Asthma
Conditions
Keywords
Cinquil™, Reslizumab
Brief summary
The purpose of this study is to determine the effectiveness and safety of reslizumab in the treatment of subjects with poorly controlled asthma.
Detailed description
Objectives: Primary: To demonstrate the ability of reslizumab to improve asthma control in subjects with active asthma and eosinophilic airway inflammation. Secondary: * To study the ability of reslizumab to reduce induced sputum eosinophil (EOS) counts in subjects with asthma. * To study the ability of reslizumab to reduce the number of eosinophilic clinical asthma exacerbations (CAE) in subjects with asthma. A CAE is defined as a ≥ 20% decrease in forced expiratory volume in 1 second (FEV1; absolute value) from the baseline value or a requirement for emergency treatment of asthma, hospital admission for asthma or treatment with three or more days of oral corticosteroids (OCS) for asthma worsening. * To assess the safety and tolerability of reslizumab in subjects with asthma.
Interventions
BIOLOGICALReslizumab
OTHERSaline
Sponsors
Cephalon
Ception Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* written informed consent * male or female subjects aged ≥ 18 to 75 years at time of screening * female if she is of non-childbearing potential, or of childbearing potential and willing to use specific barrier methods specified in protocol * confirmation of asthma * symptoms consistent with a diagnosis of asthma that is poorly controlled with an inhaled corticosteroid as determined by an Asthma Control Questionnaire (ACQ) score ≥ 1.5 * requirement for treatment with high dose daily fluticasone and at least one other agent for the treatment of asthma not specifically excluded in the protocol * requirement for \>/= 3% eosinophils in induced sputum at Screening
Exclusion criteria
* a clinically important event that would interfere with study schedule or procedure or compromise subject safety * a diagnosis of hypereosinophilic syndrome * an underlying lung disorder * a current smoker * use of systemic immunosuppressive agents within 6 months of study * current use of systemic corticosteroids * received attenuated live attenuated vaccines within three months prior to study entry * expected to be poorly compliant with study drug, procedures, visits * aggravating factors that are inadequately controlled * participation in any investigational drug or device study within 30 days prior to study entry * participation in biologics study within 3 months prior to study entry * receipt of anti-human interleukin-5 (hIL-5) antibody within 6 months of study entry * female subjects who are pregnant or nursing * concurrent infection or disease that may preclude assessment of eosinophilic esophagitis * concurrent immunodeficiency (human immunodeficiency \[HIV\], or acquired immunodeficiency syndrome \[AIDS\] or congenital immunodeficiency). * current suspected drug and/or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to End of Therapy in Asthma Control Questionnaire (ACQ) Score | Baseline through End of Therapy (up to 15 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Therapy in Forced Expiratory Volume in the First Second (FEV1) | Baseline, End of Therapy (up to 15 weeks) | The change in FEV1 from baseline to End of Therapy was determined. FEV1 was measured during pulmonary function tests using standard spirometry measurements. |
| Change From Baseline to End of Therapy in Percent Predicted FEV1 | Baseline, End of Therapy (up to 15 weeks) | 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). |
| Percentage of ACQ Responders at End of Therapy | Baseline, End of Therapy (up to 15 weeks) | 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. |
| Percentage of Participants With Clinical Asthma Exacerbations (CAEs) | up to 15 weeks | 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. |
| Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | From start of study drug through 15 weeks + 30 days | 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. |
| Mean Change From Baseline to End of Therapy in Induced Sputum Eosinophil Levels | End of Screening or Baseline, End of Therapy (up to 15 weeks) | — |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Reslizumab 3 mg/kg reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles | 53 |
| Placebo saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles | 53 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lack of Efficacy | 2 | 8 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Reslizumab 3 mg/kg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 44.9 years STANDARD_DEVIATION 13.94 | 45.8 years STANDARD_DEVIATION 11.74 | 45.4 years STANDARD_DEVIATION 12.83 |
| Age, Customized 18 to < 45 years | 28 participants | 20 participants | 48 participants |
| Age, Customized 45 to < 65 years | 19 participants | 32 participants | 51 participants |
| Age, Customized >/= 65 years | 6 participants | 1 participants | 7 participants |
| Sex: Female, Male Female | 34 Participants | 29 Participants | 63 Participants |
| Sex: Female, Male Male | 19 Participants | 24 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 53 | 17 / 53 |
| serious Total, serious adverse events | 2 / 53 | 1 / 53 |
Outcome results
Primary
