A Study to Evaluate the Safety of Tralokinumab in Adults and Adolescents with Uncontrolled Asthma

Study identifier:D2210C00029

ClinicalTrials.gov identifier:NCT02902809

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A 52-Week, Open-Label, Multicentre Study to Evaluate the Safety of Tralokinumab in Japanese Adults and Adolescents with Asthma Inadequately Controlled on Inhaled Corticosteroid plus Long-Acting β2-Agonist

Medical condition

Inadequately Controlled Asthma

Phase

Phase 3

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

12 Years - 75 Years

Date

Study Start Date: 11 Nov 2016

Primary Completion Date: 19 Jan 2018

Study Completion Date: 19 Jan 2018

Study design

Allocation: N/A
Endpoint Classification: Safety
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2019 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Itabashi-ku, Japan, 173-8610

Location

Research Site

Chuo-ku, Japan, 103-0027

Location

Research Site

Yokohama-shi, Japan, 236-0004

Arms	Assigned Interventions
Experimental: Open-label study to evaluate safety A fixed 300 mg dose every 2 weeks (Q2W) of tralokinumab administered subcutaneously in subjects with inadequately controlled asthma on medium to high-dose of inhaled corticosteroid plus long-acting β2-agonist.	Biological/Vaccine: Tralokinumab open-label Subcutaneous injection; fixed dose; 300 mg Other Name: Tralokinumab

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Adult participants with asthma inadequately controlled on inhaled corticosteroid plus long-acting beta 2 agonist were recruited at 4 sites in Japan from 01 November 2016 until study termination on 24 January 2018. No adolescent participants were enrolled in the study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of all enrolled participants, 3 were considered screen failures and 28 participants were received study treatment. Following initial screening, there was a run-in period of up to 2 weeks to allow adequate time for eligibility criteria to be evaluated prior to entry to planned 52-week treatment period followed by a 14 week extended follow-up period.

Reporting Groups

	Description
Tralokinumab 300 mg Every 2 Weeks (Q2W)	Participants were administered with tralokinumab 300 milligram (mg) subcutaneous injection every 2 weeks for 52 weeks.

Participant Flow: Overall Study

	Tralokinumab 300 mg Every 2 Weeks (Q2W)
STARTED	28
Treatment Received	28
Treatment Completed	2
COMPLETED	0
NOT COMPLETED	28
Discontinuation of asthma program	28

Baseline Characteristics

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

The safety analysis set included all participants enrolled and who received at least 1 dose of investigational product irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Tralokinumab 300 mg Every 2 Weeks (Q2W)	Participants were administered with tralokinumab 300 mg subcutaneous injection every 2 weeks for 52 weeks.

Baseline Measures

	Tralokinumab 300 mg Every 2 Weeks (Q2W)
Number of Participants [units: Participants]	28
Age Continuous [units: Years] Mean ± Standard Deviation	47.7 ± 10.8
Age Categorical [units: Participants]
<=18 years	0
Between 18 and 65 years	27
>=65 years	1
Sex: Female, Male [units: Participants]
Female	15
Male	13
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0
Asian	28
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	0
More than one race	0
Unknown or Not Reported	0
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	0
Not Hispanic or Latino	28
Unknown or Not Reported	0

Outcome Measures

1. Primary Outcome Measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From Screening (Day -14) up to 14 weeks after end of treatment (Week 66). ]

Measure Type	Primary
Measure Name	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measure Description	An AE was development of an undesirable medical condition or deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to product. An undesirable medical condition can be symptoms, signs or the abnormal results of an investigation. In clinical studies, an AE can include an undesirable medical condition occurring at any time, including run-in or washout periods, even if no study treatment has been administered. A SAE was an AE occurred during any study phase that fulfils one or more of the following criteria: death; immediately life-threatening, in-patient or prolongation of existing hospitalization; persistent or significant disability/incapacity or substantial disruption of ability to conduct normal life functions; congenital abnormality or birth defect; important medical event that may jeopardise participant or may require medical intervention to prevent one of the outcomes listed above.
Time Frame	From Screening (Day -14) up to 14 weeks after end of treatment (Week 66).
Safety Issue?	Yes

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 included all participants enrolled and who received at least 1 dose of investigational product irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Tralokinumab 300 mg Every 2 Weeks (Q2W)	Participants were administered with tralokinumab 300 mg subcutaneous injection every 2 weeks for 52 weeks.

