients achieving ACR50 up to Week 24

Groups^[1]	Dosing Group A, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.059
Other^[5]	0.09
90% Confidence Interval	( 0.01 to 0.18 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 6
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 2 for Proportion of patients achieving ACR50 up to Week 24

Groups^[1]	Dosing Group B, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.071
Other^[5]	0.09
90% Confidence Interval	( 0.01 to 0.17 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 6
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 3 for Proportion of patients achieving ACR50 up to Week 24

Groups^[1]	Dosing Group C, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.758
Other^[5]	0.01
90% Confidence Interval	( -0.05 to 0.07 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 6
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 4 for Proportion of patients achieving ACR50 up to Week 24

Groups^[1]	Dosing Group A, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.114
Other^[5]	-0.12
90% Confidence Interval	( -0.24 to 0.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 5 for Proportion of patients achieving ACR50 up to Week 24

Groups^[1]	Dosing Group B, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.078
Other^[5]	-0.14
90% Confidence Interval	( -0.26 to -0.01 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 6 for Proportion of patients achieving ACR50 up to Week 24

Groups^[1]	Dosing Group C, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.003
Other^[5]	-0.21
90% Confidence Interval	( -0.32 to -0.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

7. Secondary Outcome Measure: Proportion of patients achieving ACR70 up to Week 24 [ Time Frame: 6 and 24 weeks ]

Measure Type	Secondary
Measure Name	Proportion of patients achieving ACR70 up to Week 24
Measure Description	ACR70: American College of Rheumatology 70% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Time Frame	6 and 24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6 and with adalimumab (not placebo) at Week 24.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group E	PLACEBO (COMBINED)
Dosing Group F	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO
Dosing Group G	PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group E	Dosing Group F	Dosing Group G
Number of Participants Analyzed [units:participants]	54	48	57	54	52	27	25
Proportion of patients achieving ACR70 up to Week 24 [units: Percentage of responders]
Week 6	1.9	4.2	1.8	7.4	3.8	n/a^[1]	n/a^[2]
Week 24	9.3	10.4	3.5	20.4	n/a^[3]	7.4	4.0

[1]	Data appears under Group E at Week 6.
[2]	Data appears under Group E at Week 6.
[3]	Data appears under Groups F and G at Week 24.

Statistical Analysis 1 for Proportion of patients achieving ACR70 up to Week 24

Groups^[1]	Dosing Group A, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.460
Other^[5]	-0.02
90% Confidence Interval	( -0.07 to 0.03 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 6
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 2 for Proportion of patients achieving ACR70 up to Week 24

Groups^[1]	Dosing Group B, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.903
Other^[5]	0.00
90% Confidence Interval	( -0.05 to 0.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 6
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 3 for Proportion of patients achieving ACR70 up to Week 24

Groups^[1]	Dosing Group C, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.172
Other^[5]	-0.03
90% Confidence Interval	( -0.08 to 0.01 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 6
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 4 for Proportion of patients achieving ACR70 up to Week 24

Groups^[1]	Dosing Group A, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.082
Other^[5]	-0.11
90% Confidence Interval	( -0.21 to -0.01 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 5 for Proportion of patients achieving ACR70 up to Week 24

Groups^[1]	Dosing Group B, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.092
Other^[5]	-0.11
90% Confidence Interval	( -0.21 to -0.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

Statistical Analysis 6 for Proportion of patients achieving ACR70 up to Week 24

Groups^[1]	Dosing Group C, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mantel Haenszel
P-Value^[4]	0.002
Other^[5]	-0.17
90% Confidence Interval	( -0.27 to -0.08 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	p-values are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24
[5]	Other relevant estimation information:
	90% confidence intervals are calculated using a Mantel-Haenszel approach stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.

8. Secondary Outcome Measure: ACRn - comparison between fostamatinib and placebo at Week 6 [ Time Frame: Baseline and 6 weeks ]

Measure Type	Secondary
Measure Name	ACRn - comparison between fostamatinib and placebo at Week 6
Measure Description	ACRn: American College of Rheumatology Index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints) or in blood test measures of inflammation (such as CRP) or the physician and patient's own asessment of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome and negative values a worsening of clinical condition. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. Mean refers to change at Week 6. Treatment difference: difference between fostamatinib and placebo groups.
Time Frame	Baseline and 6 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group E	PLACEBO (COMBINED)

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group E
Number of Participants Analyzed [units:participants]	54	48	57	54	52
ACRn - comparison between fostamatinib and placebo at Week 6 [units: Percentage change from baseline] Mean (Standard Deviation)	16.60 (30.682)	15.07 (33.334)	6.48 (32.237)	15.53 (43.015)	-6.49 (35.159)

