A Safety and Efficacy Study of Tralokinumab in Adults With Asthma

A Phase 2b, Randomized, Double-blind Study to Evaluate the Efficacy of Tralokinumab in Adults With Uncontrolled, Severe Asthma

The purpose of this study is to determine whether the addition of tralokinumab to standard asthma medication is effective in the treatment of adults with asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Other: Placebo Q2W; Biological: Tralokinumab 300 mg, Q2W; Other: Placebo, Q2/4W; Biological: Tralokinumab 300 mg, Q2/4W

Detailed Description

Interleukin-13 (IL-13) is a key mediator in the pathogenesis of established asthmatic disease. Tralokinumab is a human monoclonal antibody that blocks IL-13, which may result in improved control of asthma. This study will determine whether the addition of tralokinumab to standard asthma medications results in a reduced rate of asthma exacerbations in subjects with severe asthma.

• Study Type: Interventional
• Enrollment (Actual): 689
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Research Site
  • Ciudad de Buenos Aires, Argentina
    • Research Site
  • Monte Grande, Argentina
    • Research Site
  • Ranelagh, Argentina
    • Research Site
  • Rosario, Argentina
    • Research Site
• Canada
  • Quebec, Canada
    • Research Site
  • Alberta
    • Calgary, Alberta, Canada
      • Research Site
  • Ontario
    • Ottawa, Ontario, Canada
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada
      • Research Site
• Chile
  • Quillota, Chile
    • Research Site
  • Santiago, Chile
    • Research Site
  • Valparaiso, Chile
    • Research Site
  • Viña del Mar, Chile
    • Research Site
• Czech Republic
  • Jindrichuv Hradec, Czech Republic
    • Research Site
  • Plzen, Czech Republic
    • Research Site
  • Rokycany, Czech Republic
    • Research Site
• France
  • Marseille Cedex 20, France
    • Research Site
  • Montpellier, France
    • Research Site
  • Nantes Cedex 1, France
    • Research Site
  • Paris Cedex 18, France
    • Research Site
  • Perpignan, France
    • Research Site
  • Pessac, France
    • Research Site
  • Strasbourg Cedex, France
    • Research Site
• Germany
  • Berlin, Germany
    • Research Site
  • Frankfurt, Germany
    • Research Site
  • Lübeck, Germany
    • Research Site
  • Mainz, Germany
    • Research Site
• Japan
  • Chuo-ku, Japan
    • Research Site
  • Fujisawa-shi, Japan
    • Research Site
  • Fukuoka-shi, Japan
    • Research Site
  • Habikino-shi, Japan
    • Research Site
  • Hiroshima-shi, Japan
    • Research Site
  • Itabashi-ku, Japan
    • Research Site
  • Kagoshima-shi, Japan
    • Research Site
  • Kahoku-gun, Japan
    • Research Site
  • Kishiwada-shi, Japan
    • Research Site
  • Kobe-shi, Japan
    • Research Site
  • Kyoto-shi, Japan
    • Research Site
  • Maebashi-shi, Japan
    • Research Site
  • Morioka-shi, Japan
    • Research Site
  • Naka-gun, Japan
    • Research Site
  • Sagamihara-shi, Japan
    • Research Site
  • Sakaide-shi, Japan
    • Research Site
  • Sapporo-shi, Japan
    • Research Site
  • Sumida-ku, Japan
    • Research Site
  • Takatsuki-shi, Japan
    • Research Site
  • Tomakomai-shi, Japan
    • Research Site
  • Wakayama-shi, Japan
    • Research Site
  • Yokohama-shi, Japan
    • Research Site
• Korea, Republic of
  • Bucheon-si, Korea, Republic of
    • Research Site
  • Incheon, Korea, Republic of
    • Research Site
  • Seoul, Korea, Republic of
    • Research Site
  • Suwon-si, Korea, Republic of
    • Research Site
• Mexico
  • Culiacan, Mexico
    • Research Site
  • Guadalajara, Mexico
    • Research Site
  • Morelia, Mexico
    • Research Site
  • México, Mexico
    • Research Site
  • Santiago de Querétaro, Mexico
    • Research Site
  • Tampico, Mexico
    • Research Site
  • Villahermosa, Mexico
    • Research Site
• Philippines
  • Iloilo City, Philippines
    • Research Site
  • Lipa City, Philippines
    • Research Site
  • Quezon City, Philippines
    • Research Site
• Poland
  • Wrocław, Poland
    • Research Site
  • Zabrze, Poland
    • Research Site
  • Łódź, Poland
    • Research Site
• Russian Federation
  • Ekaterinburg, Russian Federation
    • Research Site
  • Moscow, Russian Federation
    • Research Site
  • Novosibirsk, Russian Federation
    • Research Site
  • Saint Petersburg, Russian Federation
    • Research Site
  • Vladikavkaz, Russian Federation
    • Research Site
  • Yekaterinburg, Russian Federation
    • Research Site
• Spain
  • Barcelona, Spain
    • Research Site
  • Madrid, Spain
    • Research Site
  • Pamplona, Spain
    • Research Site
  • Sagunto(Valencia), Spain
    • Research Site
  • Santander, Spain
    • Research Site
• United Kingdom
  • Leicester, United Kingdom
    • Research Site
  • Manchester, United Kingdom
    • Research Site
• United States
  • California
    • Rancho Mirage, California, United States
      • Research Site
  • Colorado
    • Centennial, Colorado, United States
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States
      • Research Site
  • Florida
    • Cocoa, Florida, United States
      • Research Site
    • Miami, Florida, United States
      • Research Site
    • Winter Park, Florida, United States
      • Research Site
  • Georgia
    • Albany, Georgia, United States
      • Research Site
  • North Dakota
    • Fargo, North Dakota, United States
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Research Site
    • Upland, Pennsylvania, United States
      • Research Site
  • Texas
    • Killeen, Texas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-75 years
• Body mass index (BMI) between 16-40 kilogram per square meter (kg/m^2) at Visit 1
• Uncontrolled severe asthma
• A chest x-ray with no abnormality
• Females of childbearing potential who are sexually active with a non-sterilized male partner must use highly effective contraception from Day 1
• Non-sterilized males or sterilized males who are less than or equal to (=<) 1 year post-vasectomy who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception

Exclusion Criteria:

• Employee of the clinical study site or any other individuals directly involved with the conduct of the study, or immediate family members of such individuals
• Pregnant or breastfeeding women
• Any other respiratory disease
• Previously taken tralokinumab (the study drug)
• Current smoker or a history of smoking which would be more than 1 pack per day for 10 years
• Known immune deficiency
• History of cancer
• Hepatitis B, C or Human Immuno-deficiency Virus (HIV)
• Any disease which may cause complications whilst taking the study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo, Q2W - Cohort 1; Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.	Other: Placebo Q2W; Participants who received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.
Experimental: Tralokinumab 300 mg, Q2W - Cohort 1; Participants received tralokinumab 300 milligram (mg) subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.	Biological: Tralokinumab 300 mg, Q2W; Participants received tralokinumab 300 mg subcutaneous injection Q2W for a total of 26 doses up to 50 weeks.; Other Names: CAT-354
Placebo Comparator: Placebo, Q2/4W - Cohort 2; Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.	Other: Placebo, Q2/4W; Participants received matching placebo subcutaneous injection Q2W for 12 weeks followed by Q4W for 38 weeks (Q2/4W) for a total of 16 doses.
Experimental: Tralokinumab 300 mg, Q2/4W - Cohort 2; Participants received tralokinumab 300 mg subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.	Biological: Tralokinumab 300 mg, Q2/4W; Participants received tralokinumab 300 mg subcutaneous injection Q2W for 12 weeks followed by Q4W for 38 weeks (Q2/4W) for a total of 16 doses.; Other Names: CAT-354

