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

Pfizer30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Asthma

Interventions

IMA-638 is a biologicBIOLOGICAL

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

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:

Locations (4)

University of British Columbia

Vancouver, British Columbia, Canada

University of British Columbia

Vancouver, British Columbia, Canada

McMaster University Medical

Hamilton, Ontario, Canada

Hopital Laval

Ste-Foy, Quebec, Canada

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

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

Blood Levels of Interleukin-13 (IL-13)

Time frame: 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.

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

Protein Expression in Sputum and Blood

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

Maximum Observed Serum Concentration (Cmax) for IMA-638