Statistical Analysis 1 for ACRn - comparison between fostamatinib and placebo at Week 6

Groups^[1]	Dosing Group A, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Van Elteren]
P-Value^[4]	<0.001
Other^[5]	23.39
90% Confidence Interval	( 9.57 to 40.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimated using the Van Elteren test stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for ACRn - comparison between fostamatinib and placebo at Week 6

Groups^[1]	Dosing Group B, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Van Elteren]
P-Value^[4]	0.006
Other^[5]	22.97
90% Confidence Interval	( 7.84 to 38.34 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimated using the Van Elteren test stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for ACRn - comparison between fostamatinib and placebo at Week 6

Groups^[1]	Dosing Group C, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Van Elteren]
P-Value^[4]	0.234
Other^[5]	5.72
90% Confidence Interval	( -3.20 to 21.68 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimated using the Van Elteren test stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

9. Secondary Outcome Measure: ACRn - comparison between fostamatinib and adalimumab at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	ACRn - comparison between fostamatinib and adalimumab at Week 24
Measure Description	ACRn: American College of Rheumatology Index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints) or in blood test measures of inflammation (such as CRP) or the physician and patient's own asessment of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome and negative values a worsening of clinical condition. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. Mean refers to change at Week 24. Treatment difference: difference between fostamatinib and adalimumab groups.
Time Frame	Baseline and 24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D
Number of Participants Analyzed [units:participants]	54	48	57	54
ACRn - comparison between fostamatinib and adalimumab at Week 24 [units: Percentage change from baseline] Mean (Standard Deviation)	18.35 (34.355)	22.03 (32.361)	11.49 (26.916)	31.21 (39.187)

Statistical Analysis 1 for ACRn - comparison between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group A, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Van Elteren]
P-Value^[4]	0.030
Other^[5]	-13.72
90% Confidence Interval	( -25.01 to 0.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimated using the Van Elteren test stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for ACRn - comparison between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group B, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Van Elteren]
P-Value^[4]	0.207
Other^[5]	-9.49
90% Confidence Interval	( -25.00 to 6.96 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimated using the Van Elteren test stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for ACRn - comparison between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group C, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Van Elteren]
P-Value^[4]	0.002
Other^[5]	-19.53
90% Confidence Interval	( -30.01 to -6.25 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimated using the Van Elteren test stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant) and pooled country.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

10. Secondary Outcome Measure: HAQ-DI - comparison of the change from baseline between fostamatinib and placebo at Week 6 [ Time Frame: Baseline and 6 weeks ]

Measure Type	Secondary
Measure Name	HAQ-DI - comparison of the change from baseline between fostamatinib and placebo at Week 6
Measure Description	HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Time Frame	Baseline and 6 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group E	PLACEBO (COMBINED)

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group E
Number of Participants Analyzed [units:participants]	54	48	57	54	52
HAQ-DI - comparison of the change from baseline between fostamatinib and placebo at Week 6 [units: Units on a scale] Mean (Standard Deviation)	0.3 (0.35)	0.3 (0.54)	0.2 (0.43)	0.3 (0.45)	0.1 (0.52)

Statistical Analysis 1 for HAQ-DI - comparison of the change from baseline between fostamatinib and placebo at Week 6

Groups^[1]	Dosing Group A, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.007
Other^[5]	0.24
90% Confidence Interval	( 0.09 to 0.38 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Including terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for HAQ-DI - comparison of the change from baseline between fostamatinib and placebo at Week 6

Groups^[1]	Dosing Group B, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.016
Other^[5]	0.22
90% Confidence Interval	( 0.07 to 0.37 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Including terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for HAQ-DI - comparison of the change from baseline between fostamatinib and placebo at Week 6

Groups^[1]	Dosing Group C, Dosing Group E
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.094
Other^[5]	0.14
90% Confidence Interval	( 0.00 to 0.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Includes terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

11. Secondary Outcome Measure: HAQ-DI - comparison of the change from baseline between fostamatinib and adalimumab at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	HAQ-DI - comparison of the change from baseline between fostamatinib and adalimumab at Week 24
Measure Description	HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Time Frame	Baseline and 24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group F	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO
Dosing Group G	PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group F	Dosing Group G
Number of Participants Analyzed [units:participants]	54	48	57	54	27	25
HAQ-DI - comparison of the change from baseline between fostamatinib and adalimumab at Week 24 [units: Units on a scale] Mean (Standard Deviation)	0.3 (0.57)	0.4 (0.56)	0.2 (0.45)	0.5 (0.53)	0.3 (0.47)	0.1 (0.35)

