Evaluation of efficacy and safety of tralokinumab in patients with active, moderate-to-severe ulcerative colitis

Study identifier:D2211C00001

ClinicalTrials.gov identifier:NCT01482884

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A phase IIa, randomised, double-blind, placebo-controlled, parallel-arm, multicenter study to evaluate the efficacy and safety of tralokinumab (CAT-354), a recombinant human monoclonal antibody directed against interleukin-13 (IL-13), as add-on therapy, on clinical response in patients with active, moderate-to-severe, ulcerative colitis

Medical condition

ulcerative colitis

Phase

Phase 2

Healthy volunteers

Study drug

tralokinumab, placebo

Sex

All

Actual Enrollment

147

Study type

Interventional

Age

18 Years - 65 Years

Date

Study Start Date: 01 Mar 2012

Primary Completion Date: 01 Mar 2013

Study Completion Date: 01 Jun 2013

Study design

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

Verification:

Verified 01 Mar 2016 by AstraZeneca

Collaborators

MedImmune Ltd

Inclusion and exclusion criteria

Location

Research Site

Praha 5, Czech Republic

Location

Research Site

Ceske Budejovice, Czech Republic

Location

Research Site

Olomouc, Czech Republic

Location

Research Site

Praha 7, Czech Republic

Location

Research Site

Praha 1, Czech Republic

Location

Research Site

Hradec Kralove, Czech Republic

Location

Research Site

Potsdam, Germany

Location

Research Site

Ludwigshafen, Germany

Arms	Assigned Interventions
Experimental: 1 tralokinumab (CAT-354) sc injection	Drug: tralokinumab 2 sc injections of every 2 weeks for 12 weeks.
Placebo Comparator: 2 placebo sc injection	Drug: placebo 2 sc injections of every 2 weeks for 12 weeks.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
147/111 patients were enrolled/randomized from 31 centres in 6 European countries. The first patient was enrolled on 26 March 2012, and the last patient completed the study on 24 June 2013.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were enrolled for a period of 3 weeks.

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Participant Flow: Overall Study

	Tralokinumab	Placebo
STARTED	56^[1]	55
COMPLETED	43	37
NOT COMPLETED	13	18
Medical decision due to lack of efficacy	0	1
Protocol Violation	1	0
Lost to Follow-up	2	2
Lack of Efficacy	0	1
Adverse Event	2	1
Withdrawal by Subject	8	13

[1]	One participant did not receive study treatment

Baseline Characteristics

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

All randomised participants.

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Baseline Measures

	Tralokinumab	Placebo	Total
Number of Participants [units: Participants]	56	55	111
Age Continuous [units: Years] Mean ± Standard Deviation	42.2 ± 11.54	40.8 ± 13.26	41.5 ± 12.39
Gender, Male/Female [units: Participants]
Female	29	29	58
Male	27	26	53
Race/Ethnicity, Customized [units: Participants]
Asian	2	0	2
White	54	54	108
Other	0	1	1
Race/Ethnicity, Customized [units: Participants]
Hispanic or Latino	2	2	4
Asian (Other than Chinese And Japanese)	2	0	2
Not Applicable	35	40	75
Other	17	13	30
Duration of disease [units: Years] Mean ± Standard Deviation	9.22 ± 8.523	7.78 ± 8.664	8.51 ± 8.585
Mayo score at baseline ^[1] [units: Scores on scale] Mean ( Full Range )	8.36 (5.0 to 11.0)	8.33 (6.0 to 11.0)	8.34 (5.0 to 11.0)
Partial Mayo score at baseline ^[2] [units: Scores on scale] Mean ( Full Range )	5.91 (3.0 to 8.0)	5.85 (3.0 to 8.0)	5.88 (3.0 to 8.0)
Glucocorticosteroid-refractory status ^[3] [units: Participants]
Yes	3	8	11
No	53	46	99
Unknown	0	1	1