Measured Values

	Tralokinumab 300 mg Every 2 Weeks (Q2W)
Number of Participants Analyzed [units:participants]	28
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [units: Participants]
Any AE	21
Any AE with outcome of death	0
Any SAE (including events with outcome of death)	1
Any AE leading to discontinuation of study drug	1

No statistical analysis provided for Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

2. Primary Outcome Measure: Number of Participants With Clinical Laboratory Abnormalities [ Time Frame: From Screening (Day -14) up to 14 weeks after end of treatment (Week 66). ]

Measure Type	Primary
Measure Name	Number of Participants With Clinical Laboratory Abnormalities
Measure Description	Blood and urine samples for determination of clinical chemistry, haematology and urinalysis parameters were taken at the times. Changes in haematology and clinical chemistry variables between baseline and each subsequent scheduled assessment were evaluated. Baseline is defined as the last available value measured prior to the first dose of study treatment. The change from baseline is defined as the treatment period value minus the baseline period value. Absolute values were compared to the relevant reference range and classified as low (below range), normal (within range or on limits) or high (above range). The AstraZeneca extended reference ranges were used for laboratory variables (where they exist). All values (absolute and change) falling outside the reference ranges were flagged. Urinalysis data were categorised as negative (0), trace or positive (+) at each time point.
Time Frame	From Screening (Day -14) up to 14 weeks after end of treatment (Week 66).
Safety Issue?	Yes

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.
No participants were analysed as the study was terminated due to discontinuation of tralokinumab asthma program. Study was reported in a synopsis format. Individual listings of clinical laboratory parameters were evaluated for safety signal.

Reporting Groups

	Description
Tralokinumab 300 mg Every 2 Weeks (Q2W)	Participants were administered with tralokinumab 300 mg subcutaneous injection every 2 weeks for 52 weeks.

Measured Values

	Tralokinumab 300 mg Every 2 Weeks (Q2W)
Number of Participants Analyzed [units:participants]	0
Number of Participants With Clinical Laboratory Abnormalities [units: Participants]	0

No statistical analysis provided for Number of Participants With Clinical Laboratory Abnormalities

3. Primary Outcome Measure: Number of Participants With Abnormal Physical Examinations [ Time Frame: From Screening (Day -14) up to 14 weeks after end of treatment (Week 66). ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Physical Examinations
Measure Description	Physical examination included assessment of general appearance, skin, head and neck (including eyes, ears, nose, mouth and throat), lymph nodes, abdomen, musculoskeletal (including spine and extremities), cardiovascular, respiratory, and neurological systems. Criteria for abnormal physical findings were based on investigator's discretion.
Time Frame	From Screening (Day -14) up to 14 weeks after end of treatment (Week 66).
Safety Issue?	Yes

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 study was terminated due to discontinuation of tralokinumab asthma program. Study was reported in a synopsis format. Individual listings were evaluated for safety signal. Any new finding(s) or aggravated existing finding(s), judged as clinically significant by the Investigator, were reported as an AE.

Reporting Groups

	Description
Tralokinumab 300 mg Every 2 Weeks (Q2W)	Participants were administered with tralokinumab 300 mg subcutaneous injection every 2 weeks for 52 weeks.

Measured Values

	Tralokinumab 300 mg Every 2 Weeks (Q2W)
Number of Participants Analyzed [units:participants]	0
Number of Participants With Abnormal Physical Examinations [units: Participants]

No statistical analysis provided for Number of Participants With Abnormal Physical Examinations

4. Primary Outcome Measure: Number of Participants With Vital Signs Abnormalities [ Time Frame: From Screening (Day -14) up to 14 weeks after end of treatment (Week 66). ]

Measure Type	Primary
Measure Name	Number of Participants With Vital Signs Abnormalities
Measure Description	Vital signs that were planned to be assessed included parameters such as pulse, systolic blood pressure, diastolic blood pressure, respiration rate and body temperature.
Time Frame	From Screening (Day -14) up to 14 weeks after end of treatment (Week 66).
Safety Issue?	Yes

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 study was terminated due to discontinuation of tralokinumab asthma program. Study was reported in a synopsis format. Individual listings were evaluated for safety signal. No summary table was developed.

Reporting Groups

	Description
Tralokinumab 300 mg Every 2 Weeks (Q2W)	Participants were administered with tralokinumab 300 mg subcutaneous injection every 2 weeks for 52 weeks.

Measured Values

	Tralokinumab 300 mg Every 2 Weeks (Q2W)
Number of Participants Analyzed [units:participants]	0
Number of Participants With Vital Signs Abnormalities [units: Participants]

No statistical analysis provided for Number of Participants With Vital Signs Abnormalities

5. Primary Outcome Measure: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities [ Time Frame: At Day -14 and Week 52. ]

Measure Type	Primary
Measure Name	Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
Measure Description	The ECG assessments were performed using an ECG device prior to blood drawing, spirometry, investigational product administration and bronchodilator administration. ECG data and evaluation was planned to be performed by the site Investigator.
Time Frame	At Day -14 and Week 52.
Safety Issue?	Yes

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 study was terminated due to discontinuation of tralokinumab asthma program. Study was reported in a synopsis format. Individual listings were evaluated for safety signal. No summary table was developed.

Reporting Groups

	Description
Tralokinumab 300 mg Every 2 Weeks (Q2W)	Participants were administered with tralokinumab 300 mg subcutaneous injection every 2 weeks for 52 weeks.

Measured Values

	Tralokinumab 300 mg Every 2 Weeks (Q2W)
Number of Participants Analyzed [units:participants]	0
Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities [units: Participants]

No statistical analysis provided for Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities

Serious Adverse Events

Time Frame	From Screening (Day -14) to study termination (Approximately 60 weeks).
Additional Description	The safety analysis set included all participants enrolled and who received at least 1 dose of investigational product irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Tralokinumab 300 mg Every 2 Weeks (Q2W)	Participants were administered with tralokinumab 300 mg subcutaneous injection every 2 weeks for 52 weeks.

Serious Adverse Events

Tralokinumab 300 mg Every 2 Weeks (Q2W)

Total, serious adverse events

# participants affected / at risk

1/28 (3.57%)

Infections and infestations

Chronic tonsillitis¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 20.0

Other Adverse Events

Time Frame	From Screening (Day -14) to study termination (Approximately 60 weeks).
Additional Description	The safety analysis set included all participants enrolled and who received at least 1 dose of investigational product irrespective of their protocol adherence and continued participation in the study.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Tralokinumab 300 mg Every 2 Weeks (Q2W)	Participants were administered with tralokinumab 300 mg subcutaneous injection every 2 weeks for 52 weeks.

Other Adverse Events

Tralokinumab 300 mg Every 2 Weeks (Q2W)

Total, other (not including serious) adverse events

# participants affected / at risk

21/28 (75.00%)

Infections and infestations

Viral upper respiratory tract infection¹,^†

# participants affected / at risk

10/28 (35.71%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

4/28 (14.29%)

# events

Infections and infestations

Oral herpes¹,^†

# participants affected / at risk

2/28 (7.14%)

# events

Infections and infestations

Acute sinusitis¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Infections and infestations

Cystitis¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Infections and infestations

Oral candidiasis¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Infections and infestations

Otitis media acute¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Infections and infestations

Tonsillitis¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

3/28 (10.71%)

# events

Nervous system disorders

Sciatica¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Nervous system disorders

Tremor¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Eye disorders

Dry eye¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Cardiac disorders

Palpitations¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Vascular disorders

Hyperaemia¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

3/28 (10.71%)

# events

Respiratory, thoracic and mediastinal disorders

Upper respiratory tract inflammation¹,^†

# participants affected / at risk

3/28 (10.71%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

2/28 (7.14%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

2/28 (7.14%)

# events

Gastrointestinal disorders

Cheilitis¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Hepatobiliary disorders

Hepatic function abnormal¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Skin and subcutaneous tissue disorders

Dermatitis allergic¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Skin and subcutaneous tissue disorders

Dermatitis contact¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Skin and subcutaneous tissue disorders

Ingrowing nail¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Skin and subcutaneous tissue disorders

Urticaria¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

General disorders

Injection site reaction¹,^†

# participants affected / at risk

9/28 (32.14%)

# events

General disorders

Asthenia¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

General disorders

Injection site pain¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

General disorders

Injection site swelling¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

General disorders

Pyrexia¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

General disorders

Thirst¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

1/28 (3.57%)

# events

Injury, poisoning and procedural complications

Contusion¹,^†

# participants affected / at risk

2/28 (7.14%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 20.0

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
Study was terminated due to discontinuation of tralokinumab asthma program. Study was reported in a synopsis format. Individual listings of laboratory variables, physical examinations, vitals and ECG were evaluated for safety signal.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	+1 301-398-0582
E-mail:	[email protected]

Documents available

Statistical Analysis Plan
Download
Clinical Study Protocol
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Takeshi Kaneko

Yokohama City University Graduate School of Medicine

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Statistical Analysis Plan

Clinical Study Protocol

Trial Results Summaries