Study to Evaluate the Efficacy and Safety of Reslizumab Treatment in Patients With Moderate to Severe Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier:
NCT01508936
First received: January 3, 2012
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

The primary objective of the study is to characterize the efficacy of reslizumab treatment, at a dosage of 3.0 milligrams per kilogram (mg/kg) every 4 weeks for a total of 4 doses, in improving pulmonary function in relation to baseline blood eosinophil levels in patients with moderate to severe asthma, as assessed by the change from baseline to week 16 in forced expiratory volume in 1 second (FEV1).


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) Treatment in Patients With Moderate to Severe Asthma

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Change in Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 will be measured using forced expiratory air spirometry. Standard methods for this measurement are widely accepted in clinical practice.


Secondary Outcome Measures:
  • Change in FEV1 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 will be measured using forced expiratory air spirometry. Standard methods for this measurement are widely accepted in clinical practice.

  • Change in FEV1 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 will be measured using forced expiratory air spirometry. Standard methods for this measurement are widely accepted in clinical practice.

  • Change in FEV1 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 will be measured using forced expiratory air spirometry. Standard methods for this measurement are widely accepted in clinical practice.

  • Change in Percent Predicted FEV1 [ Time Frame: Baseline and Week 4 ] [ 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 forced vital capacity (FVC).

  • Change in Percent Predicted FEV1 [ Time Frame: Baseline and Week 8 ] [ 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 FVC.

  • Change in Percent Predicted FEV1 [ Time Frame: Baseline and Week 12 ] [ 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 FVC.

  • Change in Percent Predicted FEV1 [ Time Frame: Baseline and Week 16 ] [ 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 FVC.

  • Change in Forced Vital Capacity (FVC) [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters.

  • Change in Forced Vital Capacity (FVC) [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters.

  • Change in Forced Vital Capacity (FVC) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters.

  • Change in Forced Vital Capacity (FVC) [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters.

  • Change in Forced Expiratory Flow Rate (FEF) 25-75% [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    FEF 25-75% is the average forced expiratory flow rate during the middle portion of expiration.

  • Change in Forced Expiratory Flow Rate (FEF) 25-75% [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    FEF 25-75% is the average forced expiratory flow rate during the middle portion of expiration.

  • Change in Forced Expiratory Flow Rate (FEF) 25-75% [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    FEF 25-75% is the average forced expiratory flow rate during the middle portion of expiration.

  • Change in Forced Expiratory Flow Rate (FEF) 25-75% [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    FEF 25-75% is the average forced expiratory flow rate during the middle portion of expiration.

  • Change in Beta-agonist use [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    The number of times a beta-agonist therapy is used will be assessed using 3-day recall at scheduled visits. Patients will be asked to recall date and time of any use of beta-agonist therapy, name of medicine, and number of puffs inhaled.

  • Change in Beta-agonist use [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The number of times a beta-agonist therapy is used will be assessed using 3-day recall at scheduled visits. Patients will be asked to recall date and time of any use of beta-agonist therapy, name of medicine, and number of puffs inhaled.

  • Change in Beta-agonist use [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The number of times a beta-agonist therapy is used will be assessed using 3-day recall at scheduled visits. Patients will be asked to recall date and time of any use of beta-agonist therapy, name of medicine, and number of puffs inhaled.

  • Change in Beta-agonist use [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The number of times a beta-agonist therapy is used will be assessed using 3-day recall at scheduled visits. Patients will be asked to recall date and time of any use of beta-agonist therapy, name of medicine, and number of puffs inhaled.

  • Change in blood eosinophil count [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    The blood eosinophil counts will be measured using a standard complete blood count (CBC) with differential blood test. The results of the differential will be blinded.

  • Change in blood eosinophil count [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The blood eosinophil counts will be measured using a standard complete blood count (CBC) with differential blood test. The results of the differential will be blinded.

  • Change in blood eosinophil count [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The blood eosinophil counts will be measured using a standard complete blood count (CBC) with differential blood test. The results of the differential will be blinded.

  • Change in blood eosinophil count [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The blood eosinophil counts will be measured using a standard complete blood count (CBC) with differential blood test. The results of the differential will be blinded.

  • Change in blood eosinophil count [ Time Frame: Baseline and 12 weeks after end of treatment (EOT) or early withdrawal ] [ Designated as safety issue: No ]
    The blood eosinophil counts will be measured using a standard complete blood count (CBC) with differential blood test. The results of the differential will be blinded.

