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

NCT03387852 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: ACT151022017-003289-29U1111-1194-2185
• Study Type: interventional
• Target: 296
• Locations: 8 countries
• Sites: 71

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Change From Baseline at Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)

  Baseline, Week 12

• Change From Baseline at Week 12 in Post-bronchodilator Forced Expiratory Volume in 1 Second

  Baseline, Week 12

Study Arms (4)

SAR440340

EXPERIMENTAL

Participants received 2 injections of SAR440340 300 milligram (mg) along with 1 injection of dupilumab placebo, subcutaneous (SC) once every 2 weeks (Q2W) for 12 weeks.

Drug: SAR440340; Drug: Fluticasone or Fluticasone/salmeterol combination; Drug: Placebo for dupilumab

Dupilumab

ACTIVE COMPARATOR

Participants received 1 injection of dupilumab 300 mg along with 2 injections of SAR440340 placebo, SC Q2W for 12 weeks.

Drug: Dupilumab; Drug: Fluticasone or Fluticasone/salmeterol combination; Drug: Placebo for SAR440340

SAR440340 + Dupilumab

EXPERIMENTAL

Participants received 2 injections of SAR440340 300 mg along with 1 injection of dupilumab 300 mg, SC Q2W for 12 weeks.

Drug: SAR440340; Drug: Dupilumab; Drug: Fluticasone or Fluticasone/salmeterol combination

Placebo

PLACEBO COMPARATOR

Participants received 2 SC injections of SAR440340 placebo along with 1 SC injection of dupilumab placebo Q2W for 12 weeks.

Drug: Fluticasone or Fluticasone/salmeterol combination; Drug: Placebo for SAR440340; Drug: Placebo for dupilumab

Interventions

SAR440340 DRUG

Pharmaceutical form: Solution for Injection, Route of administration: SC

Also known as: REGN3500

SAR440340; SAR440340 + Dupilumab

Dupilumab DRUG

Pharmaceutical form: Solution for Injection, Route of administration: SC

Also known as: SAR231893 (REGN668)

Dupilumab; SAR440340 + Dupilumab

Fluticasone or Fluticasone/salmeterol combination DRUG

Pharmaceutical form: Aerosol, dry powder, Route of administration: Inhaled

Dupilumab; Placebo; SAR440340; SAR440340 + Dupilumab

Placebo for SAR440340 DRUG

Pharmaceutical form: Solution for Injection, Route of administration: SC

Dupilumab; Placebo

Placebo for dupilumab DRUG

Pharmaceutical form: Solution for Injection, Route of administration: SC

Placebo; SAR440340

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (71)

