Efficacy and Safety Study of Reslizumab to Treat Poorly Controlled Asthma

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Efficacy and Safety Study of Reslizumab in the Treatment of Poorly Controlled Asthma in Subjects With Eosinophilic Airway Inflammation

Conditions
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Asthma

Intervention / Treatment
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* Biological: Reslizumab
* Other: Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reslizumab 3 mg/kg<br>Reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles | Biological: Reslizumab<br> <br> * Other names: CTx55700;|
| Placebo Comparator: Placebo<br>Saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles | Other: Saline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline through End of Therapy (up to 15 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, End of Therapy (up to 15 weeks) | 
| 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. | Baseline, End of Therapy (up to 15 weeks) | 
| 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). | Baseline, End of Therapy (up to 15 weeks) | 
| 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) | 
| 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. | up to 15 weeks | 
| 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. | From start of study drug through 15 weeks + 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cinquil™, Reslizumab