  • Change in Asthma Control Questionnaire (ACQ) Score [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    The ACQ is a validated asthma assessment tool that has been widely used. Six questions are self assessments; the seventh item is the result of the patient's FEV1 measurement. Each item on the ACQ has a possible score ranging from 0 (indicating that the asthma is well controlled) to 6 (indicating that the asthma is severely uncontrolled), and the total score is the mean of all responses.

  • Change in Asthma Control Questionnaire (ACQ) Score [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The ACQ is a validated asthma assessment tool that has been widely used. Six questions are self assessments; the seventh item is the result of the patient's FEV1 measurement. Each item on the ACQ has a possible score ranging from 0 (indicating that the asthma is well controlled) to 6 (indicating that the asthma is severely uncontrolled), and the total score is the mean of all responses.

  • Change in Asthma Control Questionnaire (ACQ) Score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The ACQ is a validated asthma assessment tool that has been widely used. Six questions are self assessments; the seventh item is the result of the patient's FEV1 measurement. Each item on the ACQ has a possible score ranging from 0 (indicating that the asthma is well controlled) to 6 (indicating that the asthma is severely uncontrolled), and the total score is the mean of all responses.

  • Change in Asthma Control Questionnaire (ACQ) Score [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The ACQ is a validated asthma assessment tool that has been widely used. Six questions are self assessments; the seventh item is the result of the patient's FEV1 measurement. Each item on the ACQ has a possible score ranging from 0 (indicating that the asthma is well controlled) to 6 (indicating that the asthma is severely uncontrolled), and the total score is the mean of all responses.

  • Summary of participants with Adverse Events [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 510
Study Start Date: January 2012
Study Completion Date: October 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Reslizumab Drug: Reslizumab
Reslizumab will be administered to patients at a dosage of 3.0 mg/kg by intravenous (iv) infusion by qualified study personnel every 4 weeks for 16 weeks (for a total of 4 doses).
Placebo Comparator: Placebo Drug: Matching Placebo
Matching placebo will be administered every 4 weeks for 16 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Patients are included in the study if all of the following criteria are met:

  • The patient is a man or woman, 18 through 65 years of age, with a diagnosis of asthma.
  • The patient has an ACQ score of at least 1.5.
  • At screening, the patient has airway reversibility of at least 12% to beta-agonist administration.
  • The patient is currently taking fluticasone at a dosage of at least 440 µg daily (or equivalent). Patients' baseline asthma therapy regimens (including but not limited to inhaled corticosteroids, leukotriene antagonists, 5-lipoxygenase inhibitors, cromolyn) must be stable for 30 days before screening and continue without dosage changes throughout study.
  • Female patients must be surgically sterile, 2 years postmenopausal, or must have a negative beta-human chorionic gonadotropin (ßHCG) result for a pregnancy test 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. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected).
  • Written informed consent is obtained.
  • 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, electrocardiogram (ECG) evaluation, serum chemistry, hematology, urinalysis, and serology.
  • 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 be willing to return to the clinic for the follow-up evaluation as specified in this protocol.

Exclusion Criteria:

Patients are excluded from participating in this study if 1 or more of the following criteria are met:

  • The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer). The patient has other pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis).
  • 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 known hypereosinophilic syndrome (HES).
  • The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).
  • The patient has a history of use of systemic immunosuppressive or immunomodulating agents (anti-immunoglobulin E [anti-IgE] mAb, methotrexate, cyclosporin, interferon-α, anti-tumor necrosis factor mAb, or omalizumab) within 6 months prior to study entry (randomization).
  • The patient is currently using or has used systemic corticosteroids (includes use of oral corticosteroids) within 30 days prior to the screening visit.
  • 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, and thus would aggravate asthma symptoms (eg, gastroesophageal reflux disease).
  • 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 90 days prior to screening.
  • The patient has previously received reslizumab or other anti-hIL-5 mAbs (eg, mepolizumab).
  • The patient is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
  • The patient has a current infection or disease that may preclude assessment of asthma.
  • The patient has a history of concurrent immunodeficiency (human immunodeficiency, acquired immunodeficiency syndrome, or congenital immunodeficiency).
  • The patient is suspected of current drug or alcohol abuse as specified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
  • The patient has presence of or suspected parasitic infestation/infection.
  • Patients may not have received any live attenuated vaccine within the 12-week period before study entry.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01508936