Outcome Measures

1. Primary Outcome Measure: Clinical response at week 8 based on Mayo score [ Time Frame: Eight week treatment period ]

Measure Type	Primary
Measure Name	Clinical response at week 8 based on Mayo score
Measure Description	Clinical response was measured as a decrease in Mayo score of ≥3 points from baseline, decrease in the total Mayo score from baseline ≥30 percentage and a decrease in the sub score for rectal bleeding ≥1 or absolute sub score for rectal bleeding of 0 or 1 point. Mayo score is sum of four sub-scores: stool frequency, rectal bleeding, endoscopy findings and the physician’s global assessment. The total Mayo score ranges from 0-12, with higher scores indicating a more severe disease.
Time Frame	Eight week treatment period
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 consist of all randomised participants

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	56	55
Clinical response at week 8 based on Mayo score [units: Percentage of responders]	37.5	32.7

Statistical Analysis 1 for Clinical response at week 8 based on Mayo score

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.4062
Risk Difference (RD)^[5]	4.8
95% Confidence Interval	( -13.0 to 22.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypothesis is that the proportion of participants responding on tralokinumab is less than or equal to the proportion of participants responding on placebo.
[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:
	Glucocorticosteroid-refractory status as stratification factor
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Change in Mayo score from baseline to Week 8 [ Time Frame: Eight week treatment period ]

Measure Type	Secondary
Measure Name	Change in Mayo score from baseline to Week 8
Measure Description	Mayo score is sum of four sub-scores: stool frequency, rectal bleeding, endoscopy findings and the physician’s global assessment. The total Mayo score ranges from 0-12, with higher scores indicating a more severe disease. Change from baseline: Mayo score at week 8 minus the Mayo score at baseline.
Time Frame	Eight week treatment period
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 consist of all randomised participants however the numbers for the endpoints mentioned for this secondary outcome are lower due to missing data.

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	45	42
Change in Mayo score from baseline to Week 8 [units: Score on scale] Least Squares Mean (Standard Error)	-2.41 (0.58)	-1.92 (0.56)

Statistical Analysis 1 for Change in Mayo score from baseline to Week 8

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.3937
Mean Difference (Final Values)^[5]	-0.49
Standard Error of the mean	± 0.57
95% Confidence Interval	( -1.63 to 0.65 )

[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:
	Mayo score at baseline as a covariate, and treatment and glucocorticosteroid-refractory status as factors in the model.
[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: Mucosal healing at week 8 based on Mayo score [ Time Frame: Eight week treatment period ]

Measure Type	Secondary
Measure Name	Mucosal healing at week 8 based on Mayo score
Measure Description	Improvement of the endoscopy sub score (from the Mayo score) from 3 or 2 to 0 or 1 point, or from 1 to 0 points.
Time Frame	Eight week treatment period
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 consist of all randomised participants

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	56	55
Mucosal healing at week 8 based on Mayo score [units: Percentage of participants]	32.1	20.0

Statistical Analysis 1 for Mucosal healing at week 8 based on Mayo score

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.1043
Risk Difference (RD)^[5]	12.1
95% Confidence Interval	( -4.0 to 28.3 )

[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:
	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:
	Glucocorticosteroid-refractory status as stratification factor
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Clinical remission at week 8 based on Mayo score [ Time Frame: Eight week treatment period ]

Measure Type	Secondary
Measure Name	Clinical remission at week 8 based on Mayo score
Measure Description	Participants were classified as in remission if Mayo score of ≤2 with no individual sub score exceeding 1 point. Mayo score is sum of four sub-scores: stool frequency, rectal bleeding, endoscopy findings and the physician’s global assessment. The total Mayo score ranges from 0-12, with higher scores indicating a more severe disease.
Time Frame	Eight week treatment period
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 consist of all randomised participants

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	56	55
Clinical remission at week 8 based on Mayo score [units: Percentage of participants]	17.9	5.5

Statistical Analysis 1 for Clinical remission at week 8 based on Mayo score

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.0326
Risk Difference (RD)^[5]	12.4
95% Confidence Interval	( 0.7 to 24.1 )

