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

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.

Time frame: Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Day 14

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article.

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.

Time frame: Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Day 35

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article.

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.

Time frame: Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Screening (Day -14)

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article.

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.

Time frame: Baseline

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article. Allergen-specific IgE was not analyzed because the study was stopped early after interim analysis and only safety and key efficacy analyses were performed.

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 - ∞).

Time frame: Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168

Population: Evaluable population included all randomized participants who received at least 1 dose administration of the test article and had evaluable pharmacokinetic data.

Area under the plasma concentration time-curve from zero to the last measured concentration (AUC0-t).

Time frame: Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168

Population: Evaluable population included all randomized participants who received at least 1 dose administration of the test article and had evaluable pharmacokinetic data.

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.

Time frame: Pre-allergen baseline, 10, 20, 30, 45, 60, 90, 120, 180 minutes post-allergen inhalation Screening, Day 14, 35

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article.

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.

Time frame: Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Screening (Day -14), Day 14, 35

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article.

Time frame: Screening, baseline, Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168

Population: Data for this outcome measure was not analyzed because the study was stopped early after interim analysis and only safety and key efficacy analyses were performed.

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.

Time frame: Baseline, Day 13, 34, 56, 112, 168

Population: ITT population. Here, n signifies participants evaluated for this measure at the specified time point for each arm. Allergen-specific IgE was not analyzed because the study was stopped early after interim analysis and only safety and key efficacy analyses were performed.

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.

Time frame: Baseline, Day 14, 35

Population: Data was not analyzed because the study was stopped early after interim analysis and only safety and key efficacy analyses were performed.

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).

Time frame: Baseline, Day 8, 13, 21, 34, 56, 84, 168

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article. Here, n signifies participants evaluated for this measure at the specified time point for each arm.

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).

Time frame: Day -15, -13 for Screening (Day -14) challenge; Day 13, 15 for Day 14 challenge; Day 34, 36 for Day 35 challenge

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article.

Time frame: Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168

Population: Evaluable population included all randomized participants who received at least 1 dose administration of the test article and had evaluable pharmacokinetic data.

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.

Time frame: Pre-allergen baseline, 10, 20, 30, 45, 60, 90, 120, 180 minutes post-allergen inhalation Screening, Day 14, 35

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article.

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.

Time frame: Screening (Day-13, -14, -15), Day 1, 13, 14, 15, 34, 35, 36, 112

Population: Data for this outcome measure was not analyzed because the study was stopped early after interim analysis and only safety and key efficacy analyses were performed.

Time frame: Baseline up to Day 168

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article.

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.

Time frame: Screening (Day-13, -14, -15), Day 1, 13, 14, 15, 34, 35, 36, 112

Population: Data for this outcome measure w as not analyzed because the study w as stopped early after interim analysis and only safety and key efficacy analyses w ere performed.

Serum decay half-life is the time measured for the serum concentration to decrease by one half.

Time frame: Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168

Population: Evaluable population included all randomized participants who received at least 1 dose administration of the test article and had evaluable pharmacokinetic data.

Time frame: Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168

Population: Evaluable population included all randomized participants who received at least 1 dose administration of the test article and had evaluable pharmacokinetic data.

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).

Time frame: Baseline

Population: ITT population included all randomized participants who received at least 1 dose administration of the test article.