Evaluation of SAR440340 and as Combination Therapy With Dupilumab in Moderate-to-Severe Asthma Participants

Asthma Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel-group, 12-week Proof-of-Concept (PoC) Study to Assess the Efficacy, Safety, and Tolerability of SAR440340 and the Coadministration of SAR440340 and Dupilumab in Patients With Moderate-to-Severe Asthma Who Are Not Well Controlled on Inhaled Corticosteroid (ICS) Plus Long-acting β2 Adrenergic Agonist (LABA) Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03387852
• Other study ID #: ACT15102
• Secondary ID: 2017-003289-29U1
• Status: Completed
• Phase: Phase 2
• Start date: March 12, 2018
• Est. completion date: August 7, 2019

Study information

• Verified date: May 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective: To evaluate the effects of SAR440340 with or without dupilumab, compared to placebo, on reducing the incidence of "loss of asthma control" (LOAC) events. Secondary Objectives: To evaluate the effects of SAR440340/REGN3500 and coadministration of SAR440340 and dupilumab, compared with placebo, on forced expiratory volume in 1 second (FEV1). To evaluate the effects of coadministration of SAR440340 and dupilumab, compared with SAR440340 and compared with dupilumab, on FEV1. To assess safety and tolerability of SAR440340 alone and in coadministration with dupilumab.

Description:

The total duration of the study (per participant) was approximately 36 weeks, including 4 weeks screening, 12 weeks treatment, and 20 weeks post-treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 296
• Est. completion date: August 7, 2019
• Est. primary completion date: March 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria :

• Adult participants with a physician diagnosis of asthma for at least 12 months based on the Global Initiative for Asthma (GINA) 2017 Guidelines.
• Participants with existing treatment with medium to high dose ICS (greater than or equal to [>=] 250 microgram (mcg) of fluticasone propionate twice a day (BID) or equipotent ICS daily dosage to a maximum of 2000 mcg/day of fluticasone propionate or clinically comparable) in combination with a LABA as second controller for at least 3 months with a stable dose >=1 month prior to Visit 1.
• Participants with pre-bronchodilator FEV1 greater than (>) 40 percent (%) of predicted normal at Visit 1/Screening. Pre-bronchodilator FEV1 >=50% but less than or equal to (<=) 85% of predicted normal at Visit 2/Baseline.
• Participants with reversibility of at least 12% and 200 milliliters (mL) in FEV1 after administration of 2 to 4 puffs (200-400 microgram [µg]) of albuterol/salbutamol or levalbuterol/levosalbutamol during screening or documented history of a reversibility test that meets this criteria within 12 months prior to Visit 1 or documented positive response to methacholine challenge (a decrease in FEV by 20% [PC20] of less than [<] 8 milligram per milliliter [mg/mL]) within 12 months prior to Visit 1/Screening is considered acceptable to meet this inclusion criterion.
• Participants had experienced, within 1 year prior to Visit 1, any of the following

events at least once:

• Treatment with a systemic steroid (oral or parenteral) for worsening asthma.
• Hospitalization or emergency medical care visit for worsening asthma.
• Signed written informed consent.

Exclusion criteria:

• Participants <18 years or >70 years of age (i.e., have reached the age of 71 at the screening visit).
• Participants with body mass index (BMI) <16.
• Chronic lung disease (for example, chronic obstructive pulmonary disease [COPD], or idiopathic pulmonary fibrosis [IPF]), which might impair lung function.
• History of life threatening asthma (i.e., severe exacerbation that required intubation).
• Co-morbid disease that might interfere with the evaluation of investigational medicinal product (IMP).
• Participants with any of the following events within the 4 weeks prior to their

Screening Visit 1:

• Treatment with 1 or more systemic (oral and/or parenteral) steroid bursts for worsening asthma;
• Hospitalization or emergency medical care visit for worsening asthma.
• Asthma Control Questionnaire 5-question version (ACQ-5) score <1.25 or >3.0 at Visit 2/randomization. During the screening period, an ACQ-5 of up to <=4 was acceptable.
• Anti-immunoglobulin E (IgE) therapy (e.g., omalizumab [Xolair®]) within 130 days prior to Visit 1 or any other biologic therapy (including anti interleukin-5 [anti-IL5] monoclonal antibodies [mAb]) or systemic immunosuppressant (e.g., methotrexate) to treat inflammatory disease or autoimmune disease (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc.) and other diseases, within 2 months or 5 half-lives prior to Visit 1, whichever was longer.
• Participants with a history of a systemic hypersensitivity reaction to a biologic drug.
• Participants on or initiation of bronchial thermoplasty within 2 years prior to Visit 1 or plan to begin therapy during the screening period or the randomized treatment period.
• Current smoker or cessation of smoking within the 6 months prior to Visit 1.
• Previous smoker with a smoking history >10 pack-years. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• SAR440340
Pharmaceutical form: Solution for Injection, Route of administration: SC
• Dupilumab
Pharmaceutical form: Solution for Injection, Route of administration: SC
• Fluticasone or Fluticasone/salmeterol combination
Pharmaceutical form: Aerosol, dry powder, Route of administration: Inhaled
• Placebo for SAR440340
Pharmaceutical form: Solution for Injection, Route of administration: SC
• Placebo for dupilumab
Pharmaceutical form: Solution for Injection, Route of administration: SC

