Evaluation of SAR440340 and as Combination Therapy With Dupilumab in Moderate-to-Severe Asthma Participants
Condition: Asthma
MeSH terms: Asthma
Intervention: SAR440340; Dupilumab; Fluticasone or Fluticasone/salmeterol combination; Placebo for SAR440340; Placebo for dupilumab
Intervention description: Pharmaceutical form: Solution for Injection, Route of administration: SC; Pharmaceutical form: Solution for Injection, Route of administration: SC; Pharmaceutical form: Aerosol, dry powder, Route of administration: Inhaled; Pharmaceutical form: Solution for Injection, Route of administration: SC; Pharmaceutical form: Solution for Injection, Route of administration: SC
Intervention MeSH terms: Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 296.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

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.
    

Eligibility 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.