Clinical Trial: Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Reslizumab (3.0 mg/kg) as Treatment for Patients (12 Through 75 Years of Age) With Eosinophilic Asthma

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Reslizumab (3.0 mg/kg) as Treatment for Patients With Eosinophilic Asthma Who Completed a Pr

Brief Summary: The primary objective of the study is to evaluate the long-term safety of reslizumab at a dosage of 3.0 mg/kg every 4 weeks for approximately 24 months in pediatric and adult patients with eosinophilic asthma as assessed by adverse events, physical examination findings, vital sign measurements, and concomitant medication usage throughout the study (every 4 weeks), clinical laboratory test results, and measurement of antidrug antibodies.

Detailed Summary:

Study patients deemed eligible based on activities from the preceding Teva sponsored double blind study of reslizumab in eosinophilic asthma. Specifically, as per inclusion criterion c, patients must have either completed treatment in a previous Teva-sponsored study or have received at least 2 doses of study drug treatment in a pulmonary function study.

Eligible patients could enroll in this study only after completion of the end of treatment visit in a Teva sponsored, randomized, placebo controlled, double blind study of reslizumab in eosinophilic asthma, which served as the screening/baseline visit for participation in this open label extension study. The use of systemic corticosteroids for asthma in any of the previous Teva sponsored double blind studies of reslizumab did not exclude patients from this study. The previous Teva studies were C38072/3081 (NCT01270464), C38072/3082 (NCT01287039), and C38072/3083 (NCT01285323).


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

Current Primary Outcome:

  • Participants With Treatment-Emergent Adverse Events [ Time Frame: Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit. ]
    An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
  • Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values [ Time Frame: Weeks 4, 8, 24 and 48 ]

    Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology, and urinalysis values on any of the during treatment lab analyses.

    Significance criteria:

    • Blood urea nitrogen: >=10.71 mmol/L
    • Creatinine: >=177 μmol/L
    • Uric acid: M>=625, F>=506 μmol/L
    • Aspartate amin

      Original Primary Outcome: Evaluate the Long-Term Safety of Reslizumab administration

      - as assessed by adverse events, physical examination findings, vital sign measurements, concomitant medication usage, clinical laboratory test results, and measurement of antidrug antibodies


      Current Secondary Outcome:

      • Forced Expiratory Volume In 1 Second (FEV1) at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, End of Study and Endpoint [ Time Frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint ]
        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.
      • Percent Predicted Forced Expiratory Volume In 1 Second (% Predicted FEV1) at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, End of Study and Endpoint [ Time Frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and 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. Percent predicted lung function values were transcribed directly from the lung function report to the CRF, without any calculation by Teva.
      • Forced Vital Capacity (FVC) at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, End of Study and Endpoint [ Time Frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint ]

        The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters.

      • Forced Expiratory Flow at 25% to 75% Forced Vital Capacity (FEF 25%-75%) at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, End of Study and Endpoint [ Time Frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint ]

        The FEF 25%-75% is the force expiratory flow at 25% to 75% of the Forced Vital Capacity (FVC), measured in liters/second

      • Average Daily Use of Short-Acting Beta-Agonist (SABA)Therapy at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, End of Study and Endpoint [ Time Frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint ]

        SABA are used for quick relief of asthma symptoms. To measure SABA use, at each clinical visit participants were asked to recall their usage of SABA therapy within the last 3 days of the scheduled visit. If usage was confirmed, the number of puffs used was recorded. For the purpose of summaries, an average daily usage was evaluated by dividing the total number of puffs recorded over 3 days by 3.

      • Asthma Symptom Utility Index (ASUI) Score at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, End of Study and Endpoint [ Time Frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint ]

        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.

      • Asthma Control Questionnaire (ACQ) at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, End of Study and Endpoint [ Time Frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint ]
        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.
      • Asthma Quality of Life Questionnaire (AQLQ) Total Score at Weeks 24, 48, 72, 96, End of Study and Endpoint [ Time Frame: Weeks 24, 48, 72, 96, End of Study and Endpoint ]
        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.
      • Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Weeks 24, 48, 72, 96, End of Study, Endpoint and Overall [ Time Frame: Baseline, Weeks 24, 48, 72, 96, End of Study, Endpoint and Overall ]

        Blood samples were collected for the determination of anti-drug antibody (ADAs) before study drug infusion at baseline and every 24 weeks until end of treatment visit or early withdrawal. Serum samples were analyzed by Teva (Teva Biopharmaceuticals USA, Rockville, Maryland, USA) usi

        Original Secondary Outcome:

        • Lung function as measured by Forced Expiratory Volume in 1 second (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% FVC (FEF25-75%)
        • Short-acting Beta-agonist usage
        • 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)


        Information By: Teva Pharmaceutical Industries

        Dates:
        Date Received: February 4, 2011
        Date Started: June 2011
        Date Completion:
        Last Updated: April 28, 2016
        Last Verified: April 2016