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).

Study Timeline

• Study First Submitted: 2015-08-18
• Study First Submitted QC: 2015-08-18
• Study First Posted: 2015-08-19
• Study Start: 2015-10-15
• Primary Completion: 2017-09-20
• Status Verified: 2017-11
• Study Completion: 2017-11-13
• Results First Submitted: 2018-07-27
• Results First Submitted QC: 2018-10-19
• Results First Posted: 2018-10-23
• Last Update Submitted: 2019-09-18
• Last Update Posted: 2019-10-01

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 724014; 🇪🇸 Barcelona, Spain

Investigational Site Number 724006; 🇪🇸 Pozuelo De Alarcón, Spain

Investigational Site Number 032001; 🇦🇷 Caba, Argentina

Investigational Site Number 032003; 🇦🇷 Buenos Aires, Argentina

Investigational Site Number 056003; 🇧🇪 Gent, Belgium

Investigational Site Number 056001; 🇧🇪 Leuven, Belgium

Investigational Site Number 076002; 🇧🇷 Sorocaba, Brazil

Investigational Site Number 170006; 🇨🇴 Bogota, Colombia

Investigational Site Number 348303; 🇭🇺 Edelény, Hungary

Investigational Site Number 348301; 🇭🇺 Balassagyarmat, Hungary

Investigational Site Number 376002; 🇮🇱 Rehovot, Israel

Investigational Site Number 840022; 🇺🇸 Los Angeles, California, United States

Investigational Site Number 840010; 🇺🇸 Pittsburgh, Pennsylvania, United States

Investigational Site Number 840014; 🇺🇸 Rolling Hills Estates, California, United States

Investigational Site Number 840002; 🇺🇸 Saint Louis, Missouri, United States

Investigational Site Number 840062; 🇺🇸 Amarillo, Texas, United States

Investigational Site Number 840070; 🇺🇸 McKinney, Texas, United States

Investigational Site Number 840118; 🇺🇸 Plano, Texas, United States

Investigational Site Number 840128; 🇺🇸 McKinney, Texas, United States

Investigational Site Number 032091; 🇦🇷 Caba, Argentina

Investigational Site Number 056002; 🇧🇪 Brussels, Belgium

Investigational Site Number 076011; 🇧🇷 Sao Paulo, Brazil

Investigational Site Number 076013; 🇧🇷 São Bernardo Do Campo, Brazil

Investigational Site Number 124003; 🇨🇦 Mississauga, Canada

Investigational Site Number 124013; 🇨🇦 Ottawa, Canada

Investigational Site Number 124016; 🇨🇦 Hamilton, Canada

Investigational Site Number 124009; 🇨🇦 Calgary, Canada

Investigational Site Number 124017; 🇨🇦 Vancouver, Canada

Investigational Site Number 124002; 🇨🇦 Toronto, Canada

Investigational Site Number 152007; 🇨🇱 Quillota, Chile

Investigational Site Number 152005; 🇨🇱 Santiago, Chile

Investigational Site Number 152008; 🇨🇱 Talca, Chile

Investigational Site Number 170001; 🇨🇴 Bogota, Colombia

Investigational Site Number 376003; 🇮🇱 Haifa, Israel

Investigational Site Number 376001; 🇮🇱 Kfar Saba, Israel

Investigational Site Number 376005; 🇮🇱 Petah-Tikva, Israel

Investigational Site Number 376004; 🇮🇱 Tel Hashomer, Israel

Investigational Site Number 380005; 🇮🇹 Catania, Italy

Investigational Site Number 380002; 🇮🇹 Genova, Italy

Investigational Site Number 528002; 🇳🇱 Dordrecht, Netherlands

Investigational Site Number 380001; 🇮🇹 Pisa, Italy

Investigational Site Number 380008; 🇮🇹 Napoli, Italy

Investigational Site Number 380009; 🇮🇹 Palermo, Italy

Investigational Site Number 380003; 🇮🇹 Reggio Emilia, Italy

Investigational Site Number 484016; 🇲🇽 Acapulco, Mexico

Investigational Site Number 484001; 🇲🇽 Guadalajara, Mexico

Investigational Site Number 484013; 🇲🇽 Chihuahua, Mexico

Investigational Site Number 528001; 🇳🇱 Arnhem, Netherlands

Investigational Site Number 484002; 🇲🇽 Mexico, Df, Mexico

Investigational Site Number 484003; 🇲🇽 Monterrey, Mexico

Investigational Site Number 616006; 🇵🇱 Bialystok, Poland

Investigational Site Number 616097; 🇵🇱 Krakow, Poland

Investigational Site Number 616001; 🇵🇱 Lodz, Poland

Investigational Site Number 642104; 🇷🇴 Bucharest, Romania

Investigational Site Number 642108; 🇷🇴 Cluj-Napoca, Romania

Investigational Site Number 616010; 🇵🇱 Warszawa, Poland

Investigational Site Number 616011; 🇵🇱 Znin, Poland

Investigational Site Number 642103; 🇷🇴 Bucharest, Romania

Investigational Site Number 642107; 🇷🇴 Cluj-Napoca, Romania

Investigational Site Number 642105; 🇷🇴 Timisoara, Romania

Investigational Site Number 642102; 🇷🇴 Cluj-Napoca, Romania

Investigational Site Number 642106; 🇷🇴 Timisoara, Romania

Investigational Site Number 643006; 🇷🇺 Moscow, Russian Federation

Investigational Site Number 643011; 🇷🇺 Saint-Petersburg, Russian Federation

Investigational Site Number 643007; 🇷🇺 Moscow, Russian Federation

Investigational Site Number 643099; 🇷🇺 St-Petersburg, Russian Federation

Investigational Site Number 643009; 🇷🇺 St-Petersburg, Russian Federation

Investigational Site Number 724002; 🇪🇸 Barcelona, Spain

Investigational Site Number 724013; 🇪🇸 Madrid, Spain

Investigational Site Number 724007; 🇪🇸 Sant Boi De Llobregat, Spain

Investigational Site Number 724096; 🇪🇸 Santiago De Compostela, Spain

Investigational Site Number 804007; 🇺🇦 Chernivtsi, Ukraine

Investigational Site Number 804009; 🇺🇦 Ivano-Frankivsk, Ukraine

Investigational Site Number 804004; 🇺🇦 Ivano-Frankivsk, Ukraine

Investigational Site Number 804019; 🇺🇦 Vinnytsya, Ukraine

Investigational Site Number 804003; 🇺🇦 Kyiv, Ukraine

Investigational Site Number 804001; 🇺🇦 Kharkiv, Ukraine

Investigational Site Number 804011; 🇺🇦 Kyiv, Ukraine

Investigational Site Number 804006; 🇺🇦 Odessa, Ukraine

Investigational Site Number 804002; 🇺🇦 Poltava, Ukraine