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Efficacy and Safety Study of Reslizumab to Treat Poorly Controlled Asthma

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ClinicalTrials.gov Identifier: NCT00587288
Recruitment Status : Completed
First Posted : January 7, 2008
Results First Posted : April 26, 2016
Last Update Posted : August 17, 2016
Sponsor:
Collaborator:
Cephalon
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Ception Therapeutics )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Asthma
Interventions Biological: Reslizumab
Other: Saline
Enrollment 106
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Reslizumab 3 mg/kg Placebo
Hide Arm/Group Description reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Period Title: Overall Study
Started 53 53
Completed 50 44
Not Completed 3 9
Reason Not Completed
Adverse Event             0             1
Lack of Efficacy             2             8
Protocol Violation             1             0
Arm/Group Title Reslizumab 3 mg/kg Placebo Total
Hide Arm/Group Description reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles Total of all reporting groups
Overall Number of Baseline Participants 53 53 106
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 53 participants 53 participants 106 participants
44.9  (13.94) 45.8  (11.74) 45.4  (12.83)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 53 participants 53 participants 106 participants
18 to < 45 years 28 20 48
45 to < 65 years 19 32 51
>/= 65 years 6 1 7
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 53 participants 106 participants
Female
34
  64.2%
29
  54.7%
63
  59.4%
Male
19
  35.8%
24
  45.3%
43
  40.6%
1.Primary Outcome
Title Mean Change From Baseline to End of Therapy in Asthma Control Questionnaire (ACQ) Score
Hide Description The ACQ is a 7 question instrument. Each question has 7 possible answers of 0, 1, 2, 3, 4, 5, and 6. Each increasing value is an indication of poorer asthma control. At protocol specified visits, the participant answered questions 1 to 6, circling the response that best described how that participant was during the past week, on the basis of a daily diary for the week before the visit. At the actual visit, study center personnel reviewed the questions and responses with the participant and determined the response and score for question 7. The overall ACQ score was presented as the mean of these 7 individual scores and was a number between 0 and 6, but not necessarily an integer.
Time Frame Baseline through End of Therapy (up to 15 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) Analysis Set: all participants who received any amount of randomly assigned study drug.
Arm/Group Title Reslizumab 3 mg/kg Placebo
Hide Arm/Group Description:
reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Overall Number of Participants Analyzed 53 53
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.7  (1.02) -0.3  (1.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reslizumab 3 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0541
Comments The p-value for the treatment comparison is based on the ANCOVA with adjustment for stratification factor and for variable at baseline.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.76 to 0.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.194
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of ACQ Responders at End of Therapy
Hide Description Responders were defined as participants achieving at least a 0.5 reduction from baseline to End of Therapy in ACQ score. The ACQ is a 7 question instrument. Each question has 7 possible answers of 0, 1, 2, 3, 4, 5, and 6. Each increasing value is an indication of poorer asthma control. At protocol specified visits, the participant answered questions 1 to 6, circling the response that best described how that participant was during the past week, on the basis of a daily diary for the week before the visit. At the actual visit, study center personnel reviewed the questions and responses with the participant and determined the response and score for question 7. The overall ACQ score was presented as the mean of these 7 individual scores and was a number between 0 and 6, but not necessarily an integer.
Time Frame Baseline, End of Therapy (up to 15 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received any amount of randomly assigned study drug.
Arm/Group Title Reslizumab 3 mg/kg Placebo
Hide Arm/Group Description:
reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Overall Number of Participants Analyzed 53 53
Measure Type: Number
Unit of Measure: percentage of participants
Responder = yes 55 36
Responder = no 45 64
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reslizumab 3 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0848
Comments The p-value for the treatment comparison was based on logistic regression with adjustment for stratification factor.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.01
Confidence Interval (2-Sided) 95%
0.91 to 4.46
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to End of Therapy in Forced Expiratory Volume in the First Second (FEV1)
Hide Description The change in FEV1 from baseline to End of Therapy was determined. FEV1 was measured during pulmonary function tests using standard spirometry measurements.
Time Frame Baseline, End of Therapy (up to 15 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.
Arm/Group Title Reslizumab 3 mg/kg Placebo
Hide Arm/Group Description:
reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Overall Number of Participants Analyzed 52 52
Mean (Standard Deviation)
Unit of Measure: L
0.18  (0.372) -0.08  (0.413)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reslizumab 3 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0023
Comments The p-value for the treatment comparison was based on the ANCOVA with adjustment for stratification factor and for variable at baseline.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 0.240
Confidence Interval (2-Sided) 95%
0.088 to 0.392
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.077
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to End of Therapy in Percent Predicted FEV1
Hide Description The change in percent predicted FEV1 from baseline to End of Therapy was calculated from the FEV1 measured during pulmonary function tests using standard spirometry measurements. Each participant’s percent predicted FEV1 was calculated by adjusting the FEV1 for age, sex, height and race. The percent predicted FEV1 was then calculated by comparing the predicted FEV1 to the observed FEV1 using the Crapo formula (Crapo et al 1981a, Crapo and Morris 1981b, Crapo et al 1982).
Time Frame Baseline, End of Therapy (up to 15 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.
