Study Evaluating the Effects of IMA-638 on Allergen-Induced Airway Responses in Subjects With Mild Atopic Asthma

Study Overview
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Brief Summary
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Primary purpose of the protocol is to determine if IMA-638 prevents a mild asthma attack by a subject with mild asthma inhaling an allergen.

Official Title
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Allergen Challenge

Conditions
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Asthma

Intervention / Treatment
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* Biological: IMA-638 is a biologic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria: generally healthy, men and women with mild allergic asthma, aged 18 to 60 years only asthma med is short-acting bronchodilator used not more than twice weekly FEV1 greater than 70% predicted and a demonstrated baseline late response to allergen induction Exclusion Criteria:

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br> | Biological: IMA-638 is a biologic<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Percent Drop From Pre-allergen Baseline in Forced Expiratory Volume in 1 Second (FEV1) for Late-Phase Asthma Response (LAR) at Screening | Allergen inhalation test was performed at Screening, Day 14 and 35 to elicit airway responses similar to those that follow natural allergen exposure. FEV1 was the maximal volume of air exhaled in 1 second of a forced expiration from a position of full inspiration. LAR was characterized by a fall in FEV1 of more than or equal to (>=) 15 percent (%) at 3 to 7 hours post-allergen inhalation. Maximum drop in FEV1 relative to the pre-allergen baseline FEV1 between 3 to 7 hours at Screening was reported. Pre-allergen baseline FEV1 was performed in triplicate using spirometry and the best of the 3 values was selected. | Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Screening (Day -14) | 
| Maximum Percent Drop From Pre-allergen Baseline in Forced Expiratory Volume in 1 Second (FEV1) for Late-Phase Asthma Response (LAR) at Day 14 | Allergen inhalation test was performed at Screening, Day 14 and 35 to elicit airway responses similar to those that follow natural allergen exposure. FEV1 was the maximal volume of air exhaled in 1 second of a forced expiration from a position of full inspiration. LAR was characterized by a fall in FEV1 of more than or equal to (>=) 15 percent (%) at 3 to 7 hours post-allergen inhalation. Maximum drop in FEV1 relative to the pre-allergen baseline FEV1 between 3 to 7 hours on Day 14 was reported. Pre-allergen baseline FEV1 was performed in triplicate using spirometry and the best of the 3 values was selected. | Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Day 14 | 
| Maximum Percent Drop From Pre-allergen Baseline in Forced Expiratory Volume in 1 Second (FEV1) for Late-Phase Asthma Response (LAR) at Day 35 | Allergen inhalation test was performed at Screening, Day 14 and 35 to elicit airway responses similar to those that follow natural allergen exposure. FEV1 was the maximal volume of air exhaled in 1 second of a forced expiration from a position of full inspiration. LAR was characterized by a fall in FEV1 of more than or equal to (>=) 15 percent (%) at 3 to 7 hours post-allergen inhalation. Maximum drop in FEV1 relative to the pre-allergen baseline FEV1 between 3 to 7 hours on Day 35 was reported. Pre-allergen baseline FEV1 was performed in triplicate using spirometry and the best of the 3 values was selected. | Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Percent Drop in Forced Expiratory Volume in 1 Second Curve (AUC FEV1) From Time 3 to 7 Hours for Late-Phase Asthma Response (LAR) | Allergen inhalation test was performed at Screening, Day 14 and 35 to elicit airway responses similar to those that follow natural allergen exposure. FEV1 was the maximal volume of air exhaled in 1 second of a forced expiration from a position of full inspiration. LAR was characterized by a fall in FEV1 of >=15% at 3 to 7 hours post-allergen inhalation. Area under the percent drop in FEV1 relative to the pre-allergen baseline FEV1 from 3 to 7 hours was computed using the linear trapezoidal rule. Pre-allergen baseline FEV1 was performed in triplicate using spirometry and the best of the 3 values was selected. | Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Screening (Day -14), Day 14, 35 | 
| Maximum Percent Drop From Pre-allergen Baseline in Forced Expiratory Volume in 1 Second (FEV1) for Early-Phase Asthma Response (EAR) at Screening, Day 14 and 35 | Allergen inhalation test was performed at Screening, Day 14 and 35 to elicit airway responses similar to those that follow natural allergen exposure. FEV1 was the maximal volume of air exhaled in 1 second of a forced expiration from a position of full inspiration. EAR was characterized by a fall in FEV1 >=20% at 0 to 3 hours post-allergen inhalation. Maximum drop in FEV1 relative to the pre-allergen baseline FEV1 between 0 to 3 hours was reported. Pre-allergen baseline FEV1 was performed in triplicate using spirometry and the best of the 3 values was selected. | Pre-allergen baseline, 10, 20, 30, 45, 60, 90, 120, 180 minutes post-allergen inhalation Screening, Day 14, 35 | 
