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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: SAR440340; Drug: Fluticasone or Fluticasone/salmeterol combination; Drug: Placebo for dupilumab; Drug: Dupilumab; Drug: Placebo for SAR440340

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.

• Study Type: Interventional
• Enrollment (Actual): 296
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1121ABE
    • Investigational Site Number 0320001
  • Caba, Argentina, C1122AAK
    • Investigational Site Number 0320003
  • Caba, Argentina, C1425BEN
    • Investigational Site Number 0320002
  • Caba, Argentina, C1425FVH
    • Investigational Site Number 0320004
  • Mendoza, Argentina, 5500
    • Investigational Site Number 0320005
• Chile
  • Quillota, Chile, 2260877
    • Investigational Site Number 1520002
  • Santiago, Chile, 7500692
    • Investigational Site Number 1520001
  • Santiago, Chile, 7500710
    • Investigational Site Number 1520009
  • Santiago, Chile, 8207257
    • Investigational Site Number 1520008
  • Santiago, Chile, 8330336
    • Investigational Site Number 1520007
  • Santiago, Chile, 8910131
    • Investigational Site Number 1520004
  • Talca, Chile
    • Investigational Site Number 1520005
  • Viña Del Mar, Chile
    • Investigational Site Number 1520003
• Mexico
  • Chihuahua, Mexico, 31000
    • Investigational Site Number 4840005
  • Durango, Mexico, 34080
    • Investigational Site Number 4840004
  • Guadalajara, Mexico, 44100
    • Investigational Site Number 4840002
  • Monterrey, Mexico, 64460
    • Investigational Site Number 4840006
  • Monterrey, Mexico, 66465
    • Investigational Site Number 4840001
  • Veracruz, Mexico, 91910
    • Investigational Site Number 4840003
• Poland
  • Bialystok, Poland, 15-010
    • Investigational Site Number 6160001
  • Bialystok, Poland, 15-044
    • Investigational Site Number 6160008
  • Bydgoszcz, Poland, 85-079
    • Investigational Site Number 6160005
  • Krakow, Poland, 31-559
    • Investigational Site Number 6160007
  • Poznan, Poland, 60-693
    • Investigational Site Number 6160002
  • Poznan, Poland, 60-823
    • Investigational Site Number 6160006
  • Znin, Poland, 88-400
    • Investigational Site Number 6160003
• Russian Federation
  • Moscow, Russian Federation, 109240
    • Investigational Site Number 6430003
  • Moscow, Russian Federation, 109544
    • Investigational Site Number 6430001
  • Moscow, Russian Federation, 115280
    • Investigational Site Number 6430005
  • Ryazan, Russian Federation, 390039
    • Investigational Site Number 6430008
  • Saint-Petersburg, Russian Federation, 194291
    • Investigational Site Number 6430010
  • Saint-Petersburg, Russian Federation, 194354
    • Investigational Site Number 6430006
  • St-Petersburg, Russian Federation, 193231
    • Investigational Site Number 6430007
  • Stavropol, Russian Federation, 355030
    • Investigational Site Number 6430009
  • Ulyanovsk, Russian Federation, 432017
    • Investigational Site Number 6430004
• Turkey
  • Ankara, Turkey, 06100
    • Investigational Site Number 7920004
  • Bursa, Turkey, 16059
    • Investigational site number 7920003
  • Istanbul, Turkey, 34098
    • Investigational Site Number 7920001
  • Izmir, Turkey, 35040
    • Investigational Site Number 7920006
  • Izmir, Turkey, 35110
    • Investigational Site Number 7920007
  • Kirikkale, Turkey, 71450
    • Investigational site number 7920008
  • Mersin, Turkey, 33070
    • Investigational Site Number 7920002
  • Rize, Turkey, 53100
    • Investigational Site Number 7920009
• Ukraine
  • Chernivtsi, Ukraine, 58001
    • Investigational Site Number 8040008
  • Ivano-Frankivsk, Ukraine, 76000
    • Investigational Site Number 8040012
  • Kharkiv, Ukraine, 61039
    • Investigational Site Number 8040002
  • Kharkiv, Ukraine, 61124
    • Investigational Site Number 8040009
  • Kharkiv, Ukraine, 61166
    • Investigational Site Number 8040011
  • Kyiv, Ukraine, 02125
    • Investigational Site Number 8040001
  • Kyiv, Ukraine, 02091
    • Investigational Site Number 8040007
  • Odesa, Ukraine, 65025
    • Investigational Site Number 8040006
  • Ternopil, Ukraine, 46000
    • Investigational Site Number 8040003
  • Vinnytsya, Ukraine, 21001
    • Investigational Site Number 8040005
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Investigational Site Number 8400026
  • California
    • Long Beach, California, United States, 90808
      • Investigational Site Number 8400004
    • Los Angeles, California, United States, 90025
      • Investigational Site Number 8400020
    • Rolling Hills Estates, California, United States, 90274
      • Investigational Site Number 8400001
    • San Jose, California, United States, 95117
      • Investigational Site Number 8400013
    • Stockton, California, United States, 95207
      • Investigational Site Number 8400009
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Investigational Site Number 8400016
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Investigational Site Number 8400021
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Investigational Site Number 8400022
  • Nebraska
    • Papillion, Nebraska, United States, 27103
      • Investigational Site Number 8400007
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • Investigational Site Number 8400025
  • Oregon
    • Medford, Oregon, United States, 97504
      • Investigational Site Number 8400011
    • Portland, Oregon, United States, 97209
      • Investigational Site Number 8400024
  • Texas
    • Dallas, Texas, United States, 75231
      • Investigational Site Number 8400010
    • Dallas, Texas, United States, 75231
      • Investigational Site Number 8400023
    • Plano, Texas, United States, 75093
      • Investigational Site Number 8400006
  • Utah
    • Murray, Utah, United States, 84107
      • Investigational Site Number 8400008
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53219
      • Investigational Site Number 8400014