[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:
	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:
	Glucocorticosteroid-refractory status as stratification factor
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Change from baseline in partial Mayo score [ Time Frame: From baseline to Week 4, 8, 12, 16, 20, and 24. ]

Measure Type	Secondary
Measure Name	Change from baseline in partial Mayo score
Measure Description	The partial Mayo score is the sum of the three sub-score areas: stool frequency, rectal bleeding, and the physician’s global assessment.The partial Mayo score ranges from 0-9, with higher scores indicating a more severe disease. Change from baseline: Mayo score at each post-baseline timepoint (week 4, 8, 12, 16, 20, and 24) minus the Mayo score at baseline.
Time Frame	From baseline to Week 4, 8, 12, 16, 20, and 24.
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 consist of all randomised participants

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	56	55
Change from baseline in partial Mayo score [units: Score on scale] Mean (Full Range)
Week 4	-1.8 (-8 to 3)	-0.8 (-6 to 4)
Week 8	-2.4 (-6 to 3)	-1.7 (-6 to 1)
Week 12	-2.7 (-7 to 3)	-2.6 (-8 to 4)
Week 16	-2.6 (-7 to 3)	-3.3 (-7 to 2)
Week 20	-3.0 (-7 to 2)	-3.6 (-8 to 1)
Week 24	-3.0 (-7 to 3)	-3.6 (-7 to 1)

No statistical analysis provided for Change from baseline in partial Mayo score

6. Secondary Outcome Measure: Change from baseline in modified Riley score [ Time Frame: Eight week treatment period ]

Measure Type	Secondary
Measure Name	Change from baseline in modified Riley score
Measure Description	Modified Riley score is biopsy grade which range from 0-5; where 0: Normal mucosa, 1: Infiltration of lymphocytes and plasma cells in the lamina propria, 2: Infiltration of neutrophils and eosinophils in the lamina propria, 3: Infiltration of neutrophils in the epithelium, 4: Crypt destruction, 5: Erosion and/or ulceration.
Time Frame	Eight week treatment period
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 consist of all randomised participants however the numbers for the endpoints mentioned for this secondary outcome are lower due to missing data.

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	37	35
Change from baseline in modified Riley score [units: Grade on scale] Least Squares Mean (Standard Error)	-0.49 (0.23)	-0.74 (0.24)

Statistical Analysis 1 for Change from baseline in modified Riley score

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.4490
Mean Difference (Final Values)^[5]	0.25
Standard Error of the mean	± 0.33
95% Confidence Interval	( -0.41 to 0.91 )

[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:
	Modified Riley score at baseline as a covariate, and treatment as factors in the model.
[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.

7. Secondary Outcome Measure: Change from baseline in C - reactive protein [ Time Frame: From baseline to Week 4, 8, 12, 16, 20, and 24. ]

Measure Type	Secondary
Measure Name	Change from baseline in C - reactive protein
Measure Description
Time Frame	From baseline to Week 4, 8, 12, 16, 20, and 24.
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 consist of all randomised participants

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	56	55
Change from baseline in C - reactive protein [units: mg/L] Mean (Full Range)
Week 4	-2.755 (-33.00 to 25.00)	0.510 (-12.00 to 32.00)
Week 8	-1.089 (-29.00 to 29.00)	0.637 (-43.00 to 46.00)
Week 12	-2.795 (-46.00 to 63.00)	-1.974 (-61.00 to 43.00)
Week 16	-3.490 (-53.00 to 19.00)	0.638 (-61.00 to 97.00)
Week 20	-4.094 (-52.00 to 43.00)	-1.467 (-62.00 to 31.00)
Week 24	-2.754 (-36.00 to 25.00)	-1.915 (-59.00 to 36.00)

No statistical analysis provided for Change from baseline in C - reactive protein

8. Secondary Outcome Measure: Change from baseline in Albumin [ Time Frame: From baseline to Week 4, 8, 12, 16, 20, and 24. ]