Arm/Group Title Reslizumab 3 mg/kg Placebo
Hide Arm/Group Description:
reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Overall Number of Participants Analyzed 52 52
Mean (Standard Deviation)
Unit of Measure: percent predicted FEV1
6.2  (11.76) -2.4  (12.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reslizumab 3 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments The p-value for the treatment comparison was based on the ANCOVA with adjustment for stratification factor and for variable at baseline.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 7.98
Confidence Interval (2-Sided) 95%
3.30 to 12.65
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.36
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline to End of Therapy in Induced Sputum Eosinophil Levels
Hide Description [Not Specified]
Time Frame End of Screening or Baseline, End of Therapy (up to 15 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.
Arm/Group Title Reslizumab 3 mg/kg Placebo
Hide Arm/Group Description:
reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Overall Number of Participants Analyzed 38 36
Mean (Standard Deviation)
Unit of Measure: percent change in eosinophil levels
-82.0  (66.88) 45.9  (265.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reslizumab 3 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0068
Comments The p-value for the treatment comparison was based on the ANCOVA with adjustment for stratification factor and for variable at baseline. The difference between reslizumab 3.0 mg/kg and placebo groups was from comparison of the least square means.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -125.29
Confidence Interval (2-Sided) 95%
-214.81 to -35.77
Parameter Dispersion
Type: Standard Error of the mean
Value: 44.885
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Clinical Asthma Exacerbations (CAEs)
Hide Description A CAE was defined as a 20% or more decrease in forced expiratory volume in 1 second (FEV1, absolute value) from the baseline value, a requirement for emergency treatment of asthma, hospital admission for asthma, or treatment with 3 or more days of oral corticosteroids for asthma worsening.
Time Frame up to 15 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received any amount of randomly assigned study drug.
Arm/Group Title Reslizumab 3 mg/kg Placebo
Hide Arm/Group Description:
reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Overall Number of Participants Analyzed 53 53
Measure Type: Number
Unit of Measure: percentage of participants
8 19
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reslizumab 3 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0833
Comments The p-value for the treatment comparison was based on logistic regression with adjustment for stratification factor.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.10 to 1.15
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reslizumab 3 mg/kg, Placebo
Comments Kaplan-Meier estimate of time to first CAE. (First quartile, median and third quartile “survival” times with 95% confidence intervals (ie, time to first CAE) could not be estimated since the proportion of patients experiencing CAE was too low. Therefore, the only number presented in regard to the Kaplan-Meier analysis is the p-value of the log-rank test, below. )
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0809
Comments [Not Specified]
Method Log Rank
Comments The p value for the treatment comparison was based on log rank test adjusting for stratification factor (ie, ACQ score ≤2 and >2).
7.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation
Hide Description Participants may have been included in more than 1 category. AEs summarized were those that began or worsened after dispensation of the study drug and before 30 days after the last dose of study drug. If the severity of an AE was missing, the AE was reported as “severe.” If drug relationship of an AE was missing, the AE was reported as “probably related.” WFT=withdrawn from treatment.
Time Frame From start of study drug through 15 weeks + 30 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.
Arm/Group Title Reslizumab 3 mg/kg Placebo
Hide Arm/Group Description:
Reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Overall Number of Participants Analyzed 53 53
Measure Type: Number
Unit of Measure: participants
Any AE 38 42
Severe or life-threatening AE 3 1
Treatment-related AE 12 8
Deaths 0 0
Serious AEs other than death 2 1
Treatment-related serious AEs 0 0
WFT or study due to AEs 1 1
WFT or study due to treatment-related AEs 0 1
Time Frame From start of study drug through 15 weeks + 30 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Reslizumab 3 mg/kg Placebo
Hide Arm/Group Description reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
All-Cause Mortality
Reslizumab 3 mg/kg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Reslizumab 3 mg/kg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/53 (3.77%)      1/53 (1.89%)    
Infections and infestations     
PNEUMONIA  1  1/53 (1.89%)  1 0/53 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
ASTHMA  1  1/53 (1.89%)  1 0/53 (0.00%)  0
Vascular disorders     
HYPERTENSION  1  0/53 (0.00%)  0 1/53 (1.89%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Reslizumab 3 mg/kg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/53 (32.08%)      17/53 (32.08%)    
General disorders     
FATIGUE  1  4/53 (7.55%)  4 2/53 (3.77%)  2
Infections and infestations     
BRONCHITIS  1  2/53 (3.77%)  2 3/53 (5.66%)  3
NASOPHARYNGITIS  1  11/53 (20.75%)  14 5/53 (9.43%)  6
UPPER RESPIRATORY TRACT INFECTION  1  2/53 (3.77%)  3 5/53 (9.43%)  5
Nervous system disorders     
HEADACHE  1  2/53 (3.77%)  3 5/53 (9.43%)  5
Respiratory, thoracic and mediastinal disorders     
PHARYNGOLARYNGEAL PAIN  1  3/53 (5.66%)  3 0/53 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.1
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.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 215-591-3000
Responsible Party: Teva Pharmaceutical Industries ( Ception Therapeutics )
ClinicalTrials.gov Identifier: NCT00587288     History of Changes
Other Study ID Numbers: Res-5-0010
First Submitted: January 4, 2008
First Posted: January 7, 2008
Results First Submitted: March 23, 2016
Results First Posted: April 26, 2016
Last Update Posted: August 17, 2016