Evaluation of Dupilumab in Patients With Severe Steroid Dependent Asthma

NCT02528214 | Completed Phase 3 Results DMC

• 3 other identifiers: EFC136912015-001573-40U1111-1170-7152
• Study Type: interventional
• Target: 210
• Locations: 17 countries
• Sites: 80

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• Percentage Reduction From Baseline in Oral Corticosteroids (OCS) Dose at Week 24 While Maintaining Asthma Control

  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.

  Baseline, Week 24

• Supplementary Presentation of Primary Outcome Measure Data: Median Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control

  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.

  Baseline, Week 24

Secondary Outcomes (5)

• Percentage of Participants Achieving >= 50% Reduction in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control

  Week 24

• Percentage of Participants Achieving a Reduction in Oral Corticosteroids Dose to <5 mg/Day at Week 24 While Maintaining Asthma Control

  Week 24

• Percentage of Participants Achieving Maximum Possible Reduction in Oral Corticosteroids Dose Per Protocol at Week 24 While Maintaining Asthma Control

  Week 24

• Percentage of Participants Who No Longer Required Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control

  Week 24

• Absolute Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control

  Baseline and Week 24

Other Outcomes (7)

• Annualized Rate of Severe Exacerbation Events During The 24-Week Treatment Period

  Baseline to Week 24

• Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Weeks 12 and 24

  Baseline, Week 12 and Week 24

• Change From Baseline in Asthma Control Questionnaire 5-Question Version (ACQ-5) Score at Weeks 2, 4, 8, 12, 16, 20, and 24

  Baseline and at Weeks 2, 4, 8, 12, 16, 20, and 24

Study Arms (2)

Placebo q2w

PLACEBO COMPARATOR

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.

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

Dupilumab 300 mg q2w

EXPERIMENTAL

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.

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

Interventions

Dupilumab DRUG

Solution for injection, Subcutaneous injection in the abdomen, upper thigh or upper arm.

Also known as: REGN668, SAR231893

Dupilumab 300 mg q2w

Placebo DRUG

Solution for injection, Subcutaneous injection in the abdomen, upper thigh or upper arm.

Placebo q2w

Oral corticosteroid therapy (prednisone/prednisolone) DRUG

Oral administration.

Dupilumab 300 mg q2w; Placebo q2w

Inhaled corticosteroid (ICS) therapy DRUG

Oral inhalation, stable dose (high dose) of ICS in combination with up to 2 other controller medicines (second or third controller therapy).

Dupilumab 300 mg q2w; Placebo q2w

Albuterol/Salbutamol DRUG

Oral inhalation as needed.

Dupilumab 300 mg q2w; Placebo q2w

Levalbuterol/Levosalbutamol DRUG

Oral inhalation as needed.

Dupilumab 300 mg q2w; Placebo q2w

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult and adolescent (12 years of age or older) participants with a physician diagnosis of asthma for \>=12 months, based on the Global Initiative for Asthma (GINA) 2014 guidelines and the following criteria:
• Participants with severe asthma and a well-documented, regular prescribed treatment of maintenance corticosteroids in the 6 months prior to Visit 1 and using a stable OCS dose (ie, no change of OCS dose) for 4 weeks prior to Visit 1. Participants must be taking 5 to 35 mg/day of prednisone/prednisolone, or the equivalent, at Visit 1 and at the randomization visit. In addition, the participants must agree to switch to study-required prednisone/prednisolone as their OCS and use it per protocol for the duration of the study.
• Existing treatment with high-dose inhaled corticosteroid (ICS; \>500 mcg total daily dose of fluticasone propionate or equivalent) in combination with a second controller (ie, long-acting beta agonist \[LABA\], leukotriene receptor antagonist \[LTRA\]) for at least 3 months with a stable dose of ICS for \>=1 month prior to Visit 1. In addition, participants requiring a third controller for their asthma are considered eligible for this study, and it should also be used for at least 3 months with a stable dose \>= 1 month prior to Visit 1.
• A forced expiratory volume in 1 second (FEV1) \<80% of predicted normal for adults and \<=90% of predicted normal for adolescents at Visit 1.
• Evidence of asthma as documented by either: reversibility of at least 12% and 200 mL in FEV1 after the administration of 200 to 400 mcg (2 to 4 inhalations of albuterol/salbutamol or levalbuterol/levosalbutamol, or of a nebulized solution of albuterol/salbutamol or levalbuterol/levosalbutamol, if considered as a standard office practice) before randomization or documented in the 12 months prior to Visit 1 OR airway hyperresponsiveness (methacholine: provocative concentration that causes a positive reaction \[PC20\] of \<8 mg/mL) documented in the 12 months prior to Visit 1.