Measure Type	Secondary
Measure Name	Change from baseline in Albumin
Measure Description
Time Frame	From baseline to Week 4, 8, 12, 16, 20, and 24.
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 consist of all randomised participants

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	56	55
Change from baseline in Albumin [units: g/L] Mean (Full Range)
Week 4	0.0 (-8 to 5)	-0.7 (-7 to 6)
Week 8	0.8 (-7 to 8)	-0.2 (-8 to 5)
Week 12	0.3 (-9 to 5)	-0.4 (-8 to 5)
Week 16	0.5 (-10 to 12)	0.4 (-7 to 7)
Week 20	1.1 (-4 to 7)	0.1 (-6 to 9)
Week 24	1.2 (-4 to 8)	0.2 (-6 to 8)

No statistical analysis provided for Change from baseline in Albumin

9. Secondary Outcome Measure: Change from baseline in Calprotectin [ Time Frame: From baseline to Week 4, 8, 12, 16, 20, and 24. ]

Measure Type	Secondary
Measure Name	Change from baseline in Calprotectin
Measure Description
Time Frame	From baseline to Week 4, 8, 12, 16, 20, and 24.
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 consist of all randomised participants

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	56	55
Change from baseline in Calprotectin [units: ug/g] Mean (Full Range)
Week 4	69.45 (-1068.0 to 931.0)	198.80 (-1315.0 to 4188.0)
Week 8	86.47 (-894.2 to 912.0)	-250.52 (-4005.0 to 4505.0)
Week 12	-39.19 (-1109.0 to 841.0)	50.31 (-1234.0 to 4811.0)
Week 16	-75.10 (-1008.0 to 1056.0)	-338.76 (-3857.0 to 1138.0)
Week 20	32.55 (-1155.0 to 4669.0)	-402.81 (-3835.0 to 794.0)
Week 24	-136.78 (-1120.0 to 617.0)	-267.58 (-1172.0 to 824.0)

No statistical analysis provided for Change from baseline in Calprotectin

10. Secondary Outcome Measure: Serum concentration of Tralokinumab [ Time Frame: Pre-dose sampling at baseline, Week 4, 8, 12, 16, 20, and 24. ]

Measure Type	Secondary
Measure Name	Serum concentration of Tralokinumab
Measure Description
Time Frame	Pre-dose sampling at baseline, Week 4, 8, 12, 16, 20, and 24.
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 safety analysis set consist of all randomised participants who received at least one dose of study medication.

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	55	55
Serum concentration of Tralokinumab [units: ug/ml] Mean (Full Range)
pre-dose at baseline	0.00 (0.000 to 0.000)	NA (NA to NA) ^[1]
Week 4	37.9 (12.2 to 92.2)	NA (NA to NA) ^[2]
Week 8	50.2 (5.83 to 116)	NA (NA to NA) ^[3]
Week 12	48.2 (0.781 to 109)	NA (NA to NA) ^[4]
Week 16	27.2 (0.369 to 82.7)	NA (NA to NA) ^[5]
Week 20	9.32 (0.527 to 36.9)	NA (NA to NA) ^[6]
Week 24	3.66 (0.000 to 18.0)	NA (NA to NA) ^[7]

[1]	Not calculable because below the lower limit of quantification
[2]	Not calculable because below the lower limit of quantification
[3]	Not calculable because below the lower limit of quantification
[4]	There are only two concentration results available for Placebo Patients specified in the listing: Day 85 - 0,658 - below LLOQ Day 89 - 5.93 - above LLOQ
[5]	Not calculable because below the lower limit of quantification
[6]	Not calculable because below the lower limit of quantification
[7]	Not calculable because below the lower limit of quantification

No statistical analysis provided for Serum concentration of Tralokinumab

11. Secondary Outcome Measure: Immunogenicity [ Time Frame: Pre-dose sampling at baseline, Week 8, 12, 16, and 24. ]

Measure Type	Secondary
Measure Name	Immunogenicity
Measure Description	Incidence of anti-drug antibodies (ADA) to tralokinumab in serum.
Time Frame	Pre-dose sampling at baseline, Week 8, 12, 16, and 24.
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 safety analysis set consist of all randomised participants who received at least one dose of study medication.

