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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00410280
First received: December 8, 2006
Last updated: November 7, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Asthma
Biological: IMA-638 is a biologic
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Allergen Challenge

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Maximum Percent Drop From Pre-allergen Baseline in Forced Expiratory Volume in 1 Second (FEV1) for Late-Phase Asthma Response (LAR) at Screening [ Time Frame: Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Screening (Day -14) ] [ Designated as safety issue: No ]
    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.

  • Maximum Percent Drop From Pre-allergen Baseline in Forced Expiratory Volume in 1 Second (FEV1) for Late-Phase Asthma Response (LAR) at Day 14 [ Time Frame: Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Day 14 ] [ Designated as safety issue: No ]
    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.

  • Maximum Percent Drop From Pre-allergen Baseline in Forced Expiratory Volume in 1 Second (FEV1) for Late-Phase Asthma Response (LAR) at Day 35 [ Time Frame: Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Day 35 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) [ Time Frame: Pre-allergen baseline, 3, 4, 5, 6, 7 hours post-allergen inhalation at Screening (Day -14), Day 14, 35 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Pre-allergen baseline, 10, 20, 30, 45, 60, 90, 120, 180 minutes post-allergen inhalation Screening, Day 14, 35 ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: Pre-allergen baseline, 10, 20, 30, 45, 60, 90, 120, 180 minutes post-allergen inhalation Screening, Day 14, 35 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day -15, -13 for Screening (Day -14) challenge; Day 13, 15 for Day 14 challenge; Day 34, 36 for Day 35 challenge ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Total and Differential Sputum Cell Counts at Day 14 and 35 [ Time Frame: Baseline, Day 14, 35 ] [ Designated as safety issue: No ]
    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.

  • Allergen Specific and Total Immunoglobulin E (IgE) Count at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Allergen Specific and Total Immunoglobulin E (IgE) Count at Day 13, 34, 56, 112 and 168 [ Time Frame: Baseline, Day 13, 34, 56, 112, 168 ] [ Designated as safety issue: No ]
    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.

  • Total Blood Eosinophil Counts at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Total Blood Eosinophil Counts at Day 8, 13, 21, 34, 56, 84 and 168 [ Time Frame: Baseline, Day 8, 13, 21, 34, 56, 84, 168 ] [ Designated as safety issue: No ]
    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).

  • Blood Levels of Interleukin-13 (IL-13) [ Time Frame: Screening, baseline, Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 ] [ Designated as safety issue: No ]
  • Messenger Ribonucleic Acid (mRNA) Gene Expression in Sputum and Blood [ Time Frame: Screening (Day-13, -14, -15), Day 1, 13, 14, 15, 34, 35, 36, 112 ] [ Designated as safety issue: No ]
    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.

  • Protein Expression in Sputum and Blood [ Time Frame: Screening (Day-13, -14, -15), Day 1, 13, 14, 15, 34, 35, 36, 112 ] [ Designated as safety issue: No ]
    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.

  • Maximum Observed Serum Concentration (Cmax) for IMA-638 [ Time Frame: Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax) for IMA-638 [ Time Frame: Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] for IMA-638 [ Time Frame: Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUC0-t).

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for IMA-638 [ Time Frame: Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 ] [ Designated as safety issue: No ]
    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 - ∞).

  • Serum Decay Half-Life (t1/2) for IMA-638 [ Time Frame: Day 1, 8, 14, 21, 35, 56, 84, 112, 140, 168 ] [ Designated as safety issue: No ]
    Serum decay half-life is the time measured for the serum concentration to decrease by one half.

  • Number of Participants With Antibodies to IMA-638 [ Time Frame: Baseline up to Day 168 ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: March 2007
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 Biological: IMA-638 is a biologic

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00410280

Locations
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, V5Z 3J5
University of British Columbia
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
McMaster University Medical
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Quebec
Hopital Laval
Ste-Foy, Quebec, Canada, G1V 4G5
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00410280     History of Changes
Other Study ID Numbers: 3174K1-200, B2421001
Study First Received: December 8, 2006
Results First Received: November 7, 2014
Last Updated: November 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on November 25, 2014