| Area Under the Percent Drop in Forced Expiratory Volume in 1 Second Curve (AUC FEV1) From Time 0 to 3 Hours for Early-Phase Asthma Response (EAR) | Allergen inhalation test was performed at Screening, Day 14 and 35 to elicit airway responses similar to those that follow natural allergen exposure. FEV1 was the maximal volume of air exhaled in 1 second of a forced expiration from a position of full inspiration. EAR was characterized by a fall in FEV1 >=20% at 0 to 3 hours post-allergen inhalation. Area under the percent drop in FEV1 relative to the pre-allergen baseline FEV1 from 0 to 3 hours at each visit was computed using the linear trapezoidal rule. Pre-allergen baseline FEV1 was performed in triplicate using spirometry and the best of the 3 values was selected. | Pre-allergen baseline, 10, 20, 30, 45, 60, 90, 120, 180 minutes post-allergen inhalation Screening, Day 14, 35 | 
| Change From Pre-allergen Challenge in Provocative Concentration of Methacholine Causing a 20% Fall in FEV1 (PC20) to Post-allergen Challenge For Screening, Day 14 and 35 Challenge | Methacholine inhalation test was performed to determine airway hyper-reactivity using provocative concentration 20 (PC20). PC20 was the lowest concentration of methacholine at which participant had 20% decrease from baseline in FEV1. Pre-allergen challenge methacholine inhalation test was performed 1 day prior to the allergen challenge and post-allergen challenge methacholine inhalation test was performed 1 day after to the allergen challenge (that is, pre- and post-allergen methacholine inhalation test was conducted on Day -15 and -13 for Screening allergen challenge, Day 13 and 15 for Day 14 allergen challenge and Day 34 and 36 for Day 35 allergen challenge, respectively). For each methacholine inhalation test, baseline FEV1 was defined as the lowest value among the triplicate readings taken after administration of the diluent (saline administration). Difference between post-allergen challenge and pre-allergen challenge was expressed as log2 (post-allergen PC20 - pre-allergen PC20). | Day -15, -13 for Screening (Day -14) challenge; Day 13, 15 for Day 14 challenge; Day 34, 36 for Day 35 challenge | 
| Change From Baseline in Total and Differential Sputum Cell Counts at Day 14 and 35 | The collected sputum was planned to be analyzed for epithelial cells, eosinophils, lymphocytes, neutrophils, metachromatic cells, or macrophages counts. Sputum induction was to be performed after each methacholine challenge and at 7 hours after each allergen inhalation challenge. | Baseline, Day 14, 35 | 
| Allergen Specific and Total Immunoglobulin E (IgE) Count at Baseline | The baseline for the outcome measure was defined as the last post-dose measurement obtained prior to the allergen challenge within a given challenge triad (planned on day 13 and 34). The challenge triad included pre-allergen methacholine inhalation challenge, allergen inhalation challenge, and post-allergen methacholine inhalation challenge. Results are reported for total IgE count. | Baseline | 
| Change From Baseline in Allergen Specific and Total Immunoglobulin E (IgE) Count at Day 13, 34, 56, 112 and 168 | The baseline for the outcome measure was defined as the last post-dose measurement obtained prior to the allergen challenge (planned on Day 13 and 34). Results are reported for total IgE count. | Baseline, Day 13, 34, 56, 112, 168 | 
| Total Blood Eosinophil Counts at Baseline | The baseline for the outcome measure was defined as the last post-dose measurement obtained prior to the allergen challenge (planned on day 13 and 34). | Baseline | 
| Change From Baseline in Total Blood Eosinophil Counts at Day 8, 13, 21, 34, 56, 84 and 168 | The baseline for the outcome measure was defined as the last post-dose measurement obtained prior to the allergen challenge (planned on Day 13 and 34). | Baseline, Day 8, 13, 21, 34, 56, 84, 168 | 
| Blood Levels of Interleukin-13 (IL-13) |  | Screening, baseline, Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 | 
| Messenger Ribonucleic Acid (mRNA) Gene Expression in Sputum and Blood | Sputum induction was performed after each methacholine challenge and at hour 7 after each allergen inhalation challenge. The baseline for this outcome measure was defined as the last value prior to dosing. | Screening (Day-13, -14, -15), Day 1, 13, 14, 15, 34, 35, 36, 112 | 
| Protein Expression in Sputum and Blood | Sputum induction was performed after each methacholine challenge and at hour 7 after each allergen inhalation challenge. The baseline for this outcome measure was defined as the last value prior to dosing. | Screening (Day-13, -14, -15), Day 1, 13, 14, 15, 34, 35, 36, 112 | 
| Maximum Observed Serum Concentration (Cmax) for IMA-638 |  | Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 | 
| Time to Reach Maximum Observed Serum Concentration (Tmax) for IMA-638 |  | Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] for IMA-638 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUC0-t). | Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for IMA-638 | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 | 
| Serum Decay Half-Life (t1/2) for IMA-638 | Serum decay half-life is the time measured for the serum concentration to decrease by one half. | Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 | 
| Number of Participants With Antibodies to IMA-638 |  | Baseline up to Day 168 |