  Hide Study Locations
Locations
United States, Alabama
Investigational Site 861
Birmingham, Alabama, United States
Investigational Site 842
Homewood, Alabama, United States
Investigational Site 887
Jasper, Alabama, United States
United States, Arizona
Investigational Site 809
Tucson, Arizona, United States
Investigational Site 892
Tucson, Arizona, United States
United States, Arkansas
Investigational Site 846
Little Rock, Arkansas, United States
United States, California
Investigational Site 828
Anaheim, California, United States
Investigational Site 900
Fresno, California, United States
Investigational Site 862
Huntington Beach, California, United States
Investigational Site 852
Los Angeles, California, United States
Investigational Site 909
Los Angeles, California, United States
Investigational Site 864
Newport Beach, California, United States
Investigational Site 812
Rancho Mirage, California, United States
Investigational Site 808
Riverside, California, United States
Investigational Site 804
Sacramento, California, United States
United States, Colorado
Investigational Site 837
Centennial, Colorado, United States
Investigational Site 851
Denver, Colorado, United States
Investigational Site 832
Wheat Ridge, Colorado, United States
United States, Florida
Investigational Site 855
Jacksonville, Florida, United States
Investigational Site 865
Miami, Florida, United States
Investigational Site 881
Miami, Florida, United States
United States, Georgia
Investigational Site 805
Albany, Georgia, United States
Investigational Site 870
Stockbridge, Georgia, United States
United States, Illinois
Investigational Site 816
Chicago, Illinois, United States
Investigational Site 824
Shiloh, Illinois, United States
United States, Indiana
Investigational Site 883
Evansville, Indiana, United States
Investigational Site 878
Fort Wayne, Indiana, United States
United States, Kansas
Investigational Site 820
Lenexa, Kansas, United States
United States, Kentucky
Investigational Site 873
Owensboro, Kentucky, United States
United States, Louisiana
Investigational Site 801
Lafayette, Louisiana, United States
Investigational Site 877
Mandeville, Louisiana, United States
United States, Maryland
Investigational Site 875
White Marsh, Maryland, United States
United States, Massachusetts
Investigational Site 871
Fall River, Massachusetts, United States
Investigational Site 834
North Dartmouth, Massachusetts, United States
United States, Michigan
Investigational Site 889
Troy, Michigan, United States
United States, Missouri
Investigational Site 838
Rolla, Missouri, United States
Investigational Site 818
St. Louis, Missouri, United States
Investigational Site 841
St. Louis, Missouri, United States
United States, New Mexico
Investigational Site 857
Albuquerque, New Mexico, United States
United States, New York
Investigational Site 819
Newburgh, New York, United States
United States, North Carolina
Investigational Site 844
Charlotte, North Carolina, United States
United States, Ohio
Investigational Site 845
Middleburg Heights, Ohio, United States
United States, Oklahoma
Investigational Site 810
Tulsa, Oklahoma, United States
United States, Oregon
Investigational Site 859
Ashland, Oregon, United States
Investigational Site 859
Portland, Oregon, United States
United States, Pennsylvania
Investigational Site 854
Jenkintown, Pennsylvania, United States
United States, Rhode Island
Investigational Site 843
Providence, Rhode Island, United States
United States, South Carolina
Investigational Site 802
Florence, South Carolina, United States
Investigational Site 814
Orangeburg, South Carolina, United States
Investigational Site 821
Spartanburg, South Carolina, United States
Investigational Site 829
Spartanburg, South Carolina, United States
United States, Tennessee
Investigational Site 850
Knoxville, Tennessee, United States
Investigational Site 803
Nashville, Tennessee, United States
United States, Texas
Investigational Site 880
Dallas, Texas, United States
Investigational Site 858
Dickinson, Texas, United States
Investigational Site 869
Live Oak, Texas, United States
Investigational Site 879
Plano, Texas, United States
United States, Utah
Investigational Site 847
Salt Lake City, Utah, United States
Investigational Site 876
West Jordan, Utah, United States
United States, Virginia
Investigational Site 840
Fairfax, Virginia, United States
Investigational Site 836
Richmond, Virginia, United States
United States, Washington
Investigational Site 867
Seattle, Washington, United States
Investigational Site 833
Spokane, Washington, United States
Investigational Site 904
Vancouver, Washington, United States
United States, Wisconsin
Investigational Site 806
Greenfield, Wisconsin, United States
Investigational Site 823
LaCrosse, Wisconsin, United States
Sponsors and Collaborators
Teva Pharmaceutical Industries
Investigators
Study Director: Global Respiratory Clinical Research, M.D. Sponsor's Medical Expert
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier: NCT01508936     History of Changes
Other Study ID Numbers: C38072/3084
Study First Received: January 3, 2012
Last Updated: November 13, 2013
Health Authority: United States: 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 April 17, 2014