Statistical Analysis 1 for HAQ-DI - comparison of the change from baseline between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group A, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.043
Other^[5]	-0.20
90% Confidence Interval	( -0.36 to -0.04 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Including terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for HAQ-DI - comparison of the change from baseline between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group B, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.158
Other^[5]	-0.14
90% Confidence Interval	( -0.31 to 0.02 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Including terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for HAQ-DI - comparison of the change from baseline between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group C, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.001
Other^[5]	-0.32
90% Confidence Interval	( -0.47 to -0.16 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Includes terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

12. Secondary Outcome Measure: SF-36 - comparison of the change in PCS from baseline between fostamatinib and adalimumab at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	SF-36 - comparison of the change in PCS from baseline between fostamatinib and adalimumab at Week 24
Measure Description	SF-36: 36 item short form health survey, as a measure of health-related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0 to 100. The physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with a mean of 50, standard deviation of 10. A higher score represents a better quality of life. Mean changes from baseline score are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Mean refers to change in scores at Week 24. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, PO = orally, QD = once a day, QoL = quality of life, SC = subcutaneous
Time Frame	Baseline and 24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group F	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO
Dosing Group G	PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group F	Dosing Group G
Number of Participants Analyzed [units:participants]	54	48	57	54	27	25
SF-36 - comparison of the change in PCS from baseline between fostamatinib and adalimumab at Week 24 [units: Units on a scale] Mean (Standard Deviation)	4 (7.3)	5 (7.2)	4 (7.4)	7 (8.4)	4 (8.7)	3 (5.0)

Statistical Analysis 1 for SF-36 - comparison of the change in PCS from baseline between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group A, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.050
Other^[5]	-2.77
90% Confidence Interval	( -5.08 to -0.45 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Including terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for SF-36 - comparison of the change in PCS from baseline between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group B, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.360
Other^[5]	-1.33
90% Confidence Interval	( -3.73 to 1.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Including terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for SF-36 - comparison of the change in PCS from baseline between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group C, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.032
Other^[5]	-2.99
90% Confidence Interval	( -5.29 to -0.70 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Includes terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

13. Secondary Outcome Measure: SF-36 - comparison of the change in MCS from baseline between fostamatinib and adalimumab at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	SF-36 - comparison of the change in MCS from baseline between fostamatinib and adalimumab at Week 24
Measure Description	SF-36: 36 item short form health survey, as a measure of health-related quality of life. The SF-36 scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0 to 100. The physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with a mean of 50, standard deviation of 10. A higher score represents a better quality of life. Mean changes from baseline score are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Mean refers to change in score at Week 24. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once daily.
Time Frame	Baseline and 24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group B	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO
Dosing Group C	FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group F	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO
Dosing Group G	PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO

Measured Values

	Dosing Group A	Dosing Group B	Dosing Group C	Dosing Group D	Dosing Group F	Dosing Group G
Number of Participants Analyzed [units:participants]	54	48	57	54	27	25
SF-36 - comparison of the change in MCS from baseline between fostamatinib and adalimumab at Week 24 [units: Units on a scale] Mean (Standard Deviation)	3 (9.3)	3 (11.5)	2 (10.0)	4 (9.8)	3 (5.9)	0 (10.1)

Statistical Analysis 1 for SF-36 - comparison of the change in MCS from baseline between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group A, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.568
Other^[5]	-1.02
90% Confidence Interval	( -3.95 to 1.92 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Including terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for SF-36 - comparison of the change in MCS from baseline between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group B, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.368
Other^[5]	-1.66
90% Confidence Interval	( -4.69 to 1.38 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Including terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for SF-36 - comparison of the change in MCS from baseline between fostamatinib and adalimumab at Week 24

Groups^[1]	Dosing Group C, Dosing Group D
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.160
Other^[5]	-2.48
90% Confidence Interval	( -5.38 to 0.43 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Includes terms for baseline as a continuous covariate & treatment, DMARD naivety (DMARD naive vs DMARD-IR/intolerant) & pooled country as factors.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

14. Other Pre-specified Outcome Measure: Sub-study: OMERACT RAMRIS synovitis score - comparison between fostamatinib and placebo (Van Elteren) [ Time Frame: 6 weeks ]

