Clinical Trial: A Study to Evaluate the Efficacy and Safety of Reslizumab (0.3 or 3.0 mg/kg) as Treatment for Patients (12-75 Years of Age) With Eosinophilic Asthma

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

Official Title: A 16-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Reslizumab (0.3 or 3.0 mg/kg) as Treatment for Patients (12-75 Years of Age) With <

Brief Summary: The primary objective of this study is to determine whether reslizumab, at a dosage of 0.3 or 3.0 mg/kg administered once every 4 weeks for a total of 4 doses, is more effective than placebo in improving lung function in patients with eosinophilic asthma as assessed by the overall change from baseline in forced expiratory volume in 1 second (FEV1).

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

Current Primary Outcome: Change From Baseline In Forced Expiratory Volume In 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures [ Time Frame: Day 0 (baseline, pre-dose), Weeks 4, 8, 12 and 16 ]

Original Primary Outcome: Change in improvement in lung function as assessed by Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: baseline to week 16 (or early withdrawal) ]

Current Secondary Outcome:

• Change From Baseline in Forced Vital Capacity (FVC) Over 16 Weeks Using Mixed Model for Repeated Measures [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 ]
  The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters. The during treatment (weeks 4, 8, 12 and 16) average FVC 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 Forced Expiratory Flow at 25% to 75% Forced Vital Capacity (FEF 25%-75%) Over 16 Weeks Using Mixed Model for Repeated Measures [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 ]
  The FEF 25%-75% is the force expiratory flow at 25% to 75% of the Forced Vital Capacity (FVC). The during treatment (weeks 4, 8, 12 and 16) average FEF 25%-75% 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 % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint [ Time Frame: Day 1 (baseline, pre-dose), Week 16, endpoint ]
  The percent predicted FEV1 is the ratio of the volume of air expired in the first second of a forced expiration to the patient's predicted FEV based on a similar population without asthma. Endpoint =week 16 or early withdrawal.
• 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.

• Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) at Week 16 or at Last Observed Value [ Time Frame: Day 1 (baseline, pre-dose), Week 16 or last observed value ]

  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. The AQLQ score was only assessed once during the study at week 16 or at early withdrawal, i.e. last postbaseline assessment if within 3 to 5 weeks of the last dose of study drug.

• 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. 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.

• Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 ]

• Lung function as measured by percent predicted Forced Expiratory Volume in 1 second (%FEV1) [ Time Frame: from baseline to weeks 4, 8, 12, and 16 (or early withdrawal) ]
• Lung function as measured by Forced Vital Capacity (FVC) [ Time Frame: from baseline to weeks 4, 8, 12, and 16 (or early withdrawal) ]
• Lung function as measured by Forced Expiratory Flow at 25% to 75% of FVC (FEF25-75%) [ Time Frame: from baseline to weeks 4, 8, 12, and 16 (or early withdrawal) ]
• Beta-agonist use [ Time Frame: from baseline to weeks 4, 8, 12, and 16 (or early withdrawal) ]
• Blood eosinophil count [ Time Frame: from baseline to weeks 4, 8, 12, and 16 (or early withdrawal) ]
• Asthma symptoms as measured by the Asthma Symptom Utility Index (ASUI) [ Time Frame: from baseline to weeks 4, 8, 12, and 16 (or early withdrawal) ]
• Asthma control as measured by the Asthma Control Questionnaire (ACQ) [ Time Frame: from baseline to weeks 4, 8, 12, and 16 (or early withdrawal) ]
• Quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ) [ Time Frame: from baseline to week 16 (or early withdrawal) ]
• Evaluate the safety and tolerability of reslizumab treatment [ Time Frame: throughout the 2- to 4-week screening period and 16-week double-blind treatment period ]
  • occurrence of adverse events
  • clinical laboratory (serum chemistry, hematology, urinalysis) test results
  • vital signs (systolic and diastolic blood pressures, pulse, body temperature, and respiratory rate) measurements at weeks 4, 8, 12, and 16 or early withdrawal
  • physical examination findings, including body weight measurements, at weeks 4, 8, 12, and 16 or early withdrawal
  • 12-lead electrocardiography (ECG) findings at week 16 or early withdrawal
  • concomitant medication usage throughout the study
  • measurement of anti-drug antibodies at weeks 8 and 16 or early withdrawal

Dates:
Date Received: December 29, 2010
Date Started: February 2011
Date Completion:
Last Updated: April 28, 2016
Last Verified: April 2016