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

Sanofi

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Placebo for SAR440340; Drug: SAR440340; Drug: Dupilumab; Drug: Fluticasone or Fluticasone/salmeterol combination; Drug: Placebo for dupilumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03387852

U1111-1194-2185 (Other Identifier)

2017-003289-29 (EudraCT Number)

ACT15102

Details and patient eligibility

About

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.

Full 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.

Enrollment: 296 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

296 participants in 4 patient groups, including a placebo group

SAR440340

Experimental group

Description:

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.

Treatment:

Drug: Placebo for dupilumab

Drug: Fluticasone or Fluticasone/salmeterol combination

Drug: SAR440340

Dupilumab

Active Comparator group

Description:

Participants received 1 injection of dupilumab 300 mg along with 2 injections of SAR440340 placebo, SC Q2W for 12 weeks.

Treatment:

Drug: Fluticasone or Fluticasone/salmeterol combination

Drug: Placebo for SAR440340

Drug: Dupilumab

SAR440340 + Dupilumab

Experimental group

Description:

Participants received 2 injections of SAR440340 300 mg along with 1 injection of dupilumab 300 mg, SC Q2W for 12 weeks.

Treatment:

Drug: Fluticasone or Fluticasone/salmeterol combination

Drug: Dupilumab

Drug: SAR440340

Placebo

Placebo Comparator group

Description:

Participants received 2 SC injections of SAR440340 placebo along with 1 SC injection of dupilumab placebo Q2W for 12 weeks.

Treatment:

Drug: Placebo for dupilumab

Drug: Fluticasone or Fluticasone/salmeterol combination

Drug: Placebo for SAR440340