You may not qualify if:

• Participants \<12 years of age or the minimum legal age for adolescents in the country of the investigative site, whichever is higher (for those countries where local regulations permit enrollment of adults only, participant recruitment will be restricted to those who were \>=18 years of age).
• Participants who weighed \<30.0 kg.
• Chronic obstructive pulmonary disease (COPD) or other lung diseases (eg, idiopathic pulmonary fibrosis, Churg-Strauss Syndrome, allergic bronchopulmonary aspergillosis, cystic fibrosis) which may impair lung function.
• Clinical evidence or imaging (eg, chest X-ray, computed tomography, magnetic resonance imaging) within 12 months of Visit 1 with clinically significant findings of lung disease(s) other than asthma, as per local standard of care.
• A participant who experiences a deterioration of asthma that results in emergency treatment or hospitalization within 4 weeks of Screening Visit 1.
• A participant who requires 12 puffs or more of rescue medication on any 1 day in the week prior to Visit 1.
• A participant who has experienced an upper or lower respiratory tract infection within the 4 weeks prior to screening.
• Current smoker or cessation of smoking within 6 months prior to Visit 1.
• Previous smoker with a smoking history \>10 pack-years.
• Comorbid disease that might interfere with the evaluation of the investigational medicinal product.
• The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (80)

