Study Evaluating the Effect of IMA-638 in Subjects With Persistent Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00425061
First received: January 18, 2007
Last updated: January 12, 2015
Last verified: January 2015
  Purpose

Primary purpose is to assess if IMA-638 is safe and improves asthma in subjects with persistent asthma.


Condition Intervention Phase
Asthma
Biological: IMA-638
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2 Study Conducted Sequentially With 3 Doses Of Ima-638 Administered Sc.

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 [ Time Frame: Baseline, Day 112 ] [ Designated as safety issue: No ]
    The PEFR is a participant's maximum speed of expiration, as measured with a peak flow meter. All participants were issued with the peak flow meter and instructed to perform the activity in triplicate in the morning prior to taking bronchodilator. The best among the 3 readings was selected.

  • Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 2/3 [ Time Frame: Baseline, Day 112 ] [ Designated as safety issue: No ]
    The PEFR is a participant's maximum speed of expiration, as measured with a peak flow meter. All participants were issued with the peak flow meter and instructed to perform the activity in triplicate in the morning prior to taking bronchodilator. The best among the 3 readings was selected.


Secondary Outcome Measures:
  • Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
    FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Participants performed the test in triplicate at each visit and the best of the 3 values was selected.

  • Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
    FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Participants performed the test in triplicate at each visit and the best of the 3 values was selected.

  • Change From Baseline in Airway Hyper-reactivity at Day 28 and 112 [ Time Frame: Baseline, Day 28, 112 ] [ Designated as safety issue: No ]
    Airway hyper-reactivity was assessed using provocative concentration 20 (PC20). PC20 was the concentration of methacholine at which participants had 20 percent (%) decrease in FEV1. Results for PC20 were summarized together for all participants who received any dose of IMA-638 and for all participants who received placebo during any stage of the study as per investigator's discretion.

  • Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
    ACQ-5 was a 5-item participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing). Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score was the mean of the responses. Mean scores of less than or equal to (=<) 0.75 indicate well-controlled asthma, scores between 0.76 and less than (<) 1.5 indicate partly controlled asthma, and a score greater than or equal to (>=) 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.

  • Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
    ACQ-5 was a 5-item participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing). Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score was the mean of the responses. Mean scores of =< 0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.

  • Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 1 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 2/3 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: No ]
  • Mean Number of Puffs of Rescue Medication Used - Stage 1 [ Time Frame: Day 8, 28, 56, 84, 89, 91, 94, 98, 112 ] [ Designated as safety issue: No ]
    The rescue medication taken for needed symptoms was a short acting beta agonist (SABA) inhaler. Albuterol, 90 microgram (mcg)/puff, was recommended for use.

  • Mean Number of Puffs of Rescue Medication Used - Stage 2/3 [ Time Frame: Day 8, 28, 56, 84, 89, 91, 94, 98, 112 ] [ Designated as safety issue: No ]
    The rescue medication taken for needed symptoms was a SABA inhaler. Albuterol, 90 mcg/puff, was recommended for use.

  • Forced Vital Capacity (FVC) - Stage 1 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
    FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  • Forced Vital Capacity (FVC) - Stage 2/3 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
    FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  • Forced Mid-Expiratory Flow Rate 25 Percent (%) to 75% (FEF25-75) - Stage 1 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
    FEF25-75 is the average expiratory flow over the middle half of the FVC. FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  • Forced Mid-Expiratory Flow Rate 25 Percent (%) to 75% (FEF25-75) - Stage 2/3 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
    FEF25-75 is the average expiratory flow over the middle half of the FVC. FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  • Blood Eosinophils Levels - Stage 1 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
  • Blood Eosinophils Levels - Stage 2/3 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
  • Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 [ Time Frame: Baseline, Day 28, 56, 84, 112 ] [ Designated as safety issue: No ]
    Log 10-transformed serum total IgE levels were expressed in Log-10 International units/milliliter (IU/mL).

  • Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 [ Time Frame: Baseline, Day 28, 56, 84, 112 ] [ Designated as safety issue: No ]
    Log 10-transformed serum total IgE levels were expressed in Log-10 International units/milliliter (IU/mL).