Measure Type	Other Pre-specified
Measure Name	Sub-study: OMERACT RAMRIS synovitis score - comparison between fostamatinib and placebo (Van Elteren)
Measure Description	OMERACT RAMRIS synovitis score was based on 8 joints and ranged from 0 to 24 with a smaller value indicating a better clinical condition. bid = twice daily, CI = confidence interval, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, MRI = magnetic resonance imaging, n/a = not available, OMERACT = Outcome Measures in Rheumatoid Arthritis Clinical Trials, PO = orally, RAMRIS = Rheumatoid Arthritis Magnetic Resonance Image Scoring system, SC = subcutaneous. Median refers to change in scores at Week 6. Treatment difference: difference between fostamatinib and placebo groups.
Time Frame	6 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The sub-study analysis set includes those patients who received at least 1 dose of investigational product in the MRI sub-study. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6.

Reporting Groups

	Description
Dosing Group A	FOSTA 100 MG BID PO
Dosing Group D	ADALIMUMAB 40 MG SC
Dosing Group F	PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO

Measured Values

	Dosing Group A	Dosing Group D	Dosing Group F
Number of Participants Analyzed [units:participants]	25	22	20
Sub-study: OMERACT RAMRIS synovitis score - comparison between fostamatinib and placebo (Van Elteren) [units: Units on a scale] Median (Inter-Quartile Range)	-1.50 (-3.00 to 0.00)	-0.50 (-1.00 to 0.00)	0.00 (-0.50 to 1.63)

Statistical Analysis 1 for Sub-study: OMERACT RAMRIS synovitis score - comparison between fostamatinib and placebo (Van Elteren)

Groups^[1]	Dosing Group A, Dosing Group F
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Van Elteren]
P-Value^[4]	0.022
Other^[5]	-1.75
90% Confidence Interval	( -2.75 to -0.42 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimated using the Van Elteren test stratified by DMARD naivety (DMARD naive vs DMARD-IR/intolerant).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	A negative value for change from baseline in OMERACT RAMRIS synovitis score indicates a better clinical condition.
[5]	Other relevant estimation information:
	The point estimate for the median difference in change from baseline and associated 90% CI was calculated using the method of unstratified Hodges-Lehmann. A treatment difference <0 indicates a benefit towards fostamatinib.

Serious Adverse Events

Time Frame	24 weeks
Additional Description	For placebo treated patients time frame includes both placebo(6 weeks) and fostamatinib(18 weeks) treatment. 1 SAE occurred in these treatment arms began during the 6 week placebo treated period

Reporting Groups

	Description
ADALIMUMAB 40 MG	Dosing Group D
FOSTA 100 MG BID	Dosing Group A
PLACEBO (6 WKS) THEN FOSTA 100 MG BID - FOSTA period	Dosing Group C
PLACEBO (6 WKS) THEN FOSTA 100 MG BID - Placebo period	No text entered.
PLACEBO (6 WKS) THEN FOSTA 100 MG BID (4 WKS) THEN 150 MG QD - Placebo period	No text entered.
PLACEBO (6 WKS) THEN FOSTA 100 MG BID (4 WKS) THEN 150 MG QD - FOSTA period	No text entered.

Serious Adverse Events

ADALIMUMAB 40 MG

FOSTA 100 MG BID

PLACEBO (6 WKS) THEN FOSTA 100 MG BID - FOSTA period

PLACEBO (6 WKS) THEN FOSTA 100 MG BID - Placebo period

PLACEBO (6 WKS) THEN FOSTA 100 MG BID (4 WKS) THEN 150 MG QD - Placebo period

PLACEBO (6 WKS) THEN FOSTA 100 MG BID (4 WKS) THEN 150 MG QD - FOSTA period

Total, serious adverse events

# participants affected / at risk

3/54 (5.56%)

0/27 (0.00%)

1/27 (3.70%)

0/25 (0.00%)

VASCULAR DISORDERS

ORTHOSTATIC HYPOTENSION¹,^†

# participants affected / at risk

1/54 (1.85%)

0/54 (0.00%)

0/27 (0.00%)

---/25

# events

INFECTIONS AND INFESTATIONS

GASTROENTERITIS¹,^†

# participants affected / at risk

0/54 (0.00%)

1/54 (1.85%)

0/27 (0.00%)

---/25

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

FEMORAL NECK FRACTURE¹,^†

# participants affected / at risk

0/54 (0.00%)

1/54 (1.85%)

0/27 (0.00%)

---/25

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

POST PROCEDURAL HAEMORRHAGE¹,^†

# participants affected / at risk

0/54 (0.00%)

1/54 (1.85%)

0/27 (0.00%)

---/25

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

EXOSTOSIS¹,^†

# participants affected / at risk

0/54 (0.00%)