Locations

Country	Name	City	State
Argentina	Investigational Site Number 0320001	Buenos Aires
Argentina	Investigational Site Number 0320002	Caba
Argentina	Investigational Site Number 0320003	Caba
Argentina	Investigational Site Number 0320004	Caba
Argentina	Investigational Site Number 0320005	Mendoza
Chile	Investigational Site Number 1520002	Quillota
Chile	Investigational Site Number 1520001	Santiago
Chile	Investigational Site Number 1520004	Santiago
Chile	Investigational Site Number 1520007	Santiago
Chile	Investigational Site Number 1520008	Santiago
Chile	Investigational Site Number 1520009	Santiago
Chile	Investigational Site Number 1520005	Talca
Chile	Investigational Site Number 1520003	Viña Del Mar
Mexico	Investigational Site Number 4840005	Chihuahua
Mexico	Investigational Site Number 4840004	Durango
Mexico	Investigational Site Number 4840002	Guadalajara
Mexico	Investigational Site Number 4840001	Monterrey
Mexico	Investigational Site Number 4840006	Monterrey
Mexico	Investigational Site Number 4840003	Veracruz
Poland	Investigational Site Number 6160001	Bialystok
Poland	Investigational Site Number 6160008	Bialystok
Poland	Investigational Site Number 6160005	Bydgoszcz
Poland	Investigational Site Number 6160007	Krakow
Poland	Investigational Site Number 6160002	Poznan
Poland	Investigational Site Number 6160006	Poznan
Poland	Investigational Site Number 6160003	Znin
Russian Federation	Investigational Site Number 6430001	Moscow
Russian Federation	Investigational Site Number 6430003	Moscow
Russian Federation	Investigational Site Number 6430005	Moscow
Russian Federation	Investigational Site Number 6430008	Ryazan
Russian Federation	Investigational Site Number 6430006	Saint-Petersburg
Russian Federation	Investigational Site Number 6430010	Saint-Petersburg
Russian Federation	Investigational Site Number 6430007	St-Petersburg
Russian Federation	Investigational Site Number 6430009	Stavropol
Russian Federation	Investigational Site Number 6430004	Ulyanovsk
Turkey	Investigational Site Number 7920004	Ankara
Turkey	Investigational Site Number 7920003	Bursa
Turkey	Investigational Site Number 7920001	Istanbul
Turkey	Investigational Site Number 7920006	Izmir
Turkey	Investigational Site Number 7920007	Izmir
Turkey	Investigational Site Number 7920008	Kirikkale
Turkey	Investigational Site Number 7920002	Mersin
Turkey	Investigational Site Number 7920009	Rize
Ukraine	Investigational Site Number 8040008	Chernivtsi
Ukraine	Investigational Site Number 8040012	Ivano-Frankivsk
Ukraine	Investigational Site Number 8040002	Kharkiv
Ukraine	Investigational Site Number 8040009	Kharkiv
Ukraine	Investigational Site Number 8040011	Kharkiv
Ukraine	Investigational Site Number 8040001	Kyiv
Ukraine	Investigational Site Number 8040007	Kyiv
Ukraine	Investigational Site Number 8040006	Odesa
Ukraine	Investigational Site Number 8040003	Ternopil
Ukraine	Investigational Site Number 8040005	Vinnytsya
United States	Investigational Site Number 8400021	Ann Arbor	Michigan
United States	Investigational Site Number 8400026	Birmingham	Alabama
United States	Investigational Site Number 8400016	Colorado Springs	Colorado
United States	Investigational Site Number 8400010	Dallas	Texas
United States	Investigational Site Number 8400023	Dallas	Texas
United States	Investigational Site Number 8400025	Edmond	Oklahoma
United States	Investigational Site Number 8400004	Long Beach	California
United States	Investigational Site Number 8400020	Los Angeles	California
United States	Investigational Site Number 8400011	Medford	Oregon
United States	Investigational Site Number 8400014	Milwaukee	Wisconsin
United States	Investigational Site Number 8400022	Minneapolis	Minnesota
United States	Investigational Site Number 8400008	Murray	Utah
United States	Investigational Site Number 8400007	Papillion	Nebraska
United States	Investigational Site Number 8400006	Plano	Texas
United States	Investigational Site Number 8400024	Portland	Oregon
United States	Investigational Site Number 8400001	Rolling Hills Estates	California
United States	Investigational Site Number 8400013	San Jose	California
United States	Investigational Site Number 8400009	Stockton	California

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Mexico,  Poland,  Russian Federation,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Loss of Asthma Control	An LOAC event during the 12-week treatment period was a deterioration of asthma defined as any of the following: a) 30 percent (%) or greater reduction from baseline in morning peak expiratory flow (PEF) on 2 consecutive days; b) greater than or equal to (>=) 6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in a 24-hour period (compared to baseline) on 2 consecutive days; c) increase in inhaled corticosteroid (ICS) >=4 times the last prescribed ICS dose (or >=50% of the prescribed ICS dose at Baseline if background therapy withdrawal completed); d) required use of systemic (oral and/or parenteral) steroid treatment; e) required hospitalization or emergency room visit.	From Baseline up to Week 12
Secondary	Change From Baseline at Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Pre-bronchodilator FEV1 refers to the spirometry performed after a wash period of bronchodilators (i.e., not earlier than 6 hours) after the last dose of albuterol/salbutamol or levalbuterol/levosalbutamol from a primed meter dose inhaler and withholding the last dose of long-acting ß2 adrenergic agonist (LABA) for at least 12 hours, and prior to administration of study drug.	Baseline, Week 12
Secondary	Change From Baseline at Week 12 in Post-bronchodilator Forced Expiratory Volume in 1 Second	FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Post-bronchodilator FEV1 refers to the spirometry performed within 30 minutes after administration of bronchodilator.	Baseline, Week 12