  • Serum Interleukin-13 (IL-13) Level - Stage 1 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]
  • Serum Interleukin-13 (IL-13) Level - Stage 2/3 [ Time Frame: Baseline, Day 8, 28, 56, 84, 112 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance Stage 1 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: Yes ]
    Criteria for potentially clinically important (PCI) vital sign abnormalities- heart rate: greater than (>) 15 beats per minute (bpm) increase from baseline and greater than or equal to (>=) 120 bpm, >15 bpm decrease from baseline and less than or equal to (<=) 45 bpm: systolic blood pressure (SBP): >=20 millimeter of mercury (mmHg) increase from baseline and >=160 mmHg, >=20 mmHg decrease from baseline and <=90 mmHg: diastolic blood pressure (DBP): of >=15 mmHg increase from baseline and >=100 mmHg, >=15 mmHg decrease from baseline and <=50 mmHg, oral temperature <35 or >38.3 degrees centigrade: respiratory rate: <10 or >25 breaths/minute: body weight: >=7% increase or decrease from baseline.

  • Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance - Stage 2/3 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: Yes ]
    Criteria for PCI vital sign abnormalities- heart rate: >15 bpm increase from baseline and >=120 bpm, >15 bpm decrease from baseline and <=45 bpm: SBP: >=20 mmHg increase from baseline and >=160 mmHg, >=20 mmHg decrease from baseline and <=90 mmHg: DBP: of >=15 mmHg increase from baseline and >=100 mmHg, >=15 mmHg decrease from baseline and <=50 mmHg, oral temperature <35 or >38.3 degrees centigrade: respiratory rate: <10 or >25 breaths/minute: body weight: >=7% increase or decrease from baseline.

  • Number of Participants With Clinically Important Changes in Physical Findings - Stage 1 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: Yes ]
    Physical examination included examination of general appearance, skin, head, ears, eyes, nose, throat, heart, lungs, breasts, abdomen, external genitalia, extremities, neurological exam, back/spine and lymph nodes.

  • Number of Participants With Clinically Important Changes in Physical Findings - Stage 2/3 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: Yes ]
    Physical examination included examination of general appearance, skin, head, ears, eyes, nose, throat, heart, lungs, breasts, abdomen, external genitalia, extremities, neurological exam, back/spine and lymph nodes.

  • Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 1 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: Yes ]
    Clinically significant ECG findings included - heart rate: >15 bpm increase from baseline and >=120 bpm, PR interval: >=20 millisecond (msec) change from baseline and >=220 msec: QRS interval: >=120 msec: corrected QT (QTc) interval: >450 msec for males and >470 msec for females.

  • Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 2/3 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: Yes ]
    Clinically significant ECG findings included - heart rate: >15 bpm increase from baseline and >=120 bpm, PR interval: >=20 msec change from baseline and >=220 msec: QRS interval: >=120 msec: QTc interval: >450 msec for males and >470 msec for females.

  • Number of Participants With Injection Site Reaction - Stage 1 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Injection Site Reaction - Stage 2/3 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 1 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: Yes ]
    Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils); hepatobiliary biochemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, gamma glutamyl transferase (GGT), total lactate dehydrogenase (LDH); renal function tests: blood urea nitrogen (BUN), creatinine, creatinine kinase, uric acid, albumin; electrolytes: sodium, potassium, calcium, magnesium, phosphorus; coagulation: prothrombin time and partial thromboplastin time; glucose: fasting, non-fasting; lipid profile: total cholesterol, triglycerides.

  • Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 2/3 [ Time Frame: Baseline up to Day 112 ] [ Designated as safety issue: Yes ]
    Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils); hepatobiliary biochemistry: ALT, AST, alkaline phosphatase, total bilirubin, GGT, total LDH; renal function tests: BUN, creatinine, creatinine kinase, uric acid, albumin; electrolytes: sodium, potassium, calcium, magnesium, phosphorus; coagulation: prothrombin time and partial thromboplastin time; glucose: fasting, non-fasting; lipid profile: total cholesterol, triglycerides.


Enrollment: 159
Study Start Date: February 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Biological: IMA-638
SC Injection, 12 weeks
Experimental: 2 Biological: IMA-638
SC Injection, 12 weeks
Placebo Comparator: 3 Other: placebo
placebo

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Generally healthy men and women with persistent asthma, 18 to 70 years of age, with body weight between 50 kg and 115 kg.
  • History of treatment with a medium to high dose of inhaled corticosteroids (ICS), with or without long-acting beta-agonists (LABA), for at least 2 months prior to the screening visit and must remain constant during the study.
  • FEV1 ≥ 55% to ≤ 80% predicted and demonstrated improvement in FEV1 (L) with inhaled albuterol (salbutamol) (reversibility) of ≥ 12%.

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: NCT00425061

  Show 82 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00425061     History of Changes
Other Study ID Numbers: 3174K1-201, B2421007
Study First Received: January 18, 2007
Results First Received: November 6, 2014
Last Updated: January 12, 2015
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on August 02, 2015