Study to Evaluate the Safety and Efficacy of CAT-354

Study Overview
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Brief Summary
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This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel-arm study to evaluate the efficacy and safety of 3 subcutaneous (SC) treatment regimens of CAT-354 in adult subjects with uncontrolled, moderate-to-severe, persistent asthma.

Detailed Description
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Study MI-CP199, a Phase 2a, randomized, double-blind, placebo-controlled, parallel-arm, multicenter study will evaluate the effect of 3 SC treatment regimens of CAT-354 on asthma control in adults with uncontrolled, moderate-to-severe, persistent asthma.

Official Title
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A Phase 2a, Randomized, Double-blind, Placebo-Controlled, Parallel-Arm, Multicenter Study to Evaluate the Efficacy and Safety of CAT-354, a Recombinant Human Monoclonal Antibody Directed Against Interleukin-13 (IL-13), on Asthma Control in Adults With Uncontrolled, Moderate-to-severe, Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Other: Placebo
* Biological: CAT-354 150 mg
* Biological: CAT-354 300 mg
* Biological: CAT-354 600 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects Age 18 to 65 years at the time of Screening Subjects must have a body mass index (BMI) between 18 and 40 kilogram per square meter (kg/m^2) Written informed consent obtained from the subject prior to performing any protocol related procedures, including Screening evaluations Physician-diagnosed moderate-to-severe, persistent asthma requiring treatment with appropriate asthma controller medication Shows forced expiratory volume in 1 second (FEV1) reversibility postbronchodilator of greater than or equal to (>=)12 percent and >=200 milliliter (mL) or have shown such values in a previous test within the last year, or have a positive airway hyperresponsiveness (AHR) test result in the last year Pre-bronchodilator FEV 1 value >=40 percent of individual predicted value at Visits 1 and 3 Uncontrolled asthma consistent with Expert Panel Report (EPR)-3. In the 2 to 4 weeks preceding Screening, subjects should have a history of 1 or more of the following: Daytime asthma symptoms >=2 days/week, Nighttime awakening >=1 night/week, Salbutamol use >=2 days/week An Asthma control questionnaire (ACQ) score >=1.5 at Visits 1 and 3 At least 1 occurrence of asthma exacerbation in the past year that required an unscheduled medical encounter Men, unless surgically sterile, must likewise practice 2 effective methods of birth control (condom with spermicide) and must use such precautions from Day 1 through Study Day 169 Otherwise healthy by medical history and physical examination for that age group A chest x-ray or computed tomography (CT) scan within the previous 12 months with no findings suggestive of acute or chronic respiratory pathology other than asthma Ability and willingness to complete the follow-up period until Day 169 as required by the protocol. Exclusion Criteria: Known history of allergy or reaction to any component of the investigational product formulation Acute illness other than asthma at the start of the study History of an active infection within 4 weeks prior to Screening, or evidence of clinically significant active infection, including ongoing chronic infection History of ingestion of untreated water in a location known to be infected with parasites, resulting in acute or chronic diarrhea; or a diagnosis of parasitic infection within 6 months prior to Screening Use of immunosuppressive medication (except oral prednisone up to 10 milligram/day (mg/day) and inhaled and topical corticosteroids) within 30 days before randomization into the study Receipt of immunoglobulin or blood products within 30 days before randomization into the study Receipt of any investigational drug therapy or use of any biologicals including omalizumab within 6 months before the first dose of investigational product in this study or within 5 half-lives of an investigational agent or biologic, whichever is longer History of any known immunodeficiency disorder A positive hepatitis B surface antigen, or hepatitis C virus antibody A positive human immunodeficiency virus test or is taking antiretroviral medications, as determined by medical history and/or subject's verbal report A live or attenuated vaccination received within 4 weeks prior to Screening Previous medical history, or evidence, of an intercurrent illness that may compromise the safety of the subject in the study History of clinically significant abnormality on electrocardiogram (ECG) in the opinion of the investigator Lactation (women) History of treatment for alcohol or drug abuse within the past year History suggestive of chronic obstructive pulmonary disease (COPD) and of cigarette smoking >=10 pack-years Evidence of any systemic disease on physical examination History of cancer, apart from basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy less than or equal to (<=)1 year prior to Study Day 1 or other malignancies treated with apparent success with curative therapy <=5 years prior to entry Known exposure to inhaled occupational agents or fumes Any condition (eg, cystic fibrosis [CF] or COPD) that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of study results Individuals who are legally institutionalized Employees of the clinical study site or any other individuals involved with the conduct of the study, or family members of such individuals.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo matched to CAT-354 subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85. | Other: Placebo<br>* Placebo matched to CAT-354 subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.<br>|
| Experimental: CAT-354 150 mg<br>CAT-354 150 milligram (mg) subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85. | Biological: CAT-354 150 mg<br>* CAT-354 150 milligram (mg) subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.<br>* Other names: Tralokinumab;|
| Experimental: CAT-354 300 mg<br>CAT-354 300 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85. | Biological: CAT-354 300 mg<br>* CAT-354 300 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.<br>* Other names: Tralokinumab;|
