Back to resultsStudy to Evaluate the Efficacy and Safety of Reslizumab Treatment in Patients With Moderate to Severe Asthma
Primary Purpose
Eosinophilic Asthma
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Reslizumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Eosinophilic Asthma
Eligibility 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.
Sites / Locations
- Investigational Site 861
- Investigational Site 842
- Investigational Site 887
- Investigational Site 809
- Investigational Site 892
- Investigational Site 846
- Investigational Site 828
- Investigational Site 900
- Investigational Site 862
- Investigational Site 852
- Investigational Site 909
- Investigational Site 864
- Investigational Site 812
- Investigational Site 808
- Investigational Site 804
- Investigational Site 837
- Investigational Site 851
- Investigational Site 832
- Investigational Site 855
- Investigational Site 865
- Investigational Site 881
- Investigational Site 805
- Investigational Site 870
- Investigational Site 816
- Investigational Site 824
- Investigational Site 883
- Investigational Site 878
- Investigational Site 820
- Investigational Site 873
- Investigational Site 801
- Investigational Site 877
- Investigational Site 875
- Investigational Site 871
- Investigational Site 834
- Investigational Site 889
- Investigational Site 838
- Investigational Site 818
- Investigational Site 841
- Investigational Site 857
- Investigational Site 819
- Investigational Site 844
- Investigational Site 845
- Investigational Site 810
- Investigational Site 859
- Investigational Site 859
- Investigational Site 854
- Investigational Site 843
- Investigational Site 802
- Investigational Site 814
- Investigational Site 821
- Investigational Site 829
- Investigational Site 850
- Investigational Site 803
- Investigational Site 880
- Investigational Site 858
- Investigational Site 869
- Investigational Site 879
- Investigational Site 847
- Investigational Site 876
- Investigational Site 840
- Investigational Site 836
- Investigational Site 867
- Investigational Site 833
- Investigational Site 904
- Investigational Site 806
- Investigational Site 823
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Reslizumab 3.0 mg/kg
Arm Description
Placebo intravenous injection every 4 weeks for a total of 4 doses.
Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Outcomes
Primary Outcome Measures
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in Full Analysis Set
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
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures
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
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
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
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
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
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
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
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
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
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
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
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 baseline
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values
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° Celsius
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Electrocardiogram (ECG) Abnormalities
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
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.
Full Information
NCT ID
NCT01508936
First Posted
January 3, 2012
Last Updated
May 26, 2016
Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01508936
Brief Title
Study to Evaluate the Efficacy and Safety of Reslizumab Treatment in Patients With Moderate to Severe Asthma
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Eosinophilic Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
511 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo intravenous injection every 4 weeks for a total of 4 doses.
Arm Title
Reslizumab 3.0 mg/kg
Arm Type
Experimental
Arm Description
Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Intervention Type
Drug
Intervention Name(s)
Reslizumab
Other Intervention Name(s)
Cinquil, humanized monoclonal antibody, CEP-38072
Intervention Description
Reslizumab administered 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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo administered by intravenous (iv) infusion by qualified study personnel every 4 weeks for 16 weeks (for a total of 4 doses).
Primary Outcome Measure Information:
Title
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in Full Analysis Set
Description
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.
Time Frame
Baseline (Day 1), Week 16
Secondary Outcome Measure Information:
Title
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures
Description
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.
Time Frame
Baseline (Day 1), Weeks 4, 8, 12, 16
Title
Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures
Description
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.
Time Frame
Baseline (Day 1), Weeks 4, 8, 12, 16
Title
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in FEV1 Subpopulation
Description
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).
Time Frame
Baseline (Day 1), Week 16
Title
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 4, 8, 12, and 16
Description
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.
Time Frame
Baseline (Day 1), Weeks 4, 8, 12, and 16
Title
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (% Predicted FEV1) at Weeks 4, 8, 12, 16 and Endpoint
Description
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.
Time Frame
Baseline (Day 1), Weeks 4, 8, 12, and 16
Title
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 4, 8, 12, and 16
Description
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.
