Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03387852
Recruitment Status : Completed
First Posted : January 2, 2018
Results First Posted : March 29, 2022
Last Update Posted : June 14, 2022
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
Asthma Drug: SAR440340 Drug: Dupilumab Drug: Fluticasone or Fluticasone/salmeterol combination Drug: Placebo for SAR440340 Drug: Placebo for dupilumab Phase 2

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 296 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 12, 2018
Actual Primary Completion Date : March 21, 2019
Actual Study Completion Date : August 7, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Dupilumab

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: 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: Dupilumab
Pharmaceutical form: Solution for Injection, Route of administration: SC
Other Name: SAR231893 (REGN668)

Drug: Fluticasone or Fluticasone/salmeterol combination
Pharmaceutical form: Aerosol, dry powder, Route of administration: Inhaled

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 Name: REGN3500

Drug: Dupilumab
Pharmaceutical form: Solution for Injection, Route of administration: SC
Other Name: SAR231893 (REGN668)

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

Drug: Placebo for dupilumab
Pharmaceutical form: Solution for Injection, Route of administration: SC


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Percentage of Participants With Loss of Asthma Control [ Time Frame: From Baseline up to Week 12 ]
    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.


Secondary Outcome Measures :
  1. Change From Baseline at Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline, Week 12 ]
    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.

  2. Change From Baseline at Week 12 in Post-bronchodilator Forced Expiratory Volume in 1 Second [ Time Frame: Baseline, Week 12 ]
    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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03387852


Locations
Show Show 71 study locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] September 6, 2018
Statistical Analysis Plan  [PDF] November 28, 2018

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03387852    
Other Study ID Numbers: ACT15102
2017-003289-29 ( EudraCT Number )
U1111-1194-2185 ( Other Identifier: UTN )
First Posted: January 2, 2018    Key Record Dates
Results First Posted: March 29, 2022
Last Update Posted: June 14, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Xhance
Salmeterol Xinafoate
Fluticasone-Salmeterol Drug Combination
Antibodies, Monoclonal
Anti-Inflammatory Agents
 Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors