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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier:
NCT01287039
First received: January 28, 2011
Last updated: May 26, 2016
Last verified: May 2016
Results First Received: March 23, 2016  
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
Condition: Eosinophilic Asthma
Interventions: Drug: Reslizumab
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 1486 patients were screened at 121 centers. Of the 1486 patients screened, 489 patients with asthma and blood eosinophils ≥400/ μL at 102 centers in 17 countries were randomly assigned to double-blind treatment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
997 of 1486 screened patients were not randomized: 888 were excluded on the basis of not meeting inclusion criteria, 23 withdrew consent, 17 had an adverse event during the screening period, 12 met an exclusion criterion, 7 were lost to follow-up and 50 were excluded for other reasons. One placebo patient was randomized but not treated.

Reporting Groups
  Description
Placebo Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Reslizumab 3.0 mg/kg Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.

Participant Flow:   Overall Study
    Placebo     Reslizumab 3.0 mg/kg  
STARTED     244     245  
COMPLETED     215     218  
NOT COMPLETED     29     27  
Noncompliance with study procedures                 0                 1  
Change of location/residence                 0                 3  
Elective surgery                 0                 1  
Protocol Violation                 2                 3  
Excluded medication taken                 1                 0  
Noncompliance with study medication                 0                 1  
Problem with travel                 0                 1  
Death                 1                 0  
Change of residence                 1                 0  
Adverse Event                 7                 4  
Withdrawal by Subject                 14                 11  
Lost to Follow-up                 3                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized set

Reporting Groups
  Description
Placebo Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Reslizumab 3.0 mg/kg Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Total Total of all reporting groups

Baseline Measures
    Placebo     Reslizumab 3.0 mg/kg     Total  
Number of Participants  
[units: participants]
  244     245     489  
Age  
[units: years]
Mean (Standard Deviation)
  46.7  (14.83)     46.6  (13.82)     46.6  (14.32)  
Gender  
[units: participants]
     
Female     161     142     303  
Male     83     103     186  
Race/Ethnicity, Customized  
[units: participants]
     
White     182     173     355  
Black     20     14     34  
Asian     33     50     83  
American Indian or Alaskan Native     0     0     0  
Pacific Islander     0     1     1  
Other     9     7     16  
Race/Ethnicity, Customized  
[units: participants]
     
Non-Hispanic and non-Latino     223     216     439  
Hispanic or Latino     21     28     49  
Unknown     0     1     1  
Weight  
[units: kg]
Mean (Standard Deviation)
  76.5  (18.71)     75.6  (19.05)     76.0  (18.87)  
Height  
[units: cm]
Mean (Standard Deviation)
  165.0  (9.74)     164.9  (10.42)     164.9  (10.07)  
Body Mass Index  
[units: kg/m^2]
Mean (Standard Deviation)
  28.0  (6.16)     27.7  (6.26)     27.9  (6.20)  
Oral Glucocorticosteroid (OCS) Use at Baseline [1]
[units: participants]
     
OCS - Yes     46     46     92  
OCS - No     198     199     397  
Asthma Exacerbations In Previous 12 Months  
[units: exacerbations]
Mean (Standard Deviation)
  2.1  (2.31)     1.9  (1.63)     2.0  (2.00)  
Forced Expiratory Volume in 1 Second  
[units: liters]
Mean (Standard Deviation)
  1.928  (0.7908)     1.894  (0.7258)     1.911  (0.7583)  
Asthma Control Questionnaire (ACQ) Overall Score [2]
[units: units on a scale]
Mean (Standard Deviation)
  2.763  (0.8782)     2.657  (0.8541)     2.710  (0.867)  
Asthma Quality of Life Questionnaire (AQLQ) [3]
[units: units on a scale]
Mean (Standard Deviation)
  4.159  (1.0883)     4.303  (1.1208)     4.231  (1.1059)  
Asthma Symptom Utility Index (ASUI) [4]
[units: units on a scale]
Mean (Standard Deviation)
  0.613  (0.2029)     0.633  (0.1938)     0.623  (0.1984)  
Number of Short-Acting Beta-Agonist Puffs (SABA) Daily [5]
[units: puffs/day]
Mean (Standard Deviation)
  2.7  (3.18)     2.4  (2.82)     2.6  (3.01)  
[1] Oral glucocorticosteroid (OCS) use at baseline was a stratification factor. Values input by the investigator into the interactive response technology (IRT) were used during randomization. However, 6 patients in the placebo group and 22 patients in the reslizumab group were misclassified in IRT as having used oral glucocorticosteroids at baseline according to the case report form.
[2] The ACQ is a 7-item instrument that measures asthma control (Juniper et al 1999). Six questions are self-assessments; the seventh item, completed by a member of the study staff, is the result of the patient’s FEV1 measurement. Each item has 7 possible answers on a scale of 0 to 6, and the overall score is the mean of all responses. A higher score is an indication of poorer asthma control.
[3] The AQLQ is a 32-item instrument administered as a self-assessment (Juniper et al 1992). The questionnaire is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (1=severe impairment, 7=no impairment). The overall AQLQ score is the mean of all 32 responses.
[4] The ASUI is an 11-item instrument designed to assess the frequency and severity of asthma symptoms and side effects, weighted by patient preferences (Revicki et al 1998). ASUI is a utility score that ranges from 0 to 1, with higher values indicating better asthma control.
[5] Based on patient-reported total number of SABA puffs over the past 3 days.



  Outcome Measures
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1.  Primary:   Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment   [ Time Frame: Day 1 to Week 52 ]

2.  Primary:   Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs)   [ Time Frame: Day 1 to Week 52 ]

3.  Secondary:   Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures   [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12 and 16 ]

4.  Secondary:   Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16   [ Time Frame: Day 1 (baseline, pre-dose), Week 16 ]

5.  Secondary:   Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures   [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 ]

6.  Secondary:   Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE)   [ Time Frame: Day 1 to Day 478 (longest treatment time plus 2 weeks) ]

7.  Secondary:   Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures   [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 ]

8.  Secondary:   Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures   [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 ]

9.  Secondary:   Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures   [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 or early withdrawal ]

10.  Secondary:   Participants With Treatment-Emergent Adverse Events   [ Time Frame: Day 1 (post-dose) to Week 65. The last postbaseline value for approximately 20 patients in each ]

11.  Secondary:   Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values   [ Time Frame: Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each ]

12.  Secondary:   Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values   [ Time Frame: Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each ]

13.  Secondary:   Participants With a Positive Anti-Reslizumab Antibody Status During Study   [ Time Frame: Weeks 16, 32, 48 and 52 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc
phone: 215-591-3000
e-mail: ustevatrials@tevapharm.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT01287039     History of Changes
Other Study ID Numbers: C38072/3082
Study First Received: January 28, 2011
Results First Received: March 23, 2016
Last Updated: May 26, 2016
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