Study to Evaluate the Efficacy and Safety of Reslizumab Treatment in Patients With Moderate to Severe Asthma
- Registration Number
- NCT01508936
- Lead Sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 511
Not provided
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo intravenous injection every 4 weeks for a total of 4 doses. Reslizumab 3.0 mg/kg Reslizumab Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
- Primary Outcome Measures
Name Time Method Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in Full Analysis Set Baseline (Day 1), Week 16 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 was measured using forced expiratory air spirometry.
Data represent the slope estimate of change from baseline in FEV1 (measured in liters) at Week 16 versus baseline eosinophil count (measured in 10\^9/liter) by treatment group.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures Baseline (Day 1), Weeks 4, 8, 12, 16 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 was measured using forced expiratory air spirometry. Positive change from baseline scores indicate improvement in asthma control.
During study (Weeks 4, 8, 12 and 16) average value was calculated using a mixed effects model for repeated measures (MMRM) with treatment (reslizumab or placebo), blood eosinophil count at baseline, and the interaction of treatment and eosinophil count as a random effect.Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures Baseline (Day 1), Weeks 4, 8, 12, 16 The ACQ score was measured using the ACQ-7. Six questions are-self assessments; the seventh item is the result of the patient's % predicted 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 score of 0 indicates good asthma control; higher scores indicate increasingly poorer asthma control. Negative change from baseline scores indicate improvement in asthma control.
During study (Weeks 4, 8, 12 and 16) average value was calculated from mixed model repeated measures (MMRM) with treatment, visit, treatment by visit interaction, history of asthma exacerbation in the previous year, height, baseline value, and sex as fixed factors, and patient as a random effect.Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in FEV1 Subpopulation Baseline (Day 1), Week 16 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 was measured using forced expiratory air spirometry.
As with the primary outcome, data represent the slope estimate of change from baseline in FEV1 (measured in liters) at Week 16 versus baseline eosinophil count (measured in 10\^9/liter) by treatment group. However the FEV1 subpopulation includes participants with more impaired lung function (% predicted FEV1 \<85% at baseline).Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 4, 8, 12, and 16 Baseline (Day 1), Weeks 4, 8, 12, and 16 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 was measured using forced expiratory air spirometry. Positive change from baseline scores indicate improvement in asthma control.
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (% Predicted FEV1) at Weeks 4, 8, 12, 16 and Endpoint Baseline (Day 1), Weeks 4, 8, 12, and 16 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. Positive change from baseline scores indicate improvement in asthma control.
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 4, 8, 12, and 16 Baseline (Day 1), Weeks 4, 8, 12, and 16 The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters. FV was measured using forced expiratory air spirometry. Positive change from baseline scores indicate improvement in asthma control.
Change From Baseline in the Forced Expiratory Flow at 25% to 75% of the Forced Vital Capacity (FEF25%-75%) at Weeks 4, 8, 12, and 16 Baseline (Day 1), Weeks 4, 8, 12, and 16 The FEF25%-75% is the forced expiratory flow at 25% to 75% of the forced vital capacity. FEF25%-75% was measured using forced expiratory air spirometry. Positive change from baseline scores indicate improvement in asthma control.
Change From Baseline in Average Daily Use of Short-Acting Beta-Agonist Therapy (SABA) at Weeks 4, 8, 12, and 16 Baseline (Day -2 to 1), Weeks 4, 8, 12, and 16 SABA are used for quick relief of asthma symptoms. The number of times SABA therapy was used was assessed using 3 day recall at scheduled visits. Participants were asked to recall whether SABAs were used within 3 days of the scheduled visit and, if so, how many puffs were used. Daily use was the average of those 3 days. Negative change from baseline scores indicate improvement in asthma control.
Change From Baseline in Blood Eosinophil Counts at Weeks 4, 8, 12, 16, Follow-up (Week 28) and Endpoint Baseline (Day 1), Weeks 4, 8, 12, 16, Follow-up (Week 28) Blood eosinophil counts were measured using a standard complete blood count with differential blood test at each scheduled visit. Follow-up was performed approximately 12 weeks after the 16 week treatment period. Endpoint is the last post-baseline assessment.
