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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 : Recruiting
First Posted : January 2, 2018
Last Update Posted : December 10, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

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.


Condition or disease Intervention/treatment Phase
Asthma Drug: SAR440340/REGN3500 Drug: Dupilumab Drug: Fluticasone or Fluticasone/salmeterol combination Drug: Placebo for SAR440340 (REGN3500) Drug: Placebo for dupilumab Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 240 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
Estimated Primary Completion Date : April 9, 2019
Estimated Study Completion Date : August 27, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Dupilumab

Arm Intervention/treatment
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
Drug: SAR440340/REGN3500
Pharmaceutical form:Solution for Injection Route of administration: Subcutaneous

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: Subcutaneous

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
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

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
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

Placebo Comparator: Placebo
Coadministration of matching placebos for SAR440340/REGN3500 and dupilumab administered by SC injections, respectively, every 2 weeks for 12 weeks
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




Primary Outcome Measures :
  1. Loss of asthma control (LOAC) events [ Time Frame: Baseline to Week 12 ]
    Proportion of patients with LOAC


Secondary Outcome Measures :
  1. 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)



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.


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 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.


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


Contacts
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-Us@sanofi.com

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Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03387852     History of Changes
Other Study ID Numbers: ACT15102
2017-003289-29 ( EudraCT Number )
U1111-1194-2185 ( Other Identifier: UTN )
First Posted: January 2, 2018    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Salmeterol Xinafoate
Fluticasone Propionate, Salmeterol Xinafoate 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
Glucocorticoids