A Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations and Change in Lung Function in Patients (12-75 Years of Age) With Eosinophilic Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier:
NCT01287039
First received: January 28, 2011
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dosage study to evaluate the efficacy, safety, and immunogenicity of treatment with reslizumab in patients with eosinophilic asthma. The study consists of a 2- to 4-week screening period and a 52-week treatment period, including a final evaluation at week 52 (end-of-treatment visit; 4 weeks after the final infusion at week 48). After the end-of-treatment visit, patients will either enroll in an available open-label, long-term study or return for an assessment 90 (±7) days after their end-of-treatment visit in this study.


Condition Intervention Phase
Eosinophilic Asthma
Drug: Reslizumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 and Change in Lung Function in Patients (12-75 Years of Age) With Eosinophilic Asthma

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Change in forced expiratory volume (FEV1) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Frequency of clinical asthma exacerbations (CAE) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Lung function as measured by Forced Expiratory Volume (FEV1) [ Time Frame: From baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, or early withdrawal ] [ Designated as safety issue: No ]
  • Lung function as measured by percent predicted Forced Expiratory Volume in 1 second (%FEV1) [ Time Frame: From baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, or early withdrawal ] [ Designated as safety issue: No ]
  • Lung function as measured by Forced Vital Capacity (FVC) [ Time Frame: From baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, or early withdrawal ] [ Designated as safety issue: No ]
  • 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, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, or early withdrawal ] [ Designated as safety issue: No ]
  • Time to first clinical asthma exacerbation (CAE) [ Time Frame: From baseline through week 52 or early withdrawal ] [ Designated as safety issue: No ]
  • Courses of Oral Corticosteroids [ Time Frame: From baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, or early withdrawal ] [ Designated as safety issue: No ]
    Change in the number of 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: From baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32,36, 40,44,48, and 52, or early withdrawal ] [ Designated as safety issue: No ]
  • Blood eosinophil count [ Time Frame: From baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, or early withdrawal ] [ Designated as safety issue: No ]
  • Asthma Symptoms [ Time Frame: From baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or early withdrawal ] [ Designated as safety issue: No ]
    Asthma symptoms will be measured by the Asthma Symptom Utility Index (ASUI).

  • Asthma Control [ Time Frame: from baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or early withdrawal ] [ Designated as safety issue: No ]
    Asthma control will be measured by the Asthma Control Questionnaire (ACQ)

  • Quality of Life [ Time Frame: From baseline to weeks 16, 32, and 52, or early withdrawal ] [ Designated as safety issue: No ]
    Quality of life will be measured by the Asthma Quality of Life Questionnaire (AQLQ).

  • Immunogenicity [ Time Frame: From baseline and weeks 16, 32, 48, and 52 or early withdrawal ] [ Designated as safety issue: Yes ]
    Antibodies to reslizumab will be assessed. Blood samples for anti-reslizumab antibody assessment will also be obtained from all patients (inside and outside of the US) experiencing a serious adverse event, an adverse event leading to withdrawal, or an exacerbation of asthma symptoms.

  • Measurements of serum reslizumab concentrations [ Time Frame: Weeks 4, 8, 12, 16, 24, 36, and 48 ] [ Designated as safety issue: Yes ]
    Serum reslizumab concentrations will be collected to characterize the pharmacokinetics of reslizumab and to characterize the relationship between serum concentrations of reslizumab and measures of efficacy and safety.

  • Summary of Participants with Adverse Events [ Time Frame: From signing of the informed consent to Week 52 ] [ Designated as safety issue: Yes ]
    The safety and tolerability of reslizumab will be assessed throughout the study by evaluating adverse events, clinical laboratory tests, vital signs measurements, 12-lead ECGs, physical examinations (including body weight), and concomitant medication usage.


