Clinical Trial: A Study to Evaluate the Efficacy and Safety of Reslizumab in Patients With Eosinophilic Asthma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A 12-Month, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in Patients (12-75 Ye

Brief Summary: The primary objective of this study is to determine whether reslizumab is more effective than placebo in reducing the number of clinical asthma exacerbations (CAEs) in patients with eosinophilic asthma.

Detailed Summary:
Sponsor: Teva Branded Pharmaceutical Products, R&D Inc.

Current Primary Outcome:

  • Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment [ Time Frame: Day 1 to Month 12 ]

    An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma:

    • use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids.
    • asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization.

    CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors.

    Results are offered as adjusted means.

  • Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) [ Time Frame: Day 1 to Month 12 ]

    An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma:

    • Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) At Week 16 [ Time Frame: Day 1 (baseline, pre-dose), Week 16 ]

      FEV1 is a standard measurement of air movement in the lungs of patients with asthma obtained from pulmonary function tests. It is the volume of air expired in the first second of a forced expiration using a spirometer.

      Positive change from baseline scores indicate improvement in asthma control.

    • Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12 and 16 ]

      FEV1 is a standard measurement of air movement in the lungs of patients with asthma obtained from pulmonary function tests. It is the volume of air expired in the first second of a forced expiration using a spirometer. During study (Weeks 4, 8, 12 and 16) average value used a mixed effect model for repeated measures (MMRM) with treatment group, visit, treatment and visit interaction, and stratification factors as fixed effects and participant as a random effect. Covariates for baseline values were also included in the model; for pulmonary function test analyses, covariates for height and sex were included as well.

      Positive change from baseline scores indicate improvement in asthma control.

    • Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16 [ Time Frame: Day 1 (baseline, pre-dose), Week 16 ]

      The AQLQ is a 32-item instrument administered as a self-assessment (Juniper et al 1992). The questionnaire is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (1=severe impairment, 7=no impairment). The overall AQLQ score is the mean of all 32 responses. Five of the activity questions were "patient-specific," which means that each patient identified and scored 5 activities in which the patient was limited by asthma; these 5 activities were identified at the first visit and retained for all subsequent follow-up visits.

      Positive change from baseline scores indicate improvement in quality of life.

    • Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 ]

      The ACQ is a 7-item instrument that measures asthma control (Juniper et al 1999). Six questions are self-assessments; the seventh item, completed by a member of the study staff, is the result of the patient's FEV1 measurement. Each item has 7 possible answers on a scale of 0 to 6, and the total score is the mean of all responses (the total scale is therefore 0-6). A higher score is an indication of poorer asthma control. The during treatment (Weeks 4, 8, 12 and 16) average ACQ was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.

      Negative change from baseline scores indicate improvement in asthma control.

    • Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE) [ Time Frame: Day 1 to Day 526 (longest treatment time plus 2 weeks) ]

      An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma:

      • use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids.
      • asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization.

      CAEs were adjudicated by committee to assure consistency. The distributions were compared by a log rank test stratified by baseline usage of oral corticosteroid (yes or no) and geographical region (US or other).

    • Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 ]

      The ASUI is an 11-item instrument designed to assess the frequency and severity of asthma symptoms and side effects, weighted by patient preferences (Revicki et al 1998). ASUI is a utility score that range

      Original Secondary Outcome:

      • Lung function as measured by Forced Expiratory Volume (FEV) and percent predicted Forced Expiratory Volume in 1 second (%FEV1)
      • Lung function as measured by Forced Vital Capacity (FVC)
      • Lung function as measured by Forced Expiratory Flow at 25% to 75% of FVC (FEF25-75%)
      • Measurement of time to first clinical asthma exacerbation (CAE)
      • Document the courses of oral corticosteroids prescribed for asthma worsening (3 or more days of administration or doubling of current dose)
      • Short-acting Beta-agonist usage [ Time Frame: during the entire 52 week treatment period ]
      • Blood eosinophil count [ Time Frame: from baseline to weeks 4,8,12,16,20,24,28,32,36,40,44,48, and 52 (or early withdrawal), or at time of first CAE ]
      • Asthma symptoms as measured by the Asthma Symptom Utility Index (ASUI)
      • Asthma control as measured by the Asthma Control Questionnaire (ACQ)
      • Quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ)
      • Safety and tolerability of reslizumab treatment in patients with eosinophilic asthma [ Time Frame: during the entire 52 week treatment period ]
      • Evaluate peak expiratory flow rate (PEFR), and characterize potential biomarkers in sputum [ Time Frame: During the entire 52 week treatment period ]


      Information By: Teva Pharmaceutical Industries

      Dates:
      Date Received: January 25, 2011
      Date Started: March 2011
      Date Completion:
      Last Updated: May 26, 2016
      Last Verified: May 2016