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

Allergen Challenge

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 Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Biological: IMA-638 is a biologic

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • University of British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3J5
      • University of British Columbia
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical
  • Quebec
    • Ste-Foy, Quebec, Canada, G1V 4G5
      • Hôpital Laval

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Gauvreau GM, Boulet LP, Cockcroft DW, Fitzgerald JM, Carlsten C, Davis BE, Deschesnes F, Duong M, Durn BL, Howie KJ, Hui L, Kasaian MT, Killian KJ, Strinich TX, Watson RM, Y N, Zhou S, Raible D, O'Byrne PM. Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma. Am J Respir Crit Care Med. 2011 Apr 15;183(8):1007-14. doi: 10.1164/rccm.201008-1210OC. Epub 2010 Nov 5.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: December 8, 2006
• First Submitted That Met QC Criteria: December 11, 2006
• First Posted (Estimate): December 12, 2006

Study Record Updates

• Last Update Posted (Estimate): November 18, 2014
• Last Update Submitted That Met QC Criteria: November 7, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 3174K1-200; B2421001 (Other Identifier: Alias Study Number)