An Efficacy and Safety Study of Reslizumab Subcutaneous in Patients With Oral Corticosteroid Dependent Asthma and Elevated Blood Eosinophils

Study Overview
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Brief Summary
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The primary objective of the study is to determine the ability of reslizumab administered by subcutaneous injection to produce a corticosteroid-sparing effect in patients with oral corticosteroid (OCS)-dependent asthma and elevated blood eosinophils, without loss of asthma control.

Official Title
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A Phase 3, 24-Week Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Study of Reslizumab Subcutaneous Dosing (110 mg Every 4 Weeks) in Patients With Oral Corticosteroid Dependent Asthma and Elevated Blood Eosinophils

Conditions
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Asthma, Elevated Blood Eosinophils, Oral Corticosteroid Dependence

Intervention / Treatment
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* Drug: Reslizumab
* Drug: Placebo
* Drug: Non-Oral Corticosteroid (non-OCS) Asthma Medication
* Drug: Oral Corticosteroid (OCS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is male or female, 12 years of age and older, with a previous diagnosis of asthma. Written informed consent is obtained. The patient requires daily maintenance dose of prednisone or equivalent for asthma of between 5 and 40 mg during the 3 months prior to screening. The patient has a documented elevated blood eosinophils at screening or during the previous 12 months. The patient has required high dose ICS plus another asthma controller for at least 6 months prior to screening. The patient has FEV1 reversibility to inhaled SABA or historical reversibility within the previous 24 months. Other criteria may apply, please contact the investigator for more information. Exclusion Criteria: The patient has any clinically significant, uncontrolled medical condition that would interfere with the study schedule or procedures and interpretation of efficacy results or would compromise the patient's safety. The patient has another confounding underlying lung disorder. The patient has a known hypereosinophilic syndrome. The patient has a history of any malignancy within 5 years of the screening visit, except for treated and cured non-melanoma skin cancers. The patient is pregnant or intends to become pregnant during the study or is lactating. The patient required treatment for an asthma exacerbation within 4 weeks of screening. The patient is a current smoker or has a smoking history ≥10 pack-years. The patient is currently using any systemic immunosuppressive or immunomodulatory biologic except maintenance OCS for the treatment of asthma. The patient participated in a clinical study within 30 days or 5 half-lives of the investigational drug before screening, whichever is longer. The patient was previously exposed to benralizumab within 12 months of screening. The patient was previously exposed to reslizumab. The patient has a history of immunodeficiency disorder including human immunodeficiency virus. The patient has current suspected drug and/or alcohol abuse. The patient has had an active helminthic parasitic infection or was treated for one within 6 months of screening. The patient has a history of allergic reactions or hypersensitivity to any component of the study drug. Other criteria may apply, please contact the investigator for more information.