Enrollment: 489
Study Start Date: March 2011
Study Completion Date: April 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Reslizumab Drug: Reslizumab
3.0 mg/kg, administered intravenously (iv) once every 4 weeks over 52 weeks (a total of 13 doses administered)
Placebo Comparator: Placebo Drug: Placebo
Matching placebo (20 mM sodium acetate, 7% sucrose), administered intravenously (iv) once every 4 weeks over 52 weeks, for a total of 13 doses administered

  Eligibility

Ages Eligible for Study:   12 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma.
  • The patient has had at least 1 asthma exacerbation requiring oral, intramuscular (im), or intravenous (iv) corticosteroid use for at least 3 days over the past 12 months before screening.
  • The patient has a current blood eosinophil level of at least 400/μl.
  • The patient has airway reversibility of at least 12% to beta-agonist administration.
  • The patient has an ACQ score of at least 1.5 at the screening and baseline (before the 1st dose of study drug) visits.
  • The patient is taking inhaled fluticasone at a dosage of at least 440 μg, or equivalent, daily. Chronic oral corticosteroid use (no more than 10 mg/day prednisone or equivalent) is allowed. If a patient is on a stable dose, eg, 2 weeks or more of oral corticosteroid treatment at the time of study enrollment, the patient must remain on this dose throughout the study. The patient's baseline asthma therapy regimen (including but not limited to inhaled corticosteroids, oral corticosteroids up to a maximum of 10 mg of prednisone daily or equivalent, leukotriene antagonists, 5-lipooxygenase inhibitors, or cromolyn) must be stable for 30 days prior to screening and baseline, and must continue without dosage changes throughout study.
  • All female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test ß-human chorionic gonadotropin [ß-HCG]) at screening (serum) and baseline (urine).
  • Female patients of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study.
  • Written informed consent is obtained. Patients 12 through 17 years old must provide assent.
  • The patient is in reasonable health (except for diagnosis of asthma) as judged by the investigator, and as determined by a medical history, medical examination, ECG evaluation (at screening), serum chemistry, hematology, and urinalysis.

    • Other criteria apply; please contact the investigator for more information.

Exclusion Criteria:

  • The patient has a clinically meaningful co-morbidity that would interfere with the study schedule or procedures, or compromise the patient's safety.
  • The patient has known hypereosinophilic syndrome.
  • The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). Patients with pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis) will also be excluded.
  • The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).
  • The patient is using systemic immunosuppressive or immunomodulating or other biologic agents (including, but not limited to, anti-IgE mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor [anti TNF] mAb) within 6 months prior to screening.
  • The patient has previously received an anti-hIL-5 monoclonal antibody (eg, reslizumab, mepolizumab, or benralizumab).
  • The patient has any aggravating medical factors that are inadequately controlled (eg, rhinitis, gastroesophageal reflux disease, and uncontrolled diabetes).
  • The patient has participated in any investigative drug or device study within 30 days prior to screening.
  • The patient has participated in any investigative biologics study within 6 months prior to screening.
  • Female patients who are pregnant, nursing, or, if of childbearing potential, and not using a medically accepted, effective method of birth control (eg, barrier method with spermicide, abstinence, IUD, or steroidal contraceptive [oral, transdermal, implanted, and injected]) are excluded from this study. NOTE: Partner sterility alone is not considered an acceptable form of birth control.

    • Other criteria 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: NCT01287039

  Show 128 Study Locations
Sponsors and Collaborators
Cephalon
Investigators
Study Director: Sponsor's Medical Expert, Senior Director - Worldwide Clinical Research Cephalon
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier: NCT01287039     History of Changes
Other Study ID Numbers: C38072/3082
Study First Received: January 28, 2011
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
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
Hungary: National Institute of Pharmacy
Israel: Israeli Health Ministry Pharmaceutical Administration
Malaysia: Ministry of Health
New Zealand: Ministry of Health
Norway: Norwegian Medicines Agency
Philippines: Bureau of Food and Drugs
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Pharmacological Committee, Ministry of Health
South Africa: Medicines Control Council
Sweden: Medical Products Agency
Thailand: Food and Drug Administration

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 18, 2014