Change From Baseline in Asthma Control Questionnaire (ACQ) at Weeks 4, 8, 12 and 16 Baseline (Day 1), Weeks 4, 8, 12 and 16 The ACQ score was measured using the ACQ-7. Six questions are self-assessments; the seventh item is the result of the patient's % predicted 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 score of 0 indicates good asthma control; higher scores indicate increasingly poorer asthma control. Negative change from baseline scores indicate improvement in asthma control.
Participants With Treatment-Emergent Adverse Events Day 1 to Week 28 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 Week 4 to Week 16 Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology, and urinalysis values during any of the lab tests conducted during the treatment period.
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\*ULN. Normal range is 4-49 U/L.
* Total bilirubin: \>=34.2 μmol/L
* Creatinine phosphokinase: \>5\*ULN. Normal range is 24-207 U/L.
* White blood cells: \<=3.0 or \>20 10\^9/L
* Hemoglobin: M\<=115, F\<=95 g/dL
* Hematocrit: M\<0.37, F\<0.32 L/L
* Platelets: \<=75 10\^9/L
* Absolute neutrophil count: \<=1.0 10\^9/L
* Urinalysis: blood, glucose, ketones and total protein: \>=2 unit increase from baselineParticipants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Week 4 to Week 28 Data represents participants with potentially clinically significant (PCS) vital sign values during any of the treatment period exams.
Significance criteria
* Heart rate - high: \>100 and increase of \>= 30 beats/minute (bpm)
* Sitting systolic blood pressure - high: \>160 and increase of \>=30 mmHg
* Sitting systolic blood pressure - low: \<90 and decrease of \>=30 mmHg
* Sitting diastolic blood pressure - high: \>100 and increase of \>=12 mmHg
* Sitting diastolic blood pressure - low: \<50 and decrease of \>=12 mmHg
* Body temperature - high: \>100.5° Fahrenheit or 38.1° Celsius and increase of \>2°
* Body temperature - low: \<96.5° Fahrenheit or \<35.8° CelsiusParticipants With Treatment-Emergent Potentially Clinically Significant (PCS) Electrocardiogram (ECG) Abnormalities Week 16 or endpoint Counts represent the number of participants with potentially clinically significant ECG abnormalities as assessed by the investigator.
Participants With a Positive Anti-Reslizumab Antibody Status During Study Screening (Week -3), Weeks 8 and 16 Counts of participants with a positive anti-drug antibody (ADA) response during treatment is offered for the experimental treatment arm. Blood samples were collected for determination of ADAs before study drug infusion at screening, weeks 8 and 16 or early withdrawal. Serum samples from patients who were treated with reslizumab were analyzed for ADA by Teva (Teva Biopharmaceuticals USA, Rockville, MD) using a validated homogeneous solution-based bridging enzyme-linked immunosorbent assay (ELISA).
Endpoint =week 16 or early withdrawal.
Counts represent the total number of participants at each time point with a positive immunogenicity test, and not 'new' participants with a positive test. An overall status of positive includes participants who had a positive ADA at any time point.