Reporting Groups

	Description
Tralokinumab	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.

Measured Values

	Tralokinumab	Placebo
Number of Participants Analyzed [units:participants]	55	55
Immunogenicity [units: participants]
pre-dose at baseline	0	1
Week 8	0	1
Week 12	0	1
Week 16	0	1
Week 24	0	0

No statistical analysis provided for Immunogenicity

Serious Adverse Events

Time Frame	24 Weeks
Additional Description	No text entered.

Reporting Groups

	Description
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.
Tralokinumab 300 mg	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.

Serious Adverse Events

Placebo

Tralokinumab 300 mg

Total, serious adverse events

# participants affected / at risk

6/55 (10.91%)

7/55 (12.73%)

BLOOD AND LYMPHATIC SYSTEM DISORDERS

ANAEMIA¹,^†

# participants affected / at risk

1/55 (1.82%)

# events

GASTROINTESTINAL DISORDERS

COLITIS ULCERATIVE¹,^†

# participants affected / at risk

5/55 (9.09%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

GENERAL PHYSICAL HEALTH DETERIORATION¹,^†

# participants affected / at risk

1/55 (1.82%)

0/55 (0.00%)

# events

IMMUNE SYSTEM DISORDERS

SERUM SICKNESS¹,^†

# participants affected / at risk

0/55 (0.00%)

1/55 (1.82%)

# events

NERVOUS SYSTEM DISORDERS

CEREBROVASCULAR ACCIDENT¹,^†

# participants affected / at risk

1/55 (1.82%)

0/55 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 16.0

Other Adverse Events

Time Frame	24 Weeks
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	2%

Reporting Groups

	Description
Placebo	Placebo was administered during study as two subcutaneous injections every 2 weeks for 12 weeks starting from Visit 2.
Tralokinumab 300 mg	Tralokinumab 300 mg was administered during study as two subcutaneous 150 mg injections every 2 weeks for 12 weeks starting from Visit 2.

Other Adverse Events

Placebo

Tralokinumab 300 mg

Total, other (not including serious) adverse events

# participants affected / at risk

35/55 (63.64%)

36/55 (65.45%)

BLOOD AND LYMPHATIC SYSTEM DISORDERS

ANAEMIA¹,^†

# participants affected / at risk

1/55 (1.82%)

3/55 (5.45%)

# events

GASTROINTESTINAL DISORDERS

ABDOMINAL PAIN¹,^†

# participants affected / at risk

6/55 (10.91%)

7/55 (12.73%)

# events

GASTROINTESTINAL DISORDERS

COLITIS ULCERATIVE¹,^†

# participants affected / at risk

10/55 (18.18%)

11/55 (20.00%)

# events

GASTROINTESTINAL DISORDERS

HAEMORRHOIDS¹,^†

# participants affected / at risk

1/55 (1.82%)

3/55 (5.45%)

# events

GASTROINTESTINAL DISORDERS

TOOTHACHE¹,^†

# participants affected / at risk

1/55 (1.82%)

3/55 (5.45%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

ASTHENIA¹,^†

# participants affected / at risk

5/55 (9.09%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

FATIGUE¹,^†

# participants affected / at risk

2/55 (3.64%)

3/55 (5.45%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

INJECTION SITE ERYTHEMA¹,^†

# participants affected / at risk

0/55 (0.00%)

3/55 (5.45%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

INJECTION SITE REACTION¹,^†

# participants affected / at risk

0/55 (0.00%)

3/55 (5.45%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

PYREXIA¹,^†

# participants affected / at risk

4/55 (7.27%)

6/55 (10.91%)

# events

INFECTIONS AND INFESTATIONS

INFLUENZA¹,^†

# participants affected / at risk

4/55 (7.27%)

2/55 (3.64%)

# events

INFECTIONS AND INFESTATIONS

NASOPHARYNGITIS¹,^†

# participants affected / at risk

5/55 (9.09%)

