A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate Dupilumab in Patients With Moderate to Severe Uncontrolled Asthma
Overview
- Phase
- Phase 2
- Intervention
- Dupilumab
- Conditions
- Asthma
- Sponsor
- Sanofi
- Enrollment
- 776
- Locations
- 201
- Primary Endpoint
- Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
Primary Objective:
To evaluate the efficacy of different doses and regimens of dupilumab in participants with moderate to severe uncontrolled asthma.
Secondary Objective:
To evaluate different doses and regimens of dupilumab in participants with moderate to severe uncontrolled asthma, with regard to:
- Safety and tolerability
- Dupilumab systemic exposure and anti-drug antibodies
Detailed Description
Total duration per participant of approximately 43 weeks including a screening period (14-21 days), a randomized treatment period (24 weeks), and a post-treatment period (16 weeks).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Dupilumab 300 mg q2w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1), followed by a single 300 mg injection q2w from Week 2 to Week 22 added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Dupilumab
Dupilumab 300 mg q2w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1), followed by a single 300 mg injection q2w from Week 2 to Week 22 added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: ICS/LABA therapy
Dupilumab 300 mg q2w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1), followed by a single 300 mg injection q2w from Week 2 to Week 22 added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Salbutamol/albuterol
Dupilumab 300 mg q2w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1), followed by a single 300 mg injection q2w from Week 2 to Week 22 added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Levosalbutamol/levalbuterol
Dupilumab 200 mg q2w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1), followed by a single 200 mg injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Dupilumab
Dupilumab 200 mg q2w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1), followed by a single 200 mg injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: ICS/LABA therapy
Dupilumab 200 mg q2w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1), followed by a single 200 mg injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Salbutamol/albuterol
Dupilumab 200 mg q2w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1), followed by a single 200 mg injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Levosalbutamol/levalbuterol
Dupilumab 300 mg q4w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Dupilumab
Dupilumab 300 mg q4w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: placebo
Dupilumab 300 mg q4w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: ICS/LABA therapy
Dupilumab 300 mg q4w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Salbutamol/albuterol
Dupilumab 300 mg q4w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Levosalbutamol/levalbuterol
Dupilumab 200 mg q4w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Dupilumab
Dupilumab 200 mg q4w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: placebo
Dupilumab 200 mg q4w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: ICS/LABA therapy
Dupilumab 200 mg q4w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Salbutamol/albuterol
Dupilumab 200 mg q4w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Levosalbutamol/levalbuterol
Placebo q2w
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 (Week 1) followed by a single injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: placebo
Placebo q2w
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 (Week 1) followed by a single injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: ICS/LABA therapy
Placebo q2w
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 (Week 1) followed by a single injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Salbutamol/albuterol
Placebo q2w
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 (Week 1) followed by a single injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention: Levosalbutamol/levalbuterol
Outcomes
Primary Outcomes
Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population
Time Frame: Baseline, Week 12
FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Absolute Change From Baseline in FEV1 at Week 12: ITT Population
Time Frame: Baseline, Week 12
FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Secondary Outcomes
- Annualized Event Rate of LOAC During The Treatment Period: ITT Population(Baseline to Week 24)
- Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population(Baseline, Week 12)
- Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population(Baseline up to Week 24)
- Change From Baseline in AQLQ Global Score at Week 12: ITT Population(Baseline, Week 12)
- Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population(Baseline, Week 12)
- Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population(Baseline up to Week 24)
- Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population(Baseline up to Week 24)
- Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population(Baseline to Week 24)
- Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population(Baseline, Week 12)
- Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population(Baseline to Week 24)
- Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population(Baseline, Week 12)
- Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population(Baseline, Week 12)
- Percent Change From Baseline in FEV1 at Week 12: ITT Population(Baseline, Week 12)
- Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population(Baseline to Week 24)
- Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population(Baseline up to Week 24)
- Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population(Baseline, Week 12)
- Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population(Baseline, Week 12)
- Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population(Baseline, Week 12)
- Change From Baseline in ACQ-5 Score at Week 12: ITT Population(Baseline, Week 12)
- Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population(Baseline, Week 12)