Evaluation of Dupilumab in Patients With Severe Steroid Dependent Asthma

NCT ID: NCT02528214

Last Updated: 2019-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-15
• Study Completion Date: 2017-11-13

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).

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo q2w

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Oral corticosteroid therapy (prednisone/prednisolone)

Intervention Type: DRUG

Oral administration.

Inhaled corticosteroid (ICS) therapy

Intervention Type: DRUG

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

Albuterol/Salbutamol

Intervention Type: DRUG

Oral inhalation as needed.

Levalbuterol/Levosalbutamol

Intervention Type: DRUG

Oral inhalation as needed.

Dupilumab 300 mg q2w

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.

Group Type: EXPERIMENTAL

Dupilumab

Intervention Type: DRUG

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

Oral corticosteroid therapy (prednisone/prednisolone)

Intervention Type: DRUG

Oral administration.

Inhaled corticosteroid (ICS) therapy

Intervention Type: DRUG

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

Albuterol/Salbutamol

Intervention Type: DRUG

Oral inhalation as needed.

Levalbuterol/Levosalbutamol

Intervention Type: DRUG

Oral inhalation as needed.

Interventions

Dupilumab

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Oral corticosteroid therapy (prednisone/prednisolone)

Oral administration.

Intervention Type: DRUG

Inhaled corticosteroid (ICS) therapy

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

Intervention Type: DRUG

Albuterol/Salbutamol

Oral inhalation as needed.

Intervention Type: DRUG

Levalbuterol/Levosalbutamol

Oral inhalation as needed.

Intervention Type: DRUG

Other Intervention Names

REGN668; SAR231893

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840022

Los Angeles, California, United States

Investigational Site Number 840014

Rolling Hills Estates, California, United States

Investigational Site Number 840002

St Louis, Missouri, United States

Investigational Site Number 840010

Pittsburgh, Pennsylvania, United States

Investigational Site Number 840062

Amarillo, Texas, United States

Investigational Site Number 840070

McKinney, Texas, United States

Investigational Site Number 840128

McKinney, Texas, United States

Investigational Site Number 840118

Plano, Texas, United States

Investigational Site Number 032003

Buenos Aires, , Argentina

Investigational Site Number 032001

Caba, , Argentina

Investigational Site Number 032091

Caba, , Argentina

Investigational Site Number 056002

Brussels, , Belgium

Investigational Site Number 056003

Ghent, , Belgium

Investigational Site Number 056001

Leuven, , Belgium

Investigational Site Number 076013

São Bernardo do Campo, , Brazil

Investigational Site Number 076011

São Paulo, , Brazil

Investigational Site Number 076002

Sorocaba, , Brazil

Investigational Site Number 124009

Calgary, , Canada

Investigational Site Number 124016

Hamilton, , Canada

Investigational Site Number 124003

Mississauga, , Canada

Investigational Site Number 124013

Ottawa, , Canada

Investigational Site Number 124002

Toronto, , Canada

Investigational Site Number 124017

Vancouver, , Canada

Investigational Site Number 152007

Quillota, , Chile

Investigational Site Number 152005

Santiago, , Chile

Investigational Site Number 152008

Talca, , Chile

Investigational Site Number 170001

Bogotá, , Colombia

Investigational Site Number 170006

Bogotá, , Colombia

Investigational Site Number 348301

Balassagyarmat, , Hungary

Investigational Site Number 348303

Edelény, , Hungary

Investigational Site Number 376003

Haifa, , Israel

Investigational Site Number 376001

Kfar Saba, , Israel

Investigational Site Number 376005

Petah Tikva, , Israel

Investigational Site Number 376002

Rehovot, , Israel

Investigational Site Number 376004

Tel Litwinsky, , Israel

Investigational Site Number 380005

Catania, , Italy

Investigational Site Number 380002

Genova, , Italy

Investigational Site Number 380008

Napoli, , Italy

Investigational Site Number 380009

Palermo, , Italy

Investigational Site Number 380001

Pisa, , Italy

Investigational Site Number 380003

Reggio Emilia, , Italy

Investigational Site Number 484016

Acapulco, , Mexico

Investigational Site Number 484013

Chihuahua City, , Mexico

Investigational Site Number 484001

Guadalajara, , Mexico

Investigational Site Number 484002

Mexico City, , Mexico

Investigational Site Number 484003

Monterrey, , Mexico

Investigational Site Number 528001

Arnhem, , Netherlands

Investigational Site Number 528002

Dordrecht, , Netherlands

Investigational Site Number 616006

Bialystok, , Poland

Investigational Site Number 616097

Krakow, , Poland

Investigational Site Number 616001

Lodz, , Poland

Investigational Site Number 616010

Warsaw, , Poland

Investigational Site Number 616011

Żnin, , Poland

Investigational Site Number 642104

Bucharest, , Romania

Investigational Site Number 642103

Bucharest, , Romania

Investigational Site Number 642102

Cluj-Napoca, , Romania

Investigational Site Number 642107

Cluj-Napoca, , Romania

Investigational Site Number 642108

Cluj-Napoca, , Romania

Investigational Site Number 642105

Timișoara, , Romania

Investigational Site Number 642106

Timișoara, , Romania

Investigational Site Number 643006

Moscow, , Russia

Investigational Site Number 643007

Moscow, , Russia

Investigational Site Number 643099

Saint Petersburg, , Russia

Investigational Site Number 643011

Saint Petersburg, , Russia

Investigational Site Number 643009

Saint Petersburg, , Russia

Investigational Site Number 724014

Barcelona, , Spain

Investigational Site Number 724002

Barcelona, , Spain

Investigational Site Number 724013

Madrid, , Spain

Investigational Site Number 724006

Pozuelo de Alarcón, , 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 804004

Ivano-Frankivsk, , Ukraine

Investigational Site Number 804009

Ivano-Frankivsk, , Ukraine

Investigational Site Number 804001

Kharkiv, , Ukraine

Investigational Site Number 804003

Kyiv, , Ukraine

Investigational Site Number 804011

Kyiv, , Ukraine

Investigational Site Number 804006

Odesa, , Ukraine

Investigational Site Number 804002

Poltava, , Ukraine

Investigational Site Number 804019

Vinnytsia, , Ukraine

Countries

United States; Argentina; Belgium; Brazil; Canada; Chile; Colombia; Hungary; Israel; Italy; Mexico; Netherlands; Poland; Romania; Russia; Spain; Ukraine

References

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.

Reference Type: RESULT

PMID: 29782224 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36509407 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36356712 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35809937 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35636689 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35398549 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35217003 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34752208 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.ncbi.nlm.nih.gov/pubmed/?term=29782224&report=abstract

Related Info

Other Identifiers

2015-001573-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1170-7152

Identifier Type: OTHER

Identifier Source: secondary_id

EFC13691

Identifier Type: -

Identifier Source: org_study_id