Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety, and Tolerability of SAR231893/REGN668 Administered Subcutaneously Once Weekly for 12 Weeks in Patients With Persistent Moderate to Severe Eosinophilic Asthma Who Are Partially Controlled/Uncontrolled by Inhaled Corticosteroid Plus Long-acting beta2 Agonist Therapy
Overview
- Phase
- Phase 2
- Intervention
- Placebo (for Dupilumab)
- Conditions
- Asthma
- Sponsor
- Sanofi
- Enrollment
- 104
- Locations
- 50
- Primary Endpoint
- Percentage of Participants With Asthma Exacerbation
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
Primary Objective:
To investigate the effects of Dupilumab (SAR231893/REGN668) administered subcutaneously (SC) once weekly (qw) for 12 weeks as compared to placebo on reducing the incidence of asthma exacerbation in participants with persistent moderate to severe eosinophilic asthma.
Secondary Objectives:
- To assess the safety and tolerability of Dupilumab administered SC qw for 12 weeks in participants with persistent moderate to severe eosinophilic asthma.
- To assess Dupilumab serum concentrations following qw SC dosing for 12 weeks in participants with persistent moderate to severe eosinophilic asthma.
Detailed Description
The total duration of the study period per participant was 20-22 weeks broken down as follows: * Screening period: up to 14 days, * Treatment period: 12 weeks, * Follow-up period: 6-8 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Placebo (for Dupilumab)
Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of inhaled corticosteroids/long-acting beta2-adrenergic agonist (ICS/LABA) (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Intervention: Placebo (for Dupilumab)
Placebo (for Dupilumab)
Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of inhaled corticosteroids/long-acting beta2-adrenergic agonist (ICS/LABA) (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Intervention: Fluticasone/Salmeterol combination therapy
Placebo (for Dupilumab)
Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of inhaled corticosteroids/long-acting beta2-adrenergic agonist (ICS/LABA) (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Intervention: Fluticasone monotherapy
Placebo (for Dupilumab)
Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of inhaled corticosteroids/long-acting beta2-adrenergic agonist (ICS/LABA) (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Intervention: Albuterol
Placebo (for Dupilumab)
Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of inhaled corticosteroids/long-acting beta2-adrenergic agonist (ICS/LABA) (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Intervention: Levalbuterol
Dupilumab 300 mg qw
Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Intervention: Dupilumab
Dupilumab 300 mg qw
Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Intervention: Fluticasone/Salmeterol combination therapy
Dupilumab 300 mg qw
Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Intervention: Fluticasone monotherapy
Dupilumab 300 mg qw
Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Intervention: Albuterol
Dupilumab 300 mg qw
Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Intervention: Levalbuterol
Outcomes
Primary Outcomes
Percentage of Participants With Asthma Exacerbation
Time Frame: Baseline up to Week 12
An asthma exacerbation was defined as the occurrence of any of the following: ≥30% reduction from baseline in morning PEF on 2 consecutive days; or ≥6 additional reliever puffs of albuterol or levalbuterol in a 24-hour period (compared to baseline) on 2 consecutive days; or deterioration of asthma, as determined by the investigator, requiring systemic steroid treatment, or an increase in inhaled corticosteroid (ICS) of ≥4 times the last dose received prior to discontinuation from the study, or hospitalization. The occurrence of asthma exacerbations by individual criteria are reported.
Secondary Outcomes
- Change From Baseline in Number of Nocturnal Awakenings Per Day to Week 12(Baseline, Week 12)
- Change From Baseline in Number of Inhalations Per Day of Albuterol or Levalbuterol to Week 12(Baseline, Week 12)
- Change From Baseline in Peak Expiratory Flow (PEF) to Week 12(Baseline, Week 12)
- Change From Baseline in Morning Asthma Symptom Scores to Week 12(Baseline, Week 12)
- Percentage of Participants With Composite Asthma Events(Baseline up to Week 12)
- Change From Baseline in 22-item Sinonasal Outcome Test (SNOT-22) Score to Week 12(Baseline, Week 12)
- Change From Baseline in Evening Asthma Symptom Scores to Week 12(Baseline, Week 12)
- Time to First Asthma Exacerbation: Kaplan-Meier Estimates at Week 4, Week 8 and Week 12(Baseline up to Week 12)
- Change From Baseline in Forced Expiratory Flow in One Second (FEV1) to Week 12(Baseline, Week 12)
- Change From Baseline in Asthma Control Questionnaire (5-question Version [ACQ-5]) to Week 12(Baseline, Week 12)