Clinical trial NCT02528214: Evaluation of Dupilumab in Patients With Severe Steroid Dependent Asthma
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Severe Steroid Dependent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2015-08-19
Enrollment: 210
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Percentage Reduction From Baseline in Oral Corticosteroids (OCS) Dose at Week 24 While Maintaining Asthma Control
timeFrame: Baseline, Week 24
measure: Supplementary Presentation of Primary Outcome Measure Data: Median Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Percentage of Participants Achieving >= 50% Reduction in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
timeFrame: Week 24
measure: Percentage of Participants Achieving a Reduction in Oral Corticosteroids Dose to <5 mg/Day at Week 24 While Maintaining Asthma Control
timeFrame: Week 24
measure: Percentage of Participants Achieving Maximum Possible Reduction in Oral Corticosteroids Dose Per Protocol at Week 24 While Maintaining Asthma Control
timeFrame: Week 24
measure: Percentage of Participants Who No Longer Required Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
timeFrame: Week 24
measure: Absolute Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
timeFrame: Baseline and Week 24
Other outcomes:
measure: Annualized Rate of Severe Exacerbation Events During The 24-Week Treatment Period
timeFrame: Baseline to Week 24
measure: Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Weeks 12 and 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in Asthma Control Questionnaire 5-Question Version (ACQ-5) Score at Weeks 2, 4, 8, 12, 16, 20, and 24
timeFrame: Baseline and at Weeks 2, 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Scores at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in Sino Nasal Outcome Test-22 (SNOT-22) Global Score at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
Locations:
city: Los Angeles
country: United States
facility: Investigational Site Number 840022
state: California
city: Rolling Hills Estates
country: United States
facility: Investigational Site Number 840014
state: California
city: Saint Louis
country: United States
facility: Investigational Site Number 840002
state: Missouri
city: Pittsburgh
country: United States
facility: Investigational Site Number 840010
state: Pennsylvania
city: Amarillo
country: United States
facility: Investigational Site Number 840062
state: Texas
city: McKinney
country: United States
facility: Investigational Site Number 840070
state: Texas
city: McKinney
country: United States
facility: Investigational Site Number 840128
state: Texas
city: Plano
country: United States
facility: Investigational Site Number 840118
state: Texas
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032003
city: Caba
country: Argentina
facility: Investigational Site Number 032001
city: Caba
country: Argentina
facility: Investigational Site Number 032091
city: Brussels
country: Belgium
facility: Investigational Site Number 056002
city: Gent
country: Belgium
facility: Investigational Site Number 056003
city: Leuven
country: Belgium
facility: Investigational Site Number 056001
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076011
city: Sorocaba
country: Brazil
facility: Investigational Site Number 076002
city: São Bernardo Do Campo
country: Brazil
facility: Investigational Site Number 076013
city: Calgary
country: Canada
facility: Investigational Site Number 124009
city: Hamilton
country: Canada
facility: Investigational Site Number 124016
city: Mississauga
country: Canada
facility: Investigational Site Number 124003
city: Ottawa
country: Canada
facility: Investigational Site Number 124013
city: Toronto
country: Canada
facility: Investigational Site Number 124002
city: Vancouver
country: Canada
facility: Investigational Site Number 124017
city: Quillota
country: Chile
facility: Investigational Site Number 152007
city: Santiago
country: Chile
facility: Investigational Site Number 152005
city: Talca
country: Chile
facility: Investigational Site Number 152008
city: Bogota
country: Colombia
facility: Investigational Site Number 170001
city: Bogota
country: Colombia
facility: Investigational Site Number 170006
city: Balassagyarmat
country: Hungary
facility: Investigational Site Number 348301
city: Edelény
country: Hungary
facility: Investigational Site Number 348303
city: Haifa
country: Israel
facility: Investigational Site Number 376003
city: Kfar Saba
country: Israel
facility: Investigational Site Number 376001
city: Petah-Tikva
country: Israel
facility: Investigational Site Number 376005
city: Rehovot
country: Israel
facility: Investigational Site Number 376002
city: Tel Hashomer
country: Israel
facility: Investigational Site Number 376004
city: Catania
country: Italy
facility: Investigational Site Number 380005
city: Genova
country: Italy
facility: Investigational Site Number 380002
city: Napoli
country: Italy
facility: Investigational Site Number 380008
city: Palermo
country: Italy
facility: Investigational Site Number 380009
city: Pisa
country: Italy
facility: Investigational Site Number 380001
city: Reggio Emilia
country: Italy
facility: Investigational Site Number 380003
city: Acapulco
country: Mexico
facility: Investigational Site Number 484016
city: Chihuahua
country: Mexico
facility: Investigational Site Number 484013
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484001
city: Mexico, Df
country: Mexico
facility: Investigational Site Number 484002
city: Monterrey
country: Mexico
facility: Investigational Site Number 484003
city: Arnhem
country: Netherlands
facility: Investigational Site Number 528001
city: Dordrecht
country: Netherlands
facility: Investigational Site Number 528002
city: Bialystok
country: Poland
facility: Investigational Site Number 616006
city: Krakow
country: Poland
facility: Investigational Site Number 616097
city: Lodz
country: Poland
facility: Investigational Site Number 616001
city: Warszawa
country: Poland
facility: Investigational Site Number 616010
city: Znin
country: Poland
facility: Investigational Site Number 616011
city: Bucharest
country: Romania
facility: Investigational Site Number 642104
city: Bucharest
country: Romania
facility: Investigational Site Number 642103
city: Cluj-Napoca
country: Romania
facility: Investigational Site Number 642102
city: Cluj-Napoca
country: Romania
facility: Investigational Site Number 642107
city: Cluj-Napoca
country: Romania
facility: Investigational Site Number 642108
city: Timisoara
country: Romania
facility: Investigational Site Number 642105
city: Timisoara
country: Romania
facility: Investigational Site Number 642106
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643006
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643007
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 643011
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643099
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643009
city: Barcelona
country: Spain
facility: Investigational Site Number 724014
city: Barcelona
country: Spain
facility: Investigational Site Number 724002
city: Madrid
country: Spain
facility: Investigational Site Number 724013
city: Pozuelo De Alarcón
country: Spain
facility: Investigational Site Number 724006
city: Sant Boi De Llobregat
country: Spain
facility: Investigational Site Number 724007
city: Santiago De Compostela
country: Spain
facility: Investigational Site Number 724096
city: Chernivtsi
country: Ukraine
facility: Investigational Site Number 804007
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number 804004
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number 804009
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 804001
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804003
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804011
city: Odessa
country: Ukraine
facility: Investigational Site Number 804006
city: Poltava
country: Ukraine
facility: Investigational Site Number 804002
city: Vinnytsya
country: Ukraine
facility: Investigational Site Number 804019
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.