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR440340; 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; Pharmaceutical form: Solution for Injection, Route of administration: SC; Other Names: REGN3500; Drug: Fluticasone or Fluticasone/salmeterol combination; Pharmaceutical form: Aerosol, dry powder, Route of administration: Inhaled; Drug: Placebo for dupilumab; Pharmaceutical form: Solution for Injection, Route of administration: SC
Active Comparator: Dupilumab; Participants received 1 injection of dupilumab 300 mg along with 2 injections of SAR440340 placebo, SC Q2W for 12 weeks.	Drug: Fluticasone or Fluticasone/salmeterol combination; Pharmaceutical form: Aerosol, dry powder, Route of administration: Inhaled; Drug: Dupilumab; Pharmaceutical form: Solution for Injection, Route of administration: SC; Other Names: SAR231893 (REGN668); Drug: Placebo for SAR440340; Pharmaceutical form: Solution for Injection, Route of administration: SC
Experimental: SAR440340 + Dupilumab; Participants received 2 injections of SAR440340 300 mg along with 1 injection of dupilumab 300 mg, SC Q2W for 12 weeks.	Drug: SAR440340; Pharmaceutical form: Solution for Injection, Route of administration: SC; Other Names: REGN3500; Drug: Fluticasone or Fluticasone/salmeterol combination; Pharmaceutical form: Aerosol, dry powder, Route of administration: Inhaled; Drug: Dupilumab; Pharmaceutical form: Solution for Injection, Route of administration: SC; Other Names: SAR231893 (REGN668)
Placebo Comparator: Placebo; 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; Pharmaceutical form: Aerosol, dry powder, Route of administration: Inhaled; Drug: Placebo for dupilumab; Pharmaceutical form: Solution for Injection, Route of administration: SC; Drug: Placebo for SAR440340; Pharmaceutical form: Solution for Injection, Route of administration: SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 β2 adrenergic agonist (LABA) for at least 12 hours, and prior to administration of study drug.	Baseline, Week 12
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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2018
• Primary Completion (Actual): March 21, 2019
• Study Completion (Actual): August 7, 2019

Study Registration Dates

• First Submitted: December 15, 2017
• First Submitted That Met QC Criteria: December 22, 2017
• First Posted (Actual): January 2, 2018

Study Record Updates

• Last Update Posted (Actual): June 14, 2022
• Last Update Submitted That Met QC Criteria: May 25, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Sympathomimetics; Antibodies, Monoclonal; Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
• Other Study ID Numbers: ACT15102; 2017-003289-29 (EudraCT Number); U1111-1194-2185 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes