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A Safety and Efficacy Study of Tralokinumab in Adults With Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01402986
First received: July 21, 2011
Last updated: January 10, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Asthma
Other: Placebo Q2W
Biological: Tralokinumab 300 mg, Q2W
Other: Placebo, Q2/4W
Biological: Tralokinumab 300 mg, Q2/4W
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b, Randomized, Double-blind Study to Evaluate the Efficacy of Tralokinumab in Adults With Uncontrolled, Severe Asthma

Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Annual Asthma Exacerbation Rate (AER) [ Time Frame: Week 1 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 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.


Secondary Outcome Measures:
  • Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 [ Time Frame: Baseline and 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.

  • Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 [ Time Frame: Baseline and 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.

  • Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 [ Time Frame: Baseline and 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.

  • Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 [ Time Frame: Baseline and 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.

  • Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 [ Time Frame: Baseline and 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.

  • Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home [ Time Frame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53) ]
    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.

  • Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home [ Time Frame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53) ]
    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.

  • Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53 [ Time Frame: Baseline and 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.

  • Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 [ Time Frame: Baseline and 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.

  • Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 [ Time Frame: 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.

  • Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Week 53 [ Time Frame: Baseline and 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.

  • Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53 [ Time Frame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (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.

  • Change From Baseline in Rescue Medication Use at Week 53 [ Time Frame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (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.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) [ Time Frame: Baseline and Week 75 ]
    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.

  • Observed Serum Tralokinumab Concentration at Week 53 [ Time Frame: 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.

  • Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab [ Time Frame: Baseline and Week 75 ]
    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.

  • Severe Annual Asthma Exacerbation Rate (AER) [ Time Frame: Week 1 up to Week 53 ]
    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.

  • Time to First Exacerbation Through Week 53 [ Time Frame: Week 1 up to Week 53 ]
    Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.

  • Time to First Severe Exacerbation Through Week 53 [ Time Frame: Week 1 up to Week 53 ]
    Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.

  • Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin [ Time Frame: Week 1 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. 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.

  • Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status [ Time Frame: Week 1 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. 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.

  • Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count [ Time Frame: Week 1 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. AER evaluated by subgroups baseline peripheral blood eosinophil counts. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.

  • Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility [ Time Frame: Week 1 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. AER evaluated by subgroup baseline FEV1 reversibility >=12% and <12%. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.

  • Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted [ Time Frame: Week 1 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. AER was evaluated by subgroup baseline FEV1% predicaed. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.

  • Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year [ Time Frame: Week 1 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. AER evaluated by subgroup as asthma exacerbations in the past year. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.

  • Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin [ Time Frame: Week 1 up to Week 53 ]
    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.

  • Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility [ Time Frame: Week 1 up to Week 53 ]
    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.

  • Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status [ Time Frame: Week 1 up to Week 53 ]
    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.

  • Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count [ Time Frame: Week 1 up to Week 53 ]
    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.

  • Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups [ Time Frame: Week 1 up to Week 53 ]
    Prebronchodilator FEV1 was evaluated by subgroups. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.

  • Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups [ Time Frame: Week 1 up to 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.

  • Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups [ Time Frame: Week 1 up to 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.

  • Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status [ Time Frame: Week 1 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. AER was evaluated by subgroup Atopic and Non-atopic asthma status. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.

  • Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use [ Time Frame: Week 1 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. AER evaluated by subgroup chronic OCS use. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.

  • Change From Baseline in Percentage of Nighttime Awakening at Week 53 [ Time Frame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (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.

  • Change From Baseline in Overall Activity Limitations at Week 53 [ Time Frame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (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.

  • Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 [ Time Frame: Baseline and 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.

  • Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 [ Time Frame: Baseline and 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.

  • Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 [ Time Frame: Baseline and 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.

  • Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 [ Time Frame: Baseline and 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.

  • Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home [ Time Frame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53) ]
    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.

  • Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home [ Time Frame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53) ]
    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.


Enrollment: 689
Study Start Date: August 2011
Study Completion Date: February 2014
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: CAT-354

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01402986

  Show 90 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Edward Piper, MBBS Sponsor GmbH
Principal Investigator: Christopher Brightling Institute for Lung Health
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01402986     History of Changes
Other Study ID Numbers: CD-RI-CAT-354-1049
2011-001360-21 ( EudraCT Number )
Study First Received: July 21, 2011
Results First Received: May 31, 2016
Last Updated: January 10, 2017

Keywords provided by MedImmune LLC:
Asthma
Tralokinumab
CAT-354

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 28, 2017