Clinical Trial: A Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in Patients (12-75 Years of Age) 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: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and immunogenicity of treatment with reslizumab in patients with eosinophilic asthma.

Detailed Summary:

Demonstrate the efficacy of reslizumab, at a dose of 3 mg/kg administered iv every 4 weeks over 12 months, as assessed by the reduction in frequency of clinical asthma exacerbations (CAEs) during 12 months.

An exacerbation event will be considered a CAE if the patient meets either or both of the criteria listed below and this is 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
  • asthma-related emergency treatment The above criteria must be corroborated with at least 1 other measurement to indicate worsening in the clinical signs and symptoms of asthma.

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 Week 52 ]

    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 Week 52 ]

    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:

    • A reduction in the frequency (i.e., number) of clinical asthma exacerbations (CAEs) [ Time Frame: during the full treatment period of 52 weeks ]
    • Overall change in forced expiratory volume in 1 second (FEV1) [ Time Frame: From baseline to Week 16, or the onset of first CAE, whichever occurs first ]


    Current Secondary Outcome:

    • 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. Positive change from baseline scores indicate improvement in asthma control.

      The during treatment (Weeks 4, 8, 12 and 16) average FEV1 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.

    • 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 478 (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 ranges from 0 to 1, with higher values indicating better asthma control; info obtained from questionnaire about asthma symptoms.

      The during treatment (Weeks 4, 8, 12 and 16) average ASUI 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.

      Positive change from baseline values indicate improvement in asthma symptoms. Information was obtained from questionnaire about asthma symptoms.

      Original Secondary Outcome:

      • Lung function as measured by Forced Expiratory Volume (FEV1)
      • Lung function as measured by 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
      • 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 ]


      Information By: Teva Pharmaceutical Industries

      Dates:
      Date Received: January 28, 2011
      Date Started: April 2011
      Date Completion:
      Last Updated: May 26, 2016
      Last Verified: May 2016