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual Asthma Exacerbation Rate (AER)	Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed or administered by the investigator or healthcare provider; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. An asthma exacerbation event was considered resolved 7 days after the last dose of oral corticosteroids (OCS) is administered (10 days after administration of an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53	Pre- and post-bronchodilator FEV1 at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Baseline and Week 53
Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53	Pre- and post-bronchodilator FEV6 at clinic visits (morning) were measured. FEV6 was the maximal volume of air exhaled in the six second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Baseline and Week 53
Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53	Pre- and post-bronchodilator FVC at clinic visits (morning) were measured. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Baseline and Week 53
Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53	Pre- and post-bronchodilator FEV1 and FVC at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Ratio of FEV1/FVC was analysed. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Baseline and Week 53
Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53	Pre- and post-bronchodilator IC at clinic visits (morning) were measured. IC was measured by spirometry. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Baseline and Week 53
Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home	Pre- and post-bronchodilator FEV1 at home (morning and evening) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home	The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at home (morning and evening) while sitting or standing prior to using any medication (if needed) for asthma. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53	Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Baseline and Week 53
Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53	AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Baseline and Week 53
Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53	The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The health state valuation was the summary score of mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a 3 category scale (no problem, moderate problem, severe problems) that reflects increasing levels of difficulty. The minimum possible value is 5 (one point for each dimension) and the maximum possible values is 15 (3 points for each dimension). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 53
Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Week 53	The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The EQ-5D VAS was measured from 0 (worst imaginable health state) to 100 (best imaginable health state). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Baseline and Week 53
Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53	There were 3 symptom questions in the ASMA diary: daytime frequency (question 1), daytime severity (question 2) and nighttime severity (question 6). All symptom questions were scored from 0 to 4 averaged, where a higher score indicated greater frequency or severity. Daily Asthma symptom scores were averaged weekly for participants with at least 4 non-missing records each week. The baseline score was calculated from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
Change From Baseline in Rescue Medication Use at Week 53	Rescue medication use was collected from 3 questions: daytime use in response to symptoms (question 3), daytime prophylactic use (question 4) and nighttime use (question 7). Rescue medication use questions were first assessed using a dichotomous response option (YES/NO). If the participants reported YES, there was a subsequent question about the number of times rescue medication was used (questions 3a, 4a, and 7a). Daily average scores were summarized each week for all participants with at least 4 non-missing records each week. Days with no reported rescue medication use were represented as 0 and included in the calculation with participants who reported yes and completed questions 3a, 4a and 7a. The baseline scores were calculated from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and up to Week 75 that were absent before treatment or that worsened relative to pre-treatment state. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Baseline and Week 75
Observed Serum Tralokinumab Concentration at Week 53	Tralokinumab concentrations that were below limit of quantification (LOQ) of the pharmacokinetic (PK) assay (LOQ = 0.500 microgram per milliliter [mcg/mL]) were replaced by LOQ/2 = 0.250 mcg/mL; results were reported to 3 significant figures level of precision. Observed serum tralokinumab concentration at Week 53 was reported.	Week 53
Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab	Immunogenicity assessment included determination of anti-drug (tralokinumab) antibodies in serum samples. ADA positive was defined as a titer greater than or equal to (>=13) at any point in the study. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Baseline and Week 75