| Experimental: CAT-354 600 mg<br>CAT-354 600 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85. | Biological: CAT-354 600 mg<br>* CAT-354 600 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.<br>* Other names: Tralokinumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Mean Asthma Control Questionnaire (ACQ) Score at Day 92 | 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 is 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. | Day 1 and 92 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Observed Asthma Control | Time to first asthma control was defined as the number of days from Study Day 1 to the post-baseline ACQ score measurement time point when greater than or equal to (>=) 0.5 reduction from baseline in mean ACQ score was first observed. Time to first asthma control was analyzed from Day 1 through Day 92 and up to entire study duration through Day 169. The ACQ score 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 is the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). | Day 1 to Day 92 and Day 169 | 
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Recorded at Study Sites at Day 1, 15, 29, 43, 57, 71, 85, 92, 127 and 169 | Forced Expiratory Volume in 1 Second (FEV1) is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Spirometry was performed with the participant in the sitting/standing (kept consistent at each visit) position at study sites by the investigator or qualified designee according to American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. Multiple forced expiratory efforts (at least 3 but no more than 8) were performed for each office spirometry session and the 2 best efforts that met ATS/ERS acceptability and reproducibility criteria were recorded. The best efforts were based on the highest FEV1. The maximum FEV1 of the 2 best efforts was used for the analysis. Data collected on Day 1 prior to dosing was considered as baseline. | Day 1, 15, 29, 43, 57, 71, 85, 92, 127 and 169 | 
| Change From Baseline in Peak Expiratory Flow (PEF) Recorded at Home Every Week From Day 1 to 169 | The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Home peak flow testing for PEF was performed every morning while sitting or standing prior to using any medication (if needed) for asthma. Mean of the data was collected over 1 week prior to dosing on Day 1 was considered as baseline. Mean PEF values for each week were used to calculate the change from baseline values starting from Day 2 to 169. | Day -7 to 1 (predose), Day 2 to 169 | 
| Number of Puffs of Rescue Beta-2 Agonist Per Week | Number of Puffs of Rescue Beta-2 Agonist Per Week Rescue beta-2 agonist use (total number of puffs for the preceding week) was collected daily in the morning by the participants in the daily diary provided to them. Average values for each week were reported starting from Day -7 to Day 169. | Day -7 to 169 | 
| Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores | Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]): a 32-item questionnaire that measures the functional impairments experienced by adult participants 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). | Day 1, 29, 57, 92, 127 and 169 | 
| Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores at Day 29, 57, 92, 127 and 169 | Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]): a 32-item questionnaire that measures the functional impairments experienced by adult participants 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 collected on Day 1 prior to dosing was considered as baseline | Day 1, 29, 57, 92, 127 and 169 | 
| Patient Global Impression of Change (PGIC) | Patient Global Impression of Change (PGIC): participant rated instrument to measure participant's change in overall status compared to baseline on a 7-point scale; range from 1 (very much worse) to 7 (very much better). | Day 92 and 169 | 
| Percentage of Participants With Mean Asthma Control Questionnaire (ACQ) Score Less Than or Equal to 0.75 or ACQ Score Greater Than 0.75 But Less Than 1.5 | Percentage of participants with mean Asthma Control Questionnaire (ACQ) score less than or equal to (<=) 0.75 or mean ACQ score greater than (>) 0.75 and less than (<) 1.5 were analyzed. The 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 is the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Mean ACQ scores of less than or equal to (<=) 0.75 indicated well-controlled asthma, mean ACQ scores greater than (>) 0.75 but less than (<) 1.5 indicated partly controlled asthma. | Day 92 and 169 | 
| Serum Concentration for CAT-354 |  | Predose on Day 15, 29, 43, 57, 71 and 85; Day 88, 92, 99, 127, and 169 | 
| Number of Participants With Anti-Drug Antibodies to CAT-354 at Any Visit |  | Day 1, 92 and 169 | 
| Percentage of Participants With Positive Serum Antibodies to CAT-354 at Any Visit |  | Day 1, 92 and 169 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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 first dose of study drug and Day 169 that were absent before treatment or that worsened relative to pretreatment state. | Day 1 to 169 | 
| Percentage of Participants With at Least 1 Moderate or Severe Exacerbation | Asthma exacerbation was defined as either a progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) or a reduction of >= 20 percent (%) in PEF or FEV1 from baseline that did not resolve after the initiation of rescue medications and resulted in an administration of systemic corticosteroids by the investigator or health care provider. Asthma exacerbation severity was classified as: 1) Moderate-worsening symptoms that required systemic corticosteroids. 2) Severe-worsening symptoms that required systemic corticosteroids and hospital admission. | Day 92 and 169 | 
| Moderate or Severe Asthma Exacerbations Per Person Per Annum | Asthma exacerbation was defined as either a progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) or a reduction of >=20% in PEF or FEV1 from baseline that did not resolve after the initiation of rescue medications and resulted in an administration of systemic corticosteroids by the investigator or health care provider. Asthma exacerbation rate, calculated as total asthma exacerbations per person per annum, was assessed based on asthma exacerbation data up to Day 92 and 169 (Rate = mean asthma exacerbations for all participants/X days*365 days, where X = 92 or 169). | Day 1 to Day 92 and Day 169 | 
| Time to First Moderate or Severe Asthma Exacerbation | Time to first moderate or severe asthma exacerbation was defined as time to first observed progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) or a reduction of >=20% in PEF or FEV1 from baseline that did not resolve after the initiation of rescue medications and resulted in an administration of systemic corticosteroids by the investigator or health care provider. | Day 1 to Day 92 and Day 169 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAT-354, Tralokinumab, Asthma