Time Frame
Baseline (Day 1), Weeks 4, 8, 12, and 16
Title
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
Description
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.
Time Frame
Baseline (Day 1), Weeks 4, 8, 12, and 16
Title
Change From Baseline in Average Daily Use of Short-Acting Beta-Agonist Therapy (SABA) at Weeks 4, 8, 12, and 16
Description
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.
Time Frame
Baseline (Day -2 to 1), Weeks 4, 8, 12, and 16
Title
Change From Baseline in Blood Eosinophil Counts at Weeks 4, 8, 12, 16, Follow-up (Week 28) and Endpoint
Description
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.
Time Frame
Baseline (Day 1), Weeks 4, 8, 12, 16, Follow-up (Week 28)
Title
Change From Baseline in Asthma Control Questionnaire (ACQ) at Weeks 4, 8, 12 and 16
Description
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.
Time Frame
Baseline (Day 1), Weeks 4, 8, 12 and 16
Title
Participants With Treatment-Emergent Adverse Events
Description
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.
Time Frame
Day 1 to Week 28
Title
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values
Description
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 baseline
Time Frame
Week 4 to Week 16
Title
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values
Description
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° Celsius
Time Frame
Week 4 to Week 28
Title
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Electrocardiogram (ECG) Abnormalities
Description
Counts represent the number of participants with potentially clinically significant ECG abnormalities as assessed by the investigator.
Time Frame
Week 16 or endpoint
Title
Participants With a Positive Anti-Reslizumab Antibody Status During Study
Description
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.
Time Frame
Screening (Week -3), Weeks 8 and 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Respiratory Clinical Research, M.D.
Organizational Affiliation
Sponsor's Medical Expert
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site 861
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Investigational Site 842
City
Homewood
State/Province
Alabama
Country
United States
Facility Name
Investigational Site 887
City
Jasper
State/Province
Alabama
Country
United States
Facility Name
Investigational Site 809
City
Tucson
State/Province
Arizona
Country
United States
Facility Name
Investigational Site 892
City
Tucson
State/Province
Arizona
Country
United States
Facility Name
Investigational Site 846
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
Investigational Site 828
City
Anaheim
State/Province
California
Country
United States
Facility Name
Investigational Site 900
City
Fresno
State/Province
California
Country
United States
Facility Name
Investigational Site 862
City
Huntington Beach
State/Province
California
Country
United States
Facility Name
Investigational Site 852
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Investigational Site 909
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Investigational Site 864
City
Newport Beach
State/Province
California
Country
United States
Facility Name
Investigational Site 812
City
Rancho Mirage
State/Province
California
Country
United States
Facility Name
Investigational Site 808
City
Riverside
State/Province
California
Country
United States
Facility Name
Investigational Site 804
City
Sacramento
State/Province
California
Country
United States
Facility Name
Investigational Site 837
City
Centennial
State/Province
Colorado
Country
United States
Facility Name
Investigational Site 851
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Investigational Site 832
City
Wheat Ridge
State/Province
Colorado
Country
United States
Facility Name
Investigational Site 855
City
Jacksonville
State/Province
Florida
Country
United States
Facility Name
Investigational Site 865
City
Miami
State/Province
Florida
Country
United States
Facility Name
Investigational Site 881
City
Miami
State/Province
Florida
Country
United States
Facility Name
Investigational Site 805
City
Albany
State/Province
Georgia
Country
United States
Facility Name
Investigational Site 870
City
Stockbridge
State/Province
Georgia
Country
United States
Facility Name
Investigational Site 816
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Investigational Site 824
City
Shiloh
State/Province
Illinois
Country
United States
Facility Name
Investigational Site 883
City
Evansville
State/Province
Indiana
Country
