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

This study has been terminated.
(Business decision)
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier:
NCT01290887
First received: February 4, 2011
Last updated: April 28, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Eosinophilic Asthma
Drug: Reslizumab
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Prior Teva-Sponsored Study in Eosinophilic Asthma

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

    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 aminotransferase: >=3*upper limit of normal (ULN). Normal range is 10-43 U/L
    • Alanine aminotransferase: >=3*ULN. Normal range is 10-40 U/L
    • GGT = gamma-glutamyl transpeptidase: >= 3*upper limit of normal. Normal range is 5-49 U/L.
    • Total bilirubin: >=34.2 μmol/L
    • White blood cells- low: <=3.0*10^9/L
    • White blood cells-high: >=20*10^9/L
    • Hemoglobin: M<=115, F<=95 g/dL
    • Hematocrit: M<0.37, F<0.32 L/L
    • Platelets: >=700*10^9/L
    • Absolute neutrophil count: <=1.0*10^9/L
    • Eosinophils: >=10
    • Urinalysis: ketones, blood, glucose, and total protein: >=2 unit increase from baseline

  • Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values [ Time Frame: Week 4 to Week 65 ] [ Designated as safety issue: Yes ]

    Data represents participants with PCS vital sign values during any of the during treatment visits or the follow-up visit.

    Significance criteria

    • Sitting heart rate-high: >100 and increase of >= 30 beats/min (all ages)
    • Sitting heart rate-low: <50 and decrease of >=30 beats/min
    • Sitting systolic blood pressure (BP)-high: >130 and increase of >=30 mmHg (ages 12-17)
    • Systolic BP-low: <90 and decrease of >=30 mmHg (ages >=18)
    • Systolic BP-high: >160 and increase of >=30 mmHg (ages >=18)
    • Sitting diastolic BP-low: <55 and decrease of >=12 mmHg (ages 12-17)
    • Diastolic BP-high: >85 and increase of >=12 mmHg (ages 12-17)
    • Diastolic BP-low: <50 and decrease of >=12 mmHg (ages >=18)
    • Diastolic BP-high: >100 and increase of >=12 mmHg (ages >=18)
    • Respiration rate: >20 and increase of >=10 breaths/minute (ages 12-17)
    • Respiration rate: >24 and increase of >=10 breaths/minute (ages >=18)
    • Body temperature-low: <96.5° Fahrenheit (all ages)
    • Body temp-high: >100.5° F (all ages)


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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) using a validated homogeneous solution based bridging enzyme linked immune sorbent assay (Mikulsis et al 2011, Qui et al 2010). The analysis of anti-reslizumab antibody in patient serum consists of 3 tiers of assays for screening, confirmation, and titer analysis. If a participant had a treatment-emergent ADA response (ie, ADA positive at any of the postdose time points but negative at the predose time point) or if there was a treatment-boosted ADA response (defined as a greater than 4-fold increase from a positive baseline ADA response (Shankar et at 2014), the participant was classified as overall ADA positive.

    Predose samples for the reslizumab-experienced participants came from the previous studies.



Enrollment: 1052
Study Start Date: June 2011
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Reslizumab 3.0 mg/kg
Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for up to 24 months.
Drug: Reslizumab
Reslizumab (3.0 mg/kg) administered intravenously by infusion every 28 days (±7 days), for approximately 24 months
Other Names:
  • Cinquil
  • humanized monoclonal antibody
  • CEP-38072

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   12 Years to 75 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent is obtained.
  • Patient must have completed treatment in a previous Cephalon-sponsored double-blind asthma exacerbation study or received at least 2 doses of study drug treatment in a pulmonary function study.
  • The patient must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and willing to return to the clinic for the follow-up evaluation as specified in this protocol.
  • other criteria may apply; please contact the investigator for more information.

Exclusion Criteria:

  • The patient has a clinically meaningful comorbidity that would interfere with the study schedule or procedures, or compromise the patient's safety.
  • The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer).
  • The patient is a current smoker.
  • The patient is expected to be poorly compliant with study drug administration, study procedures, or visits.
  • The patient has any aggravating factors that are inadequately controlled (e.g., gastroesophageal reflux disease [GERD]).
  • Female patients who are pregnant, or nursing, or, if of childbearing potential and not using a medically accepted, effective method of birth control (eg, spermicide, abstinence, intrauterine device [IUD], or steroidal contraceptive [oral, transdermal, implanted, and injected] in conjunction with a barrier method) are excluded from this study.
  • The patient has a current infection or disease that may preclude assessment of asthma.
  • other criteria may apply; please contact the investigator for more information.
  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: NCT01290887

  Show 219 Study Locations
Sponsors and Collaborators
Teva Branded Pharmaceutical Products, R&D Inc.
Investigators
Study Director: Sponsor's Medical Expert, Senior Director - Worldwide Clinical Research Cephalon
  More Information

Responsible Party: Teva Branded Pharmaceutical Products, R&D Inc.
ClinicalTrials.gov Identifier: NCT01290887     History of Changes
Other Study ID Numbers: C38072/3085  2010-024540-15 
Study First Received: February 4, 2011
Results First Received: March 23, 2016
Last Updated: April 28, 2016
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belarus: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Canada: Health Canada
Chile: Ministry of Health
Colombia: National Institutes of Health
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ministry of Health
Greece: Ministry of Health and Welfare
Hungary: National Institute of Pharmacy
India: Ministry of Health
Israel: Israeli Health Ministry Pharmaceutical Administration
Malaysia: Ministry of Health
Mexico: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
New Zealand: Ministry of Health
Norway: Norwegian Medicines Agency
Peru: Ministry of Health
Philippines: Bureau of Food and Drugs
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Sweden: Medical Products Agency
Thailand: Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health

Additional relevant MeSH terms:
Asthma
Pulmonary Eosinophilia
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Hypereosinophilic Syndrome
Eosinophilia
Leukocyte Disorders
Hematologic Diseases

ClinicalTrials.gov processed this record on August 25, 2016