Investigational Site Number 8400026

Birmingham, Alabama, 35209, United States

Location

Investigational Site Number 8400004

Long Beach, California, 90808, United States

Location

Investigational Site Number 8400020

Los Angeles, California, 90025, United States

Location

Investigational Site Number 8400001

Rolling Hills Estates, California, 90274, United States

Location

Investigational Site Number 8400013

San Jose, California, 95117, United States

Location

Investigational Site Number 8400009

Stockton, California, 95207, United States

Location

Investigational Site Number 8400016

Colorado Springs, Colorado, 80907, United States

Location

Investigational Site Number 8400021

Ann Arbor, Michigan, 48109, United States

Location

Investigational Site Number 8400022

Minneapolis, Minnesota, 55402, United States

Location

Investigational Site Number 8400007

Papillion, Nebraska, 27103, United States

Location

Investigational Site Number 8400025

Edmond, Oklahoma, 73034, United States

Location

Investigational Site Number 8400011

Medford, Oregon, 97504, United States

Location

Investigational Site Number 8400024

Portland, Oregon, 97209, United States

Location

Investigational Site Number 8400010

Dallas, Texas, 75231, United States

Location

Investigational Site Number 8400023

Dallas, Texas, 75231, United States

Location

Investigational Site Number 8400006

Plano, Texas, 75093, United States

Location

Investigational Site Number 8400008

Murray, Utah, 84107, United States

Location

Investigational Site Number 8400014

Milwaukee, Wisconsin, 53219, United States

Location

Investigational Site Number 0320001

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number 0320003

Caba, C1122AAK, Argentina

Location

Investigational Site Number 0320002

Caba, C1425BEN, Argentina

Location

Investigational Site Number 0320004

Caba, C1425FVH, Argentina

Location

Investigational Site Number 0320005

Mendoza, 5500, Argentina

Location

Investigational Site Number 1520002

Quillota, 2260877, Chile

Location

Investigational Site Number 1520001

Santiago, 7500692, Chile

Location

Investigational Site Number 1520009

Santiago, 7500710, Chile

Location

Investigational Site Number 1520008

Santiago, 8207257, Chile

Location

Investigational Site Number 1520007

Santiago, 8330336, Chile

Location

Investigational Site Number 1520004

Santiago, 8910131, Chile

Location

Investigational Site Number 1520005

Talca, Chile

Location

Investigational Site Number 1520003

Viña del Mar, Chile

Location

Investigational Site Number 4840005

Chihuahua City, 31000, Mexico

Location

Investigational Site Number 4840004

Durango, 34080, Mexico

Location

Investigational Site Number 4840002

Guadalajara, 44100, Mexico

Location

Investigational Site Number 4840006

Monterrey, 64460, Mexico

Location

Investigational Site Number 4840001

Monterrey, 66465, Mexico

Location

Investigational Site Number 4840003

Veracruz, 91910, Mexico

Location

Investigational Site Number 6160001

Bialystok, 15-010, Poland

Location

Investigational Site Number 6160008

Bialystok, 15-044, Poland

Location

Investigational Site Number 6160005

Bydgoszcz, 85-079, Poland

Location

Investigational Site Number 6160007

Krakow, 31-559, Poland

Location

Investigational Site Number 6160002

Poznan, 60-693, Poland

Location

Investigational Site Number 6160006

Poznan, 60-823, Poland

Location

Investigational Site Number 6160003

Żnin, 88-400, Poland

Location

Investigational Site Number 6430003

Moscow, 109240, Russia

Location

Investigational Site Number 6430001

Moscow, 109544, Russia

Location

Investigational Site Number 6430005

Moscow, 115280, Russia

Location

Investigational Site Number 6430008

Ryazan, 390039, Russia

Location

Investigational Site Number 6430007

Saint Petersburg, 193231, Russia

Location

Investigational Site Number 6430010

Saint Petersburg, 194291, Russia

Location

Investigational Site Number 6430006

Saint Petersburg, 194354, Russia

Location

Investigational Site Number 6430009

Stavropol, 355030, Russia

Location

Investigational Site Number 6430004

Ulyanovsk, 432017, Russia

Location

Investigational Site Number 7920004

Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number 7920003

Bursa, 16059, Turkey (Türkiye)

Location

Investigational Site Number 7920001

Istanbul, 34098, Turkey (Türkiye)

Location

Investigational Site Number 7920006

Izmir, 35040, Turkey (Türkiye)

Location

Investigational Site Number 7920007

Izmir, 35110, Turkey (Türkiye)

Location

Investigational Site Number 7920008

Kırıkkale, 71450, Turkey (Türkiye)

Location

Investigational Site Number 7920002

Mersin, 33070, Turkey (Türkiye)

Location

Investigational Site Number 7920009

Rize, 53100, Turkey (Türkiye)

Location

Investigational Site Number 8040008

Chernivtsi, 58001, Ukraine

Location

Investigational Site Number 8040012

Ivano-Frankivsk, 76000, Ukraine

Location

Investigational Site Number 8040002

Kharkiv, 61039, Ukraine

Location

Investigational Site Number 8040009

Kharkiv, 61124, Ukraine

Location

Investigational Site Number 8040011

Kharkiv, 61166, Ukraine

Location

Investigational Site Number 8040007

Kyiv, 02091, Ukraine

Location

Investigational Site Number 8040001

Kyiv, 02125, Ukraine

Location

Investigational Site Number 8040006

Odesa, 65025, Ukraine

Location

Investigational Site Number 8040003

Ternopil, 46000, Ukraine

Location

Investigational Site Number 8040005

Vinnytsia, 21001, Ukraine

Location

Related Publications (2)

• Yin Z, Zhou Y, Turnquist HR, Liu Q. Neuro-epithelial-ILC2 crosstalk in barrier tissues. Trends Immunol. 2022 Nov;43(11):901-916. doi: 10.1016/j.it.2022.09.006. Epub 2022 Oct 14.

  PMID: 36253275 DERIVED

• 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.

  PMID: 34706171 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

itepekimab; dupilumab; Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fluticasone; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

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 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2017
• First Posted: January 2, 2018
• Study Start: March 12, 2018
• Primary Completion: March 21, 2019
• Study Completion: August 7, 2019
• Last Updated: June 14, 2022
• Results First Posted: March 29, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

TU (8); CL (8); AR (5); RU (9); US (18); UA (10); ME (6); PL (7)