Evaluation of Dupilumab in Patients With Severe Steroid Dependent Asthma

Phase 3

Completed

Conditions: Asthma

Interventions: Drug: Placebo
Drug: Dupilumab
Drug: Oral corticosteroid therapy (prednisone/prednisolone)
Drug: Inhaled corticosteroid (ICS) therapy
Drug: Albuterol/Salbutamol
Drug: Levalbuterol/Levosalbutamol

Registration Number: NCT02528214

Lead Sponsor: Sanofi

Brief Summary: Primary Objective:

To evaluate the efficacy of dupilumab, compared with placebo, for reducing the use of maintenance oral corticosteroids (OCS) in participants with severe steroid-dependent asthma.

Secondary Objectives:

* To evaluate the safety and tolerability of dupilumab.

* To evaluate the effect of dupilumab in improving participants-reported outcomes.

* To evaluate dupilumab systemic exposure and the incidence of treatment-emergent antidrug antibodies.

Detailed Description: The total study duration per participant was up to 46 weeks, consisting of a screening period of 3 to up to 8 weeks (up to 10 weeks for participants who experienced a clinically significant asthma exacerbation during the screening period), a randomized treatment period of up to 24 weeks, and a post-treatment period of 12 weeks.

Participants who completed treatment were considered for eligibility into the long term extension study LTS12551 (NCT02134028).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 210

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo q2w	Placebo	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable inhaled corticosteroid (ICS). OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Dupilumab 300 mg q2w	Albuterol/Salbutamol	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Placebo q2w	Levalbuterol/Levosalbutamol	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable inhaled corticosteroid (ICS). OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Dupilumab 300 mg q2w	Oral corticosteroid therapy (prednisone/prednisolone)	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Placebo q2w	Inhaled corticosteroid (ICS) therapy	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable inhaled corticosteroid (ICS). OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Dupilumab 300 mg q2w	Inhaled corticosteroid (ICS) therapy	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Placebo q2w	Oral corticosteroid therapy (prednisone/prednisolone)	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable inhaled corticosteroid (ICS). OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Placebo q2w	Albuterol/Salbutamol	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable inhaled corticosteroid (ICS). OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Dupilumab 300 mg q2w	Levalbuterol/Levosalbutamol	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Dupilumab 300 mg q2w	Dupilumab	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.

Primary Outcome Measures

Name	Time	Method
Percentage Reduction From Baseline in Oral Corticosteroids (OCS) Dose at Week 24 While Maintaining Asthma Control	Baseline, Week 24	Percentage reduction of OCS dose was calculated as (optimized OCS dose \[mg/day\] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100. Result is presented as Least Squares Mean (Standard Error) percentage reduction from baseline derived from ANCOVA model with missing data multiply imputed.
Supplementary Presentation of Primary Outcome Measure Data: Median Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control	Baseline, Week 24	The Primary Outcome Measure (Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control) is summarized above, as LS Mean (SE). Table below provides a supplementary presentation of the Primary Outcome Measure data; result is presented as median (inter-quartile range). Percentage reduction of OCS dose was calculated as (optimized OCS dose \[mg/day\] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Maximum Possible Reduction in Oral Corticosteroids Dose Per Protocol at Week 24 While Maintaining Asthma Control	Week 24	For all participants except those with baseline OCS dose at 35 mg/day, the maximum possible reduction corresponds to reduction to 0 mg/day (no longer requiring OCS). For participants starting with 35 mg/day at baseline, the maximum possible reduction is 32.5 mg/day (i.e. minimum dose per protocol is 2.5 mg).
Percentage of Participants Achieving >= 50% Reduction in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control	Week 24	Participants were classified according to the binary status of whether or not the 50% OCS dose reduction criterion was achieved at week 24.
Absolute Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control	Baseline and Week 24	Absolute reduction was calculated by subtracting Week 24 value from baseline value.
Percentage of Participants Achieving a Reduction in Oral Corticosteroids Dose to <5 mg/Day at Week 24 While Maintaining Asthma Control	Week 24	Participants were classified according to the binary status of whether or not the reduction of OCS dose to \<5 mg/day was achieved at Week 24.
Percentage of Participants Who No Longer Required Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control	Week 24	Participants were classified according to the binary status of whether or not the participant still required OCS at Week 24 while maintaining asthma control.

Trial Locations

Locations (80): Investigational Site Number 840022
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Los Angeles, California, United States
Investigational Site Number 840014
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Rolling Hills Estates, California, United States
Investigational Site Number 840002
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Saint Louis, Missouri, United States
Investigational Site Number 840010
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Pittsburgh, Pennsylvania, United States
Investigational Site Number 840062
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Amarillo, Texas, United States
Investigational Site Number 840070
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McKinney, Texas, United States
Investigational Site Number 840128
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McKinney, Texas, United States
Investigational Site Number 840118
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Plano, Texas, United States
Investigational Site Number 032003
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Buenos Aires, Argentina
Investigational Site Number 032001
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Caba, Argentina
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Investigational Site Number 840022
🇺🇸Los Angeles, California, United States