Ages Eligible for Study
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Minimum Age: 12 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 110 mg<br>Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses. | Drug: Reslizumab<br>* Reslizumab 110 mg was administered by qualified study personnel as subcutaneous injections in the upper arm(s) once every 4 weeks for a total of 6 doses. Drug was supplied in pre-filled syringes.<br>* Other names: CEP38072;Drug: Non-Oral Corticosteroid (non-OCS) Asthma Medication<br>* Participants continue using their non-OCS background asthma medications without change during the study's treatment period.<br>Drug: Oral Corticosteroid (OCS)<br>* After screening and prior to study start, the participant's OCS dose was adjusted to determine the minimal effective OCS requirement.<br>|
| Placebo Comparator: Placebo<br>Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses. | Drug: Placebo<br>* Placebo was administered by qualified study personnel as subcutaneous injections in the upper arm(s) once every 4 weeks for a total of 6 doses. Drug was supplied in pre-filled syringes.<br>Drug: Non-Oral Corticosteroid (non-OCS) Asthma Medication<br>* Participants continue using their non-OCS background asthma medications without change during the study's treatment period.<br>Drug: Oral Corticosteroid (OCS)<br>* After screening and prior to study start, the participant's OCS dose was adjusted to determine the minimal effective OCS requirement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | The primary endpoint was the 5-level categorized percent reduction in OCS dose during weeks 20 to 24 compared with the optimized dose at baseline. The primary analysis incorporated data from all randomized patients. Analysis of the primary and secondary variables related to categorical OCS dose reduction incorporated missing data as non-responders. No decrease indicates there was no decrease in OCS, loss of baseline asthma control during weeks 20 to 24, or discontinuation from study drug. | Baseline (Day 1), Weeks 20-24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a >=50% Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | Percentage of patients whose OCS dose at weeks 20-24 was reduced >=50% compared to baseline while maintaining asthma control. Patients listed as no did not achieve the 50% reduction in baseline OCS dose goal, or did achieve that goal but lost asthma control during weeks 20 to 24, or discontinued from study drug. | Baseline (Day 1), Weeks 20-24 | 
| Percentage of Participants Achieving an OCS Dose of <=5 mg at Weeks 20-24 While Maintaining Asthma Control | Percentage of participants whose OCS dose at weeks 20-24 was <=5 mg and they maintained asthma control. Patients listed as no had a week 20-24 OCS dose > 5 mg, or whose OCS dose was <=5 mg at weeks 20-24 but did not maintain asthma control, or they discontinued from study drug. | Weeks 20-24 | 
| Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 Using a Mixed Model for Repeated Measures | The baseline OCS dose is the prescribed optimized OCS dose following the OCS optimization period. Endpoint data are presented using an on-treatment approach. In this context, 'endpoint' was defined as the last observation obtained at a scheduled or qualified early termination visit during the treatment period. Weeks 20-24 data is included between the Week 20 dose and Week 24 for completed patients; last dose of study drug to 4 weeks after the last dose of study drug for patients who discontinued treatment early. Measurements collected outside of these defined timeframes are excluded from the analyses. The mixed model repeated measures (MMRM) included fixed effects for treatment, visit, treatment by visit interaction, age group, and OCS dose group, duration of OCS use and baseline value as covariates, and patient as a random effect. Unstructured covariance was assumed for the repeated measures. | Baseline (Day 1), Weeks 20-24 | 
| Percentage of Participants Achieving a >=5 mg Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | Percentage of participants whose OCS dose at weeks 20-24 was reduced by at least 5mg from baseline and maintained asthma control. Patients listed as no had a week 20-24 OCS dose that did not meet the threshold of a 5mg reduction, or whose OCS dose met the threshold but did not maintain asthma control, or discontinued from study drug. | Baseline (Day 1), Weeks 20-24 | 
| Annualized Rate of Clinical Asthma Exacerbations (CAEs) | The annual exacerbation rate is based on clinical asthma exacerbations reported by the investigator in the eCRF. | Day 1 through Week 24 | 
| Percentage of Participants Achieving an OCS Dose of 0 mg at Weeks 20-24 While Maintaining Asthma Control | Percentage of participants who discontinue use of OCS during weeks 20-24 while maintaining asthma control. Patients listed as no continued to use OCS during weeks 20-24, or who discontinued use of OCS during weeks 20-24 but lost control of their asthma, or discontinued from study drug. | Weeks 20-24 | 
| Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses | Treatment-emergent responses were defined as a positive sample post-baseline (negative baseline) OR a titer increase of >=4-fold relative to a positive baseline sample. Two types of antibody assay were performed, an immunogenicity status assay (ADA) and neutralizing assay (NAb). The ADA assay produces a positive or negative result. For samples with a positive result, a neutralizing assay was performed, which also produces a positive or negative result. | Weeks 4, 8, 12, 24 or early withdrawal. | 
| Participants With Adverse Events | An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product, regardless of whether it has a causal relationship with this treatment. In this study, asthma exacerbations (which are efficacy parameters) should not be recorded as adverse events unless assessed by the investigator as more severe than the patient's usual disease course. 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. Treatment-related adverse events or adverse events related to OCS use included events with missing relationship to study drug or OCS use, respectively. | Day 1 up to Week 24 (end of treatment visit); Data were included between Day 1 and Week 24 for completed patients, and Day 1 and 4 weeks after the last dose of study drug for patients who discontinued treatment early. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Elevated Blood Eosinophils, Oral corticosteroid dependence, Reslizumab