Investigational Site Number 840022

Los Angeles, California, 90048, United States

Location

Investigational Site Number 840014

Rolling Hills Estates, California, 90274, United States

Location

Investigational Site Number 840002

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840010

Pittsburgh, Pennsylvania, 15213, United States

Location

Investigational Site Number 840062

Amarillo, Texas, 79106, United States

Location

Investigational Site Number 840070

McKinney, Texas, 75069, United States

Location

Investigational Site Number 840128

McKinney, Texas, 75071, United States

Location

Investigational Site Number 840118

Plano, Texas, 75093, United States

Location

Investigational Site Number 032003

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number 032001

Caba, C1425BEN, Argentina

Location

Investigational Site Number 032091

Caba, C1426ABP, Argentina

Location

Investigational Site Number 056002

Brussels, 1020, Belgium

Location

Investigational Site Number 056003

Ghent, 9000, Belgium

Location

Investigational Site Number 056001

Leuven, 3000, Belgium

Location

Investigational Site Number 076013

São Bernardo do Campo, 09780-000, Brazil

Location

Investigational Site Number 076011

São Paulo, 04020-041, Brazil

Location

Investigational Site Number 076002

Sorocaba, 18040-425, Brazil

Location

Investigational Site Number 124009

Calgary, T2N 4Z6, Canada

Location

Investigational Site Number 124016

Hamilton, L8N 4A6, Canada

Location

Investigational Site Number 124003

Mississauga, L5A 3V4, Canada

Location

Investigational Site Number 124013

Ottawa, K1G 6C6, Canada

Location

Investigational Site Number 124002

Toronto, M5T 3A9, Canada

Location

Investigational Site Number 124017

Vancouver, V6Z 1Y6, Canada

Location

Investigational Site Number 152007

Quillota, 2260877, Chile

Location

Investigational Site Number 152005

Santiago, 7500692, Chile

Location

Investigational Site Number 152008

Talca, 3460001, Chile

Location

Investigational Site Number 170001

Bogotá, 110121, Colombia

Location

Investigational Site Number 170006

Bogotá, Colombia

Location

Investigational Site Number 348301

Balassagyarmat, 2660, Hungary

Location

Investigational Site Number 348303

Edelény, 3780, Hungary

Location

Investigational Site Number 376003

Haifa, 34362, Israel

Location

Investigational Site Number 376001

Kfar Saba, 44281, Israel

Location

Investigational Site Number 376005

Petah Tikva, 49100, Israel

Location

Investigational Site Number 376002

Rehovot, 76100, Israel

Location

Investigational Site Number 376004

Tel Litwinsky, 52621, Israel

Location

Investigational Site Number 380005

Catania, 95123, Italy

Location

Investigational Site Number 380002

Genova, 16132, Italy

Location

Investigational Site Number 380008

Napoli, 80131, Italy

Location

Investigational Site Number 380009

Palermo, 90146, Italy

Location

Investigational Site Number 380001

Pisa, 56124, Italy

Location

Investigational Site Number 380003

Reggio Emilia, 42123, Italy

Location

Investigational Site Number 484016

Acapulco, 39670, Mexico

Location

Investigational Site Number 484013

Chihuahua City, 31020, Mexico

Location

Investigational Site Number 484001

Guadalajara, 44100, Mexico

Location

Investigational Site Number 484002

Mexico City, 06726, Mexico

Location

Investigational Site Number 484003

Monterrey, 64460, Mexico

Location

Investigational Site Number 528001

Arnhem, 6815 AD, Netherlands

Location

Investigational Site Number 528002

Dordrecht, 3318 AT, Netherlands

Location

Investigational Site Number 616006

Bialystok, 15-010, Poland

Location

Investigational Site Number 616097

Krakow, 31-159, Poland

Location

Investigational Site Number 616001

Lodz, 90-141, Poland

Location

Investigational Site Number 616010

Warsaw, 04-141, Poland

Location

Investigational Site Number 616011

Żnin, 88-400, Poland

Location

Investigational Site Number 642104

Bucharest, 011461, Romania

Location

Investigational Site Number 642103

Bucharest, 050159, Romania

Location

Investigational Site Number 642102

Cluj-Napoca, 400162, Romania

Location

Investigational Site Number 642107

Cluj-Napoca, 400371, Romania

Location

Investigational Site Number 642108

Cluj-Napoca, 400371, Romania

Location

Investigational Site Number 642105

Timișoara, 300310, Romania

Location

Investigational Site Number 642106

Timișoara, 300310, Romania

Location

Investigational Site Number 643006

Moscow, 105077, Russia

Location

Investigational Site Number 643007

Moscow, 117574, Russia

Location

Investigational Site Number 643099

Saint Petersburg, 193231, Russia

Location

Investigational Site Number 643011

Saint Petersburg, 194356, Russia

Location

Investigational Site Number 643009

Saint Petersburg, 197022, Russia

Location

Investigational Site Number 724014

Barcelona, 08023, Spain

Location

Investigational Site Number 724002

Barcelona, 08035, Spain

Location

Investigational Site Number 724013

Madrid, 28942, Spain

Location

Investigational Site Number 724006

Pozuelo de Alarcón, 28223, Spain

Location

Investigational Site Number 724007

Sant Boi de Llobregat, 08830, Spain

Location

Investigational Site Number 724096

Santiago de Compostela, 15706, Spain

Location

Investigational Site Number 804007

Chernivtsi, 58001, Ukraine

Location

Investigational Site Number 804004

Ivano-Frankivsk, 76018, Ukraine

Location

Investigational Site Number 804009

Ivano-Frankivsk, 76018, Ukraine

Location

Investigational Site Number 804001

Kharkiv, 61124, Ukraine

Location

Investigational Site Number 804003

Kyiv, 03680, Ukraine

Location

Investigational Site Number 804011

Kyiv, 03680, Ukraine

Location

Investigational Site Number 804006

Odesa, 65025, Ukraine

Location

Investigational Site Number 804002

Poltava, 36038, Ukraine

Location

Investigational Site Number 804019

Vinnytsia, 21001, Ukraine

Location

Related Publications (8)

• Rabe KF, Nair P, Brusselle G, Maspero JF, Castro M, Sher L, Zhu H, Hamilton JD, Swanson BN, Khan A, Chao J, Staudinger H, Pirozzi G, Antoni C, Amin N, Ruddy M, Akinlade B, Graham NMH, Stahl N, Yancopoulos GD, Teper A. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N Engl J Med. 2018 Jun 28;378(26):2475-2485. doi: 10.1056/NEJMoa1804093. Epub 2018 May 21.