0/27 (0.00%)

1/27 (3.70%)

---/25

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

INTERVERTEBRAL DISC PROTRUSION¹,^†

# participants affected / at risk

0/54 (0.00%)

0/27 (0.00%)

1/27 (3.70%)

---/25

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

MUSCULOSKELETAL CHEST PAIN¹,^†

# participants affected / at risk

1/54 (1.85%)

0/54 (0.00%)

0/27 (0.00%)

---/25

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

ASTHMA¹,^†

# participants affected / at risk

1/54 (1.85%)

0/54 (0.00%)

0/27 (0.00%)

---/25

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 15.1

Other Adverse Events

Time Frame	24 weeks
Additional Description	For placebo treated patients time frame includes both placebo(6 weeks) and fostamatinib(18 weeks) treatment. 1 SAE occurred in these treatment arms began during the 6 week placebo treated period

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
ADALIMUMAB 40 MG	Dosing Group D
FOSTA 100 MG BID	Dosing Group A
PLACEBO (6 WKS) THEN FOSTA 100 MG BID - FOSTA period	Dosing Group C
PLACEBO (6 WKS) THEN FOSTA 100 MG BID - Placebo period	No text entered.
PLACEBO (6 WKS) THEN FOSTA 100 MG BID (4 WKS) THEN 150 MG QD - Placebo period	No text entered.
PLACEBO (6 WKS) THEN FOSTA 100 MG BID (4 WKS) THEN 150 MG QD - FOSTA period	No text entered.

Other Adverse Events

ADALIMUMAB 40 MG

FOSTA 100 MG BID

PLACEBO (6 WKS) THEN FOSTA 100 MG BID - FOSTA period

PLACEBO (6 WKS) THEN FOSTA 100 MG BID - Placebo period

PLACEBO (6 WKS) THEN FOSTA 100 MG BID (4 WKS) THEN 150 MG QD - Placebo period

PLACEBO (6 WKS) THEN FOSTA 100 MG BID (4 WKS) THEN 150 MG QD - FOSTA period

Total, other (not including serious) adverse events

# participants affected / at risk

3/54 (5.56%)

14/54 (25.93%)

6/27 (22.22%)

4/27 (14.81%)

0/25 (0.00%)

INFECTIONS AND INFESTATIONS

NASOPHARYNGITIS¹,^†

# participants affected / at risk

1/54 (1.85%)

3/54 (5.56%)

2/27 (7.41%)

0/27 (0.00%)

---/25

# events

GASTROINTESTINAL DISORDERS

CONSTIPATION¹,^†

# participants affected / at risk

0/54 (0.00%)

3/54 (5.56%)

0/27 (0.00%)

---/25

# events

GASTROINTESTINAL DISORDERS

DIARRHOEA¹,^†

# participants affected / at risk

1/54 (1.85%)

3/54 (5.56%)

1/27 (3.70%)

---/25

# events

INFECTIONS AND INFESTATIONS

GASTROENTERITIS¹,^†

# participants affected / at risk

0/54 (0.00%)

2/27 (7.41%)

0/27 (0.00%)

---/25

# events

INVESTIGATIONS

ALANINE AMINOTRANSFERASE INCREASED¹,^†

# participants affected / at risk

0/54 (0.00%)

3/54 (5.56%)

0/27 (0.00%)

---/25

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

RHEUMATOID ARTHRITIS¹,^†

# participants affected / at risk

1/54 (1.85%)

2/54 (3.70%)

2/27 (7.41%)

1/27 (3.70%)

---/25

# events

NERVOUS SYSTEM DISORDERS

HEADACHE¹,^†

# participants affected / at risk

0/54 (0.00%)

0/27 (0.00%)

2/27 (7.41%)

---/25

# events

VASCULAR DISORDERS

HYPERTENSION¹,^†

# participants affected / at risk

0/54 (0.00%)

4/54 (7.41%)

1/27 (3.70%)

---/25

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 15.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The disclosure restriction on the PI is that the sponsor can review and comment on results communications prior to publication. Sponsor will be allowed a review period of at least 60 days from submission but can request that publication be delayed for a period up to 6 months. Any reasonable comments made by the sponsor will be incorporated by the PI into the publication.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Dave Goldstraw
Organization:	AstraZeneca Pharmaceuticals
Phone	+44 (0)1625 512415
E-mail:	[email protected]

Documents available

CSR Synopsis
Download
CSP Redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

ClinicalTrialTransparency@astrazeneca.com

Investigators

Principal Investigator

Neil MacKillop

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site