Trial Locations
- Locations (65)
Investigational Site 865
🇺🇸Miami, Florida, United States
Investigational Site 881
🇺🇸Miami, Florida, United States
Investigational Site 809
🇺🇸Tucson, Arizona, United States
Investigational Site 842
🇺🇸Homewood, Alabama, United States
Investigational Site 812
🇺🇸Rancho Mirage, California, United States
Investigational Site 837
🇺🇸Centennial, Colorado, United States
Investigational Site 805
🇺🇸Albany, Georgia, United States
Investigational Site 855
🇺🇸Jacksonville, Florida, United States
Investigational Site 870
🇺🇸Stockbridge, Georgia, United States
Investigational Site 883
🇺🇸Evansville, Indiana, United States
Investigational Site 816
🇺🇸Chicago, Illinois, United States
Investigational Site 824
🇺🇸Shiloh, Illinois, United States
Investigational Site 873
🇺🇸Owensboro, Kentucky, United States
Investigational Site 889
🇺🇸Troy, Michigan, United States
Investigational Site 871
🇺🇸Fall River, Massachusetts, United States
Investigational Site 841
🇺🇸St. Louis, Missouri, United States
Investigational Site 834
🇺🇸North Dartmouth, Massachusetts, United States
Investigational Site 880
🇺🇸Dallas, Texas, United States
Investigational Site 858
🇺🇸Dickinson, Texas, United States
Investigational Site 867
🇺🇸Seattle, Washington, United States
Investigational Site 823
🇺🇸LaCrosse, Wisconsin, United States
Investigational Site 803
🇺🇸Nashville, Tennessee, United States
Investigational Site 892
🇺🇸Tucson, Arizona, United States
Investigational Site 852
🇺🇸Los Angeles, California, United States
Investigational Site 846
🇺🇸Little Rock, Arkansas, United States
Investigational Site 864
🇺🇸Newport Beach, California, United States
Investigational Site 887
🇺🇸Jasper, Alabama, United States
Investigational Site 862
🇺🇸Huntington Beach, California, United States
Investigational Site 828
🇺🇸Anaheim, California, United States
Investigational Site 900
🇺🇸Fresno, California, United States
Investigational Site 832
🇺🇸Wheat Ridge, Colorado, United States
Investigational Site 820
🇺🇸Lenexa, Kansas, United States
Investigational Site 875
🇺🇸White Marsh, Maryland, United States
Investigational Site 801
🇺🇸Lafayette, Louisiana, United States
Investigational Site 877
🇺🇸Mandeville, Louisiana, United States
Investigational Site 818
🇺🇸St. Louis, Missouri, United States
Investigational Site 878
🇺🇸Fort Wayne, Indiana, United States
Investigational Site 814
🇺🇸Orangeburg, South Carolina, United States
Investigational Site 810
🇺🇸Tulsa, Oklahoma, United States
Investigational Site 854
🇺🇸Jenkintown, Pennsylvania, United States
Investigational Site 838
🇺🇸Rolla, Missouri, United States
Investigational Site 857
🇺🇸Albuquerque, New Mexico, United States
Investigational Site 836
🇺🇸Richmond, Virginia, United States
Investigational Site 844
🇺🇸Charlotte, North Carolina, United States
Investigational Site 833
🇺🇸Spokane, Washington, United States
Investigational Site 802
🇺🇸Florence, South Carolina, United States
Investigational Site 876
🇺🇸West Jordan, Utah, United States
Investigational Site 821
🇺🇸Spartanburg, South Carolina, United States
Investigational Site 845
🇺🇸Middleburg Heights, Ohio, United States
Investigational Site 843
🇺🇸Providence, Rhode Island, United States
Investigational Site 829
🇺🇸Spartanburg, South Carolina, United States
Investigational Site 850
🇺🇸Knoxville, Tennessee, United States
Investigational Site 847
🇺🇸Salt Lake City, Utah, United States
Investigational Site 879
🇺🇸Plano, Texas, United States
Investigational Site 904
🇺🇸Vancouver, Washington, United States
Investigational Site 869
🇺🇸Live Oak, Texas, United States
Investigational Site 840
🇺🇸Fairfax, Virginia, United States
Investigational Site 806
🇺🇸Greenfield, Wisconsin, United States
Investigational Site 909
🇺🇸Los Angeles, California, United States
Investigational Site 808
🇺🇸Riverside, California, United States
Investigational Site 819
🇺🇸Newburgh, New York, United States
Investigational Site 861
🇺🇸Birmingham, Alabama, United States
Investigational Site 804
🇺🇸Sacramento, California, United States
Investigational Site 851
🇺🇸Denver, Colorado, United States
Investigational Site 859
🇺🇸Portland, Oregon, United States