Study Evaluating the Effect of IMA-638 in Subjects With Persistent Asthma

Study Overview
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Brief Summary
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Primary purpose is to assess if IMA-638 is safe and improves asthma in subjects with persistent asthma.

Official Title
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Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2 Study Conducted Sequentially With 3 Doses Of Ima-638 Administered Sc.

Conditions
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Asthma

Intervention / Treatment
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* Biological: IMA-638
* Biological: IMA-638
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy men and women with persistent asthma, 18 to 70 years of age, with body weight between 50 kg and 115 kg. History of treatment with a medium to high dose of inhaled corticosteroids (ICS), with or without long-acting beta-agonists (LABA), for at least 2 months prior to the screening visit and must remain constant during the study. FEV1 ≥ 55% to ≤ 80% predicted and demonstrated improvement in FEV1 (L) with inhaled albuterol (salbutamol) (reversibility) of ≥ 12%. Exclusion Criteria:

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: IMA-638<br>* SC Injection, 12 weeks<br>|
| Experimental: 2<br> | Biological: IMA-638<br>* SC Injection, 12 weeks<br>|
| Placebo Comparator: 3<br> | Other: placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 | The PEFR is a participant's maximum speed of expiration, as measured with a peak flow meter. All participants were issued with the peak flow meter and instructed to perform the activity in triplicate in the morning prior to taking bronchodilator. The best among the 3 readings was selected. | Baseline, Day 112 | 
| Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 2/3 | The PEFR is a participant's maximum speed of expiration, as measured with a peak flow meter. All participants were issued with the peak flow meter and instructed to perform the activity in triplicate in the morning prior to taking bronchodilator. The best among the 3 readings was selected. | Baseline, Day 112 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Participants performed the test in triplicate at each visit and the best of the 3 values was selected. | Baseline, Day 8, 28, 56, 84, 112 | 
| Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Participants performed the test in triplicate at each visit and the best of the 3 values was selected. | Baseline, Day 8, 28, 56, 84, 112 | 
| Change From Baseline in Airway Hyper-reactivity at Day 28 and 112 | Airway hyper-reactivity was assessed using provocative concentration 20 (PC20). PC20 was the concentration of methacholine at which participants had 20 percent (%) decrease in FEV1. Results for PC20 were summarized together for all participants who received any dose of IMA-638 and for all participants who received placebo during any stage of the study as per investigator's discretion. | Baseline, Day 28, 112 | 
| Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | ACQ-5 was a 5-item participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing). Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score was the mean of the responses. Mean scores of less than or equal to (=<) 0.75 indicate well-controlled asthma, scores between 0.76 and less than (<) 1.5 indicate partly controlled asthma, and a score greater than or equal to (>=) 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful. | Baseline, Day 8, 28, 56, 84, 112 | 
| Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | ACQ-5 was a 5-item participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing). Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score was the mean of the responses. Mean scores of =< 0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful. | Baseline, Day 8, 28, 56, 84, 112 | 
| Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 1 |  | Baseline up to Day 112 | 
| Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 2/3 |  | Baseline up to Day 112 | 
| Mean Number of Puffs of Rescue Medication Used - Stage 1 | The rescue medication taken for needed symptoms was a short acting beta agonist (SABA) inhaler. Albuterol, 90 microgram (mcg)/puff, was recommended for use. | Day 8, 28, 56, 84, 89, 91, 94, 98, 112 | 
| Mean Number of Puffs of Rescue Medication Used - Stage 2/3 | The rescue medication taken for needed symptoms was a SABA inhaler. Albuterol, 90 mcg/puff, was recommended for use. | Day 8, 28, 56, 84, 89, 91, 94, 98, 112 | 
| Forced Vital Capacity (FVC) - Stage 1 | FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. | Baseline, Day 8, 28, 56, 84, 112 | 
| Forced Vital Capacity (FVC) - Stage 2/3 | FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. | Baseline, Day 8, 28, 56, 84, 112 | 
| Forced Mid-Expiratory Flow Rate 25 Percent (%) to 75% (FEF25-75) - Stage 1 | FEF25-75 is the average expiratory flow over the middle half of the FVC. FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. | Baseline, Day 8, 28, 56, 84, 112 | 
| Forced Mid-Expiratory Flow Rate 25 Percent (%) to 75% (FEF25-75) - Stage 2/3 | FEF25-75 is the average expiratory flow over the middle half of the FVC. FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. | Baseline, Day 8, 28, 56, 84, 112 | 
| Blood Eosinophils Levels - Stage 1 |  | Baseline, Day 8, 28, 56, 84, 112 | 
| Blood Eosinophils Levels - Stage 2/3 |  | Baseline, Day 8, 28, 56, 84, 112 | 
| Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Log 10-transformed serum total IgE levels were expressed in Log-10 International units/milliliter (IU/mL). | Baseline, Day 28, 56, 84, 112 | 
| Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Log 10-transformed serum total IgE levels were expressed in Log-10 International units/milliliter (IU/mL). | Baseline, Day 28, 56, 84, 112 | 
| Serum Interleukin-13 (IL-13) Level - Stage 1 |  | Baseline, Day 8, 28, 56, 84, 112 | 
| Serum Interleukin-13 (IL-13) Level - Stage 2/3 |  | Baseline, Day 8, 28, 56, 84, 112 |