United States
Facility Name
Investigational Site 878
City
Fort Wayne
State/Province
Indiana
Country
United States
Facility Name
Investigational Site 820
City
Lenexa
State/Province
Kansas
Country
United States
Facility Name
Investigational Site 873
City
Owensboro
State/Province
Kentucky
Country
United States
Facility Name
Investigational Site 801
City
Lafayette
State/Province
Louisiana
Country
United States
Facility Name
Investigational Site 877
City
Mandeville
State/Province
Louisiana
Country
United States
Facility Name
Investigational Site 875
City
White Marsh
State/Province
Maryland
Country
United States
Facility Name
Investigational Site 871
City
Fall River
State/Province
Massachusetts
Country
United States
Facility Name
Investigational Site 834
City
North Dartmouth
State/Province
Massachusetts
Country
United States
Facility Name
Investigational Site 889
City
Troy
State/Province
Michigan
Country
United States
Facility Name
Investigational Site 838
City
Rolla
State/Province
Missouri
Country
United States
Facility Name
Investigational Site 818
City
St. Louis
State/Province
Missouri
Country
United States
Facility Name
Investigational Site 841
City
St. Louis
State/Province
Missouri
Country
United States
Facility Name
Investigational Site 857
City
Albuquerque
State/Province
New Mexico
Country
United States
Facility Name
Investigational Site 819
City
Newburgh
State/Province
New York
Country
United States
Facility Name
Investigational Site 844
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Investigational Site 845
City
Middleburg Heights
State/Province
Ohio
Country
United States
Facility Name
Investigational Site 810
City
Tulsa
State/Province
Oklahoma
Country
United States
Facility Name
Investigational Site 859
City
Ashland
State/Province
Oregon
Country
United States
Facility Name
Investigational Site 859
City
Portland
State/Province
Oregon
Country
United States
Facility Name
Investigational Site 854
City
Jenkintown
State/Province
Pennsylvania
Country
United States
Facility Name
Investigational Site 843
City
Providence
State/Province
Rhode Island
Country
United States
Facility Name
Investigational Site 802
City
Florence
State/Province
South Carolina
Country
United States
Facility Name
Investigational Site 814
City
Orangeburg
State/Province
South Carolina
Country
United States
Facility Name
Investigational Site 821
City
Spartanburg
State/Province
South Carolina
Country
United States
Facility Name
Investigational Site 829
City
Spartanburg
State/Province
South Carolina
Country
United States
Facility Name
Investigational Site 850
City
Knoxville
State/Province
Tennessee
Country
United States
Facility Name
Investigational Site 803
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Investigational Site 880
City
Dallas
State/Province
Texas
Country
United States
Facility Name
Investigational Site 858
City
Dickinson
State/Province
Texas
Country
United States
Facility Name
Investigational Site 869
City
Live Oak
State/Province
Texas
Country
United States
Facility Name
Investigational Site 879
City
Plano
State/Province
Texas
Country
United States
Facility Name
Investigational Site 847
City
Salt Lake City
State/Province
Utah
Country
United States
Facility Name
Investigational Site 876
City
West Jordan
State/Province
Utah
Country
United States
Facility Name
Investigational Site 840
City
Fairfax
State/Province
Virginia
Country
United States
Facility Name
Investigational Site 836
City
Richmond
State/Province
Virginia
Country
United States
Facility Name
Investigational Site 867
City
Seattle
State/Province
Washington
Country
United States
Facility Name
Investigational Site 833
City
Spokane
State/Province
Washington
Country
United States
Facility Name
Investigational Site 904
City
Vancouver
State/Province
Washington
Country
United States
Facility Name
Investigational Site 806
City
Greenfield
State/Province
Wisconsin
Country
United States
Facility Name
Investigational Site 823
City
LaCrosse
State/Province
Wisconsin
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27018175
Citation
Corren J, Weinstein S, Janka L, Zangrilli J, Garin M. Phase 3 Study of Reslizumab in Patients With Poorly Controlled Asthma: Effects Across a Broad Range of Eosinophil Counts. Chest. 2016 Oct;150(4):799-810. doi: 10.1016/j.chest.2016.03.018. Epub 2016 Mar 25.
Results Reference
derived
Learn more about this trial
Study to Evaluate the Efficacy and Safety of Reslizumab Treatment in Patients With Moderate to Severe Asthma
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