3/55 (5.45%)

# events

INVESTIGATIONS

WEIGHT DECREASED¹,^†

# participants affected / at risk

0/55 (0.00%)

3/55 (5.45%)

# events

METABOLISM AND NUTRITION DISORDERS

DECREASED APPETITE¹,^†

# participants affected / at risk

0/55 (0.00%)

3/55 (5.45%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

ARTHRALGIA¹,^†

# participants affected / at risk

7/55 (12.73%)

3/55 (5.45%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

BACK PAIN¹,^†

# participants affected / at risk

4/55 (7.27%)

3/55 (5.45%)

# events

NERVOUS SYSTEM DISORDERS

HEADACHE¹,^†

# participants affected / at risk

12/55 (21.82%)

10/55 (18.18%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

DYSPNOEA¹,^†

# participants affected / at risk

0/55 (0.00%)

3/55 (5.45%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

OROPHARYNGEAL PAIN¹,^†

# participants affected / at risk

2/55 (3.64%)

4/55 (7.27%)

# events

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

ALOPECIA¹,^†

# participants affected / at risk

2/55 (3.64%)

3/55 (5.45%)

# events

CARDIAC DISORDERS

TACHYCARDIA¹,^†

# participants affected / at risk

2/55 (3.64%)

# events

GASTROINTESTINAL DISORDERS

ABDOMINAL DISCOMFORT¹,^†

# participants affected / at risk

0/55 (0.00%)

2/55 (3.64%)

# events

GASTROINTESTINAL DISORDERS

ABDOMINAL TENDERNESS¹,^†

# participants affected / at risk

1/55 (1.82%)

2/55 (3.64%)

# events

GASTROINTESTINAL DISORDERS

DIARRHOEA¹,^†

# participants affected / at risk

0/55 (0.00%)

2/55 (3.64%)

# events

GASTROINTESTINAL DISORDERS

DYSPEPSIA¹,^†

# participants affected / at risk

2/55 (3.64%)

# events

GASTROINTESTINAL DISORDERS

NAUSEA¹,^†

# participants affected / at risk

2/55 (3.64%)

# events

GASTROINTESTINAL DISORDERS

VOMITING¹,^†

# participants affected / at risk

2/55 (3.64%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

INFLUENZA LIKE ILLNESS¹,^†

# participants affected / at risk

2/55 (3.64%)

0/55 (0.00%)

# events

INFECTIONS AND INFESTATIONS

PHARYNGITIS¹,^†

# participants affected / at risk

2/55 (3.64%)

# events

INFECTIONS AND INFESTATIONS

SINUSITIS¹,^†

# participants affected / at risk

2/55 (3.64%)

1/55 (1.82%)

# events

METABOLISM AND NUTRITION DISORDERS

VITAMIN D DEFICIENCY¹,^†

# participants affected / at risk

2/55 (3.64%)

0/55 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

MUSCLE SPASMS¹,^†

# participants affected / at risk

2/55 (3.64%)

0/55 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

MYALGIA¹,^†

# participants affected / at risk

2/55 (3.64%)

1/55 (1.82%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

PAIN IN EXTREMITY¹,^†

# participants affected / at risk

2/55 (3.64%)

1/55 (1.82%)

# events

NERVOUS SYSTEM DISORDERS

DIZZINESS¹,^†

# participants affected / at risk

2/55 (3.64%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

COUGH¹,^†

# participants affected / at risk

2/55 (3.64%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 16.0

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:

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:	Mark Berner Hansen
Organization:	AstraZeneca
Phone	+46 31 776 4794
E-mail:	[email protected]

Documents available

D2211C00001_Protocol_Redacted
Download
D2211C00001_Study_Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Mark Berner Hansen

AstraZeneca R&D Mölndal Pepparedsleden 1, S-431 83 Mölndal, Sweden

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

D2211C00001_Protocol_Redacted

D2211C00001_Study_Synopsis

Trial Results Summaries