Clinical trial NCT03387852: Evaluation of SAR440340 and as Combination Therapy With Dupilumab in Moderate-to-Severe Asthma Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-01-02
Enrollment: 296
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Loss of Asthma Control
timeFrame: From Baseline up to Week 12
Secondary outcomes:
measure: Change From Baseline at Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline, Week 12
measure: Change From Baseline at Week 12 in Post-bronchodilator Forced Expiratory Volume in 1 Second
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 8400026
state: Alabama
city: Long Beach
country: United States
facility: Investigational Site Number 8400004
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8400020
state: California
city: Rolling Hills Estates
country: United States
facility: Investigational Site Number 8400001
state: California
city: San Jose
country: United States
facility: Investigational Site Number 8400013
state: California
city: Stockton
country: United States
facility: Investigational Site Number 8400009
state: California
city: Colorado Springs
country: United States
facility: Investigational Site Number 8400016
state: Colorado
city: Ann Arbor
country: United States
facility: Investigational Site Number 8400021
state: Michigan
city: Minneapolis
country: United States
facility: Investigational Site Number 8400022
state: Minnesota
city: Papillion
country: United States
facility: Investigational Site Number 8400007
state: Nebraska
city: Edmond
country: United States
facility: Investigational Site Number 8400025
state: Oklahoma
city: Medford
country: United States
facility: Investigational Site Number 8400011
state: Oregon
city: Portland
country: United States
facility: Investigational Site Number 8400024
state: Oregon
city: Dallas
country: United States
facility: Investigational Site Number 8400010
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8400023
state: Texas
city: Plano
country: United States
facility: Investigational Site Number 8400006
state: Texas
city: Murray
country: United States
facility: Investigational Site Number 8400008
state: Utah
city: Milwaukee
country: United States
facility: Investigational Site Number 8400014
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 0320001
city: Caba
country: Argentina
facility: Investigational Site Number 0320003
city: Caba
country: Argentina
facility: Investigational Site Number 0320002
city: Caba
country: Argentina
facility: Investigational Site Number 0320004
city: Mendoza
country: Argentina
facility: Investigational Site Number 0320005
city: Quillota
country: Chile
facility: Investigational Site Number 1520002
city: Santiago
country: Chile
facility: Investigational Site Number 1520001
city: Santiago
country: Chile
facility: Investigational Site Number 1520009
city: Santiago
country: Chile
facility: Investigational Site Number 1520008
city: Santiago
country: Chile
facility: Investigational Site Number 1520007
city: Santiago
country: Chile
facility: Investigational Site Number 1520004
city: Talca
country: Chile
facility: Investigational Site Number 1520005
city: Viña Del Mar
country: Chile
facility: Investigational Site Number 1520003
city: Chihuahua
country: Mexico
facility: Investigational Site Number 4840005
city: Durango
country: Mexico
facility: Investigational Site Number 4840004
city: Guadalajara
country: Mexico
facility: Investigational Site Number 4840002
city: Monterrey
country: Mexico
facility: Investigational Site Number 4840006
city: Monterrey
country: Mexico
facility: Investigational Site Number 4840001
city: Veracruz
country: Mexico
facility: Investigational Site Number 4840003
city: Bialystok
country: Poland
facility: Investigational Site Number 6160001
city: Bialystok
country: Poland
facility: Investigational Site Number 6160008
city: Bydgoszcz
country: Poland
facility: Investigational Site Number 6160005
city: Krakow
country: Poland
facility: Investigational Site Number 6160007
city: Poznan
country: Poland
facility: Investigational Site Number 6160002
city: Poznan
country: Poland
facility: Investigational Site Number 6160006
city: Znin
country: Poland
facility: Investigational Site Number 6160003
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430003
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430005
city: Ryazan
country: Russian Federation
facility: Investigational Site Number 6430008
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430010
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430006
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430007
city: Stavropol
country: Russian Federation
facility: Investigational Site Number 6430009
city: Ulyanovsk
country: Russian Federation
facility: Investigational Site Number 6430004
city: Ankara
country: Turkey
facility: Investigational Site Number 7920004
city: Bursa
country: Turkey
facility: Investigational Site Number 7920003
city: Istanbul
country: Turkey
facility: Investigational Site Number 7920001
city: Izmir
country: Turkey
facility: Investigational Site Number 7920006
city: Izmir
country: Turkey
facility: Investigational Site Number 7920007
city: Kirikkale
country: Turkey
facility: Investigational Site Number 7920008
city: Mersin
country: Turkey
facility: Investigational Site Number 7920002
city: Rize
country: Turkey
facility: Investigational Site Number 7920009
city: Chernivtsi
country: Ukraine
facility: Investigational Site Number 8040008
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number 8040012
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 8040002
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 8040009
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 8040011
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8040007
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8040001
city: Odesa
country: Ukraine
facility: Investigational Site Number 8040006
city: Ternopil
country: Ukraine
facility: Investigational Site Number 8040003
city: Vinnytsya
country: Ukraine
facility: Investigational Site Number 8040005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Wechsler ME, Ruddy MK, Pavord ID, Israel E, Rabe KF, Ford LB, Maspero JF, Abdulai RM, Hu CC, Martincova R, Jessel A, Nivens MC, Amin N, Weinreich DM, Yancopoulos GD, Goulaouic H. Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma. N Engl J Med. 2021 Oct 28;385(18):1656-1668. doi: 10.1056/NEJMoa2024257.