  PMID: 29782224 RESULT

• Sher LD, Passalacqua G, Taille C, Cohn L, Daizadeh N, Pandit-Abid N, Soler X, Khodzhayev A, Jacob-Nara JA, Deniz Y, Rowe PJ, Nag A, Zhang Y. The long-term effect of dupilumab on dyspnea, sleep, and activity in oral corticosteroid-dependent severe asthma. Ann Allergy Asthma Immunol. 2023 Mar;130(3):298-304. doi: 10.1016/j.anai.2022.12.002. Epub 2022 Dec 9.

  PMID: 36509407 DERIVED

• Berger P, Menzies-Gow A, Peters AT, Kuna P, Rabe KF, Altincatal A, Soler X, Pandit-Abid N, Siddiqui S, Jacob-Nara JA, Deniz Y, Rowe PJ. Long-term efficacy of dupilumab in asthma with or without chronic rhinosinusitis and nasal polyps. Ann Allergy Asthma Immunol. 2023 Feb;130(2):215-224. doi: 10.1016/j.anai.2022.11.006. Epub 2022 Nov 7.

  PMID: 36356712 DERIVED

• Lugogo N, Mohan A. Are We Poised to Change the Trajectory of Maintenance Oral Corticosteroid Use in Severe Asthma in the Age of Biologics? Chest. 2022 Jul;162(1):4-5. doi: 10.1016/j.chest.2022.04.004. No abstract available.

  PMID: 35809937 DERIVED

• Wechsler ME, Klion AD, Paggiaro P, Nair P, Staumont-Salle D, Radwan A, Johnson RR, Kapoor U, Khokhar FA, Daizadeh N, Chen Z, Laws E, Ortiz B, Jacob-Nara JA, Mannent LP, Rowe PJ, Deniz Y. Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2022 Oct;10(10):2695-2709. doi: 10.1016/j.jaip.2022.05.019. Epub 2022 May 28.

  PMID: 35636689 DERIVED

• Domingo C, Maspero JF, Castro M, Hanania NA, Ford LB, Halpin DMG, Jackson DJ, Daizadeh N, Djandji M, Mitchell CP, Crikelair N, Jacob-Nara JA, Deniz Y, Rowe PJ, Ortiz B. Dupilumab Efficacy in Steroid-Dependent Severe Asthma by Baseline Oral Corticosteroid Dose. J Allergy Clin Immunol Pract. 2022 Jul;10(7):1835-1843. doi: 10.1016/j.jaip.2022.03.020. Epub 2022 Apr 8.

  PMID: 35398549 DERIVED

• Sher LD, Wechsler ME, Rabe KF, Maspero JF, Daizadeh N, Mao X, Ortiz B, Mannent LP, Laws E, Ruddy M, Pandit-Abid N, Jacob-Nara JA, Gall R, Rowe PJ, Deniz Y, Lederer DJ, Hardin M. Dupilumab Reduces Oral Corticosteroid Use in Patients With Corticosteroid-Dependent Severe Asthma: An Analysis of the Phase 3, Open-Label Extension TRAVERSE Trial. Chest. 2022 Jul;162(1):46-55. doi: 10.1016/j.chest.2022.01.071. Epub 2022 Feb 22.

  PMID: 35217003 DERIVED

• Tohda Y, Matsumoto H, Miyata M, Taguchi Y, Ueyama M, Joulain F, Arakawa I. Cost-effectiveness analysis of dupilumab among patients with oral corticosteroid-dependent uncontrolled severe asthma in Japan. J Asthma. 2022 Nov;59(11):2162-2173. doi: 10.1080/02770903.2021.1996596. Epub 2021 Dec 8.

  PMID: 34752208 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Asthma

Interventions

dupilumab; Prednisone; Prednisolone; Therapeutics; Albuterol; Levalbuterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: August 19, 2015
• Study Start: October 15, 2015
• Primary Completion: September 20, 2017
• Study Completion: November 13, 2017
• Last Updated: October 1, 2019
• Results First Posted: October 23, 2018

Record last verified: 2017-11

Locations

CL (3); CA (6); IL (5); ES (6); BE (3); IT (6); PL (5); UA (9); ME (5); HU (2); CO (2); RU (5); AR (3); NL (2); BR (3); RO (7); US (8)