Mean Change From Baseline to End of Therapy in Asthma Control Questionnaire (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 through End of Therapy (up to 15 weeks)
Population: Intent-to-treat (ITT) Analysis Set: all participants who received any amount of randomly assigned study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reslizumab 3 mg/kg | Mean Change From Baseline to End of Therapy in Asthma Control Questionnaire (ACQ) Score | -0.7 units on a scale | Standard Deviation 1.02 |
| Placebo | Mean Change From Baseline to End of Therapy in Asthma Control Questionnaire (ACQ) Score | -0.3 units on a scale | Standard Deviation 1.01 |
p-value: 0.054195% CI: [-0.76, 0.01]ANCOVA
Secondary
Change From Baseline to End of Therapy in Forced Expiratory Volume in the First Second (FEV1)
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)
Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reslizumab 3 mg/kg | Change From Baseline to End of Therapy in Forced Expiratory Volume in the First Second (FEV1) | 0.18 L | Standard Deviation 0.372 |
| Placebo | Change From Baseline to End of Therapy in Forced Expiratory Volume in the First Second (FEV1) | -0.08 L | Standard Deviation 0.413 |
p-value: 0.002395% CI: [0.088, 0.392]ANCOVA
Secondary
Change From Baseline to End of Therapy in Percent Predicted FEV1
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)
Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reslizumab 3 mg/kg | Change From Baseline to End of Therapy in Percent Predicted FEV1 | 6.2 percent predicted FEV1 | Standard Deviation 11.76 |
| Placebo | Change From Baseline to End of Therapy in Percent Predicted FEV1 | -2.4 percent predicted FEV1 | Standard Deviation 12.93 |
p-value: 0.00195% CI: [3.3, 12.65]ANCOVA
Secondary
Mean Change From Baseline to End of Therapy in Induced Sputum Eosinophil Levels
Time frame: End of Screening or Baseline, End of Therapy (up to 15 weeks)
Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reslizumab 3 mg/kg | Mean Change From Baseline to End of Therapy in Induced Sputum Eosinophil Levels | -82.0 percent change in eosinophil levels | Standard Deviation 66.88 |
| Placebo | Mean Change From Baseline to End of Therapy in Induced Sputum Eosinophil Levels | 45.9 percent change in eosinophil levels | Standard Deviation 265.79 |
p-value: 0.006895% CI: [-214.81, -35.77]ANCOVA
Secondary
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation
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
Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reslizumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Any AE | 38 participants |
| Reslizumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Severe or life-threatening AE | 3 participants |
| Reslizumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Treatment-related AE | 12 participants |
| Reslizumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Deaths | 0 participants |
| Reslizumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Serious AEs other than death | 2 participants |
| Reslizumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Treatment-related serious AEs | 0 participants |
| Reslizumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | WFT or study due to AEs | 1 participants |
| Reslizumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | WFT or study due to treatment-related AEs | 0 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | WFT or study due to treatment-related AEs | 1 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Any AE | 42 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Serious AEs other than death | 1 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Severe or life-threatening AE | 1 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | WFT or study due to AEs | 1 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Treatment-related AE | 8 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Treatment-related serious AEs | 0 participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Deaths | 0 participants |
Secondary
Percentage of ACQ Responders at End of Therapy
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)
Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reslizumab 3 mg/kg | Percentage of ACQ Responders at End of Therapy | Responder = yes | 55 percentage of participants |
| Reslizumab 3 mg/kg | Percentage of ACQ Responders at End of Therapy | Responder = no | 45 percentage of participants |
| Placebo | Percentage of ACQ Responders at End of Therapy | Responder = yes | 36 percentage of participants |
| Placebo | Percentage of ACQ Responders at End of Therapy | Responder = no | 64 percentage of participants |
p-value: 0.084895% CI: [0.91, 4.46]Regression, Logistic
Secondary
Percentage of Participants With Clinical Asthma Exacerbations (CAEs)
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
Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reslizumab 3 mg/kg | Percentage of Participants With Clinical Asthma Exacerbations (CAEs) | 8 percentage of participants |
| Placebo | Percentage of Participants With Clinical Asthma Exacerbations (CAEs) | 19 percentage of participants |
p-value: 0.083395% CI: [0.1, 1.15]Regression, Logistic
Comparison: 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. )p-value: 0.0809Log Rank