Severe Annual Asthma Exacerbation Rate (AER)	Severe annualized AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed or administered by the investigator; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. An asthma exacerbation event was considered resolved 7 days after the last dose of oral corticosteroids is administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Time to First Exacerbation Through Week 53	Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Time to First Severe Exacerbation Through Week 53	Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin	Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER was evaluated by subgroup baseline serum periostin greater than or equal to (>=) or less than (<) median, >= or < 25th percentile and >= or < 75th percentile. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status	Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. AER was evaluated by subgroup Th2 status. Th2-high included those participants who had immunoglobulin E (IgE) >100 international unit per milliliter (IU/mL) and blood eosinophils >= 0.14 * 10 power 9 per Liter. Th2 low would include those participants who do not meet Th2 high status. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count	Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroups baseline peripheral blood eosinophil counts. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility	Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup baseline FEV1 reversibility >=12% and <12%. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted	Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER was evaluated by subgroup baseline FEV1% predicaed. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year	Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup as asthma exacerbations in the past year. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin	Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER evaluated by subgroup baseline serum periostin. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility	Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup FEV1 reversibility. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status	Severe AER was assessed based on AER data up to Week 53. An asthma exacerbation is a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 days. It was considered resolved 7 days after last dose of OCS administered (10 days after injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup Th2 status. Th2-high include participants who had IgE >100 IU/mL and blood eosinophils >=0.14*10^9/Liter. Th2 low would include participants who do not meet Th2 high status. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count	Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup baseline peripheral blood eosinophil count. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups	Prebronchodilator FEV1 was evaluated by subgroups. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups	Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups	AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status	Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. AER was evaluated by subgroup Atopic and Non-atopic asthma status. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use	Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup chronic OCS use. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Week 1 up to Week 53
Change From Baseline in Percentage of Nighttime Awakening at Week 53	Scores for nighttime awakenings were generated based on the single item (question 5) that had a dichotomous response option (YES/NO). Nighttime awakenings were averaged weekly for participants with at least 4 non-missing records each week. The baseline score was calculated with data from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
Change From Baseline in Overall Activity Limitations at Week 53	There were 3 activity limitation questions in the ASMA diary. All activity questions were scored from 0 to 4 and averaged, where the higher score indicated greater limitation. Activity limitation scores were averaged weekly for participants with at least 4 non-missing records each week. The baseline score was calculated from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53	Pre- and post-bronchodilator FEV1 at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for FEV1 was measured in liters.	Baseline and Week 53
Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53	Pre- and post-bronchodilator FEV6 at clinic visits (morning) were measured. FEV6 was the maximal volume of air exhaled in the six second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for FEV6 was measured in liters.	Baseline and Week 53
Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53	Pre- and post-bronchodilator FVC at clinic visits (morning) were measured. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for FVC was measured in liters.	Baseline and Week 53
Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53	Pre- and post-bronchodilator IC at clinic visits (morning) were measured. IC was measured by spirometry. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for IC was measured in liters.	Baseline and Week 53
Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home	Pre- and post-bronchodilator FEV1 at home (morning and evening) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home	The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at home (morning and evening) while sitting or standing prior to using any medication (if needed) for asthma. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.	Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: Edward Piper, MBBS, Sponsor GmbH; Principal Investigator: Christopher Brightling, Institute for Lung Health

Publications and helpful links

General Publications

• Baverel PG, White N, Vicini P, Karlsson MO, Agoram B. Dose-Exposure-Response Relationship of the Investigational Anti-Interleukin-13 Monoclonal Antibody Tralokinumab in Patients With Severe, Uncontrolled Asthma. Clin Pharmacol Ther. 2018 May;103(5):826-835. doi: 10.1002/cpt.803. Epub 2017 Sep 28.
• Brightling CE, Chanez P, Leigh R, O'Byrne PM, Korn S, She D, May RD, Streicher K, Ranade K, Piper E. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015 Sep;3(9):692-701. doi: 10.1016/S2213-2600(15)00197-6. Epub 2015 Jul 28.

Helpful Links

• CD-RI-CAT-354-1049 Redacted Protocol
• CD-RI-CAT-354-1049 SAP

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: July 21, 2011
• First Submitted That Met QC Criteria: July 26, 2011
• First Posted (Estimate): July 27, 2011

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 3, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Asthma; Tralokinumab; CAT-354
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CD-RI-CAT-354-1049; 2011-001360-21 (EudraCT Number)