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

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ClinicalTrials.gov Identifier: NCT03387852
Recruitment Status : Completed
First Posted : January 2, 2018
Last Update Posted : September 13, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE December 15, 2017
First Posted Date  ICMJE January 2, 2018
Last Update Posted Date September 13, 2019
Actual Study Start Date  ICMJE March 12, 2018
Actual Primary Completion Date August 7, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2017)
Loss of asthma control (LOAC) events [ Time Frame: Baseline to Week 12 ]
Proportion of patients with LOAC
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03387852 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2017)
Change in forced expiratory volume in 1 second (FEV1) [ Time Frame: Baseline to Week 12 ]
FEV1 change from baseline at Week 12 (pre- and post-bronchodilator)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of SAR440340 and as Combination Therapy With Dupilumab in Moderate-to-Severe Asthma Patients
Official Title  ICMJE 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
Brief Summary

Primary Objective:

To evaluate the effects of SAR440340/REGN3500 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/REGN3500 and dupilumab, compared with placebo, on forced expiratory volume in 1 second (FEV1).

To evaluate the effects of coadministration of SAR440340/REGN3500 and dupilumab, compared with SAR440340 and compared with dupilumab, on FEV1.

To assess safety and tolerability of SAR440340/REGN3500 alone and in coadministration with dupilumab.

Detailed Description The total duration of the study (per patient) is approximately 36 weeks, including 4 weeks screening, 12 weeks treatment, and 20 weeks post-treatment.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: SAR440340/REGN3500
    Pharmaceutical form:Solution for Injection Route of administration: Subcutaneous
  • Drug: Dupilumab
    Pharmaceutical form:Solution for Injection Route of administration: Subcutaneous
    Other Name: SAR231893 (REGN668)
  • Drug: Fluticasone or Fluticasone/salmeterol combination
    Pharmaceutical form:Aerosol, dry powder Route of administration: Inhaled
  • Drug: Placebo for SAR440340 (REGN3500)
    Pharmaceutical form:Solution for Injection Route of administration: Subcutaneous
  • Drug: Placebo for dupilumab
    Pharmaceutical form:Solution for Injection Route of administration: Subcutaneous
Study Arms  ICMJE
  • Experimental: SAR440340/REGN3500 Monotherapy
    SAR440340/REGN3500 administered by subcutaneous (SC) injections every 2 weeks for 12 weeks and coadministration of dupilumab placebo by SC injection every 2 weeks for 12 weeks
    Interventions:
    • Drug: SAR440340/REGN3500
    • Drug: Fluticasone or Fluticasone/salmeterol combination
    • Drug: Placebo for dupilumab
  • Dupilumab Monotherapy
    Dupilumab administered by SC injection every 2 weeks for 12 weeks and coadministration of SAR440340/REGN3500 placebo by SC injections every 2 weeks for 12 weeks
    Interventions:
    • Drug: Dupilumab
    • Drug: Fluticasone or Fluticasone/salmeterol combination
    • Drug: Placebo for SAR440340 (REGN3500)
  • Experimental: SAR440340/REGN3500 and Dupilumab Coadministration
    SAR440340/REGN3500 administered by SC injections every 2 weeks for 12 weeks and coadministration of dupilumab administered by SC injection every 2 weeks for 12 weeks
    Interventions:
    • Drug: SAR440340/REGN3500
    • Drug: Dupilumab
    • Drug: Fluticasone or Fluticasone/salmeterol combination
  • Placebo Comparator: Placebo
    Coadministration of matching placebos for SAR440340/REGN3500 and dupilumab administered by SC injections, respectively, every 2 weeks for 12 weeks
    Interventions:
    • Drug: Fluticasone or Fluticasone/salmeterol combination
    • Drug: Placebo for SAR440340 (REGN3500)
    • Drug: Placebo for dupilumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 12, 2019)
297
Original Estimated Enrollment  ICMJE
 (submitted: December 22, 2017)
240
Actual Study Completion Date  ICMJE August 7, 2019
Actual Primary Completion Date August 7, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

  • Adult patients with a physician diagnosis of asthma for at least 12 months based on the Global Initiative for Asthma (GINA) 2017 Guidelines.
  • Patients with existing treatment with medium to high dose ICS (≥250 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.
  • Patients with prebronchodilator forced expiratory volume (FEV1) >40% of predicted normal at Visit 1/Screening. Pre-bronchodilator FEV1 ≥50% but ≤85% of predicted normal at Visit 2/Baseline.
  • Patients with reversibility of at least 12% and 200 mL in FEV1 after administration of 2 to 4 puffs (200-400 mcg) 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 <8mg/mL) within 12 months prior to Visit 1/Screening is considered acceptable to meet this inclusion criterion.
  • Patients must have 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:

  • Patients <18 years or >70 years of age (i.e., have reached the age of 71 at the screening visit).
  • Patients with body mass index (BMI) <16.
  • Chronic lung disease (for example, chronic obstructive pulmonary disease [COPD], or idiopathic pulmonary fibrosis [IPF]), which may impair lung function.
  • History of life threatening asthma (i.e., severe exacerbation that requires intubation).
  • Co-morbid disease that might interfere with the evaluation of investigational medicinal product (IMP).
  • Patients 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 V2/randomization. During the screening period, an ACQ-5 of up to ≤4 is acceptable.
  • Anti-immunoglobulin E (IgE) therapy (e.g., omalizumab [Xolair®]) within 130 days prior to Visit 1 or any other biologic therapy (including anti-IL5 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 is longer.
  • Patients with a history of a systemic hypersensitivity reaction to a biologic drug.
  • Patients 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 patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Chile,   Russian Federation,   Argentina,   Mexico,   Poland,   Turkey,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03387852
Other Study ID Numbers  ICMJE ACT15102
2017-003289-29 ( EudraCT Number )
U1111-1194-2185 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP