Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of SAR440340 (Anti-IL-33 mAb) in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: SAR440340; Placebo; Any Inhaled Corticosteroids as prescribed by treating physician as standard of care; Any Long Acting Beta Agonist as prescribed by treating physician as standard of care; Any Long Acting Muscarinic Agonist as prescribed by treating physician as standard of care; Any short-acting β agonist as prescribed by treating physician as standard of care
Intervention description: Pharmaceutical form: Solution for injection; Route of administration: SC; Pharmaceutical form: Solution for injection; Route of administration: SC; Pharmaceutical form: Aerosol or Dry Powder inhaler Route of administration: Inhaled; Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: Inhaled; Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: Inhaled; Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: inhaled
Intervention MeSH terms: Cholinergic Agents; Muscarinic Agonists
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 343.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To investigate effects of SAR440340 (anti-interleukin-33 [IL-33] monoclonal antibody [mAb])
      compared with placebo, on the annualized rate of moderate-to-severe acute exacerbations of
      COPD (AECOPD) over up to 52 weeks of treatment.

        -  Moderate exacerbations were recorded by the Investigator and defined as AECOPD that
           require either systemic corticosteroids (such as intramuscular, intravenous or oral)
           and/or antibiotics.

        -  Severe exacerbations were recorded by the Investigator and defined as AECOPD requiring
           hospitalization, emergency medical care visit or resulting in death.

      Secondary Objectives:

      To investigate effects of SAR440340 compared with placebo, on improving respiratory function,
      as assessed by pre-bronchodilator forced exploratory volume in 1 second (FEV1).

      To evaluate effects of SAR440340 compared with placebo, on post-bronchodilator FEV1.

      To evaluate effects of SAR440340 compared with placebo, on duration from baseline to first
      moderate or severe AECOPD event.

      To evaluate effects of SAR440340 compared with placebo, on safety and tolerability.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with a diagnosis of chronic obstructive pulmonary disease (COPD) for at
             least 1 year (based on Global Initiative for Chronic Obstructive Lung Disease [GOLD]
             definition).

          -  Participants with moderate-to-severe COPD (post-bronchodilator forced expiratory
             volume in 1 second [FEV1]/forced vital capacity [FVC] less than [<] 70 percent (%) and
             post-bronchodilator FEV1% predicted <80%, but greater than equal to [>=] 30%).

          -  Participants with COPD assessment test (CAT) score >=10 at Screening.

          -  Participants with reported history of signs and symptoms of chronic bronchitis
             (chronic productive cough for 3 months in the year up to screening in a participant in
             whom other causes of chronic cough [e.g., gastroesophageal reflux, chronic
             rhinosinusitis, bronchiectasis] had been excluded).

          -  Participants with a documented history (e.g., medical record verification) of >=2
             moderate exacerbations or >=1 severe exacerbation within the year prior to screening.
             A moderate exacerbation was defined as an acute exacerbation of COPD (AECOPD)
             requiring systemic corticosteroids (oral, intravenous, or intramuscular) and/or
             treatment with antibiotics (however, use of antibiotics alone does not qualify as a
             "moderate exacerbation" unless documentation was available that use of antibiotics was
             necessary for treatment of worsening symptoms of COPD). A severe exacerbation was
             defined as an AECOPD that required a hospitalization.

          -  Participants with standard of care background therapy, for 3 months and at a stable
             dose for at least 1 month, including either:

          -  Double therapy: Long acting beta agonist (LABA) + Long acting muscarinic agonist
             (LAMA) or inhaled corticosteroid (ICS) + LABA or ICS + LAMA.

        or

          -  Triple therapy: LABA + LAMA + ICS.

          -  Current or former smokers with a smoking history of >=10 packs/year.

        Exclusion criteria:

          -  Concomitant severe diseases or diseases for which the use of ICS (e.g., active
             pulmonary tuberculosis, etc.) or LABA were contraindicated (e.g., diagnosis of a
             history of significant cardiovascular diseases, insulin-dependent diabetes mellitus,
             hyperthyroidism, thyrotoxicosis, pheochromocytoma, hypokalemia).

          -  Use of injectable glucocorticosteroids or oral systemic glucocorticosteroids within
             previous 1 month or more than 4 courses of intravenous glucocorticosteroids within the
             previous 6 months.

          -  Participants with bronchial thermoplasty procedure (up to 3 years prior to Visit 1).

          -  A current diagnosis of asthma according to the Global Initiative for Asthma (GINA)
             guidelines.

          -  Significant pulmonary disease other than COPD (e.g., lung fibrosis, sarcoidosis,
             interstitial lung disease, pulmonary hypertension, bronchiectasis, eosinophilic
             granulomatosis with polyangiitis, significant sleep apnea on Bilevel Positive Airway
             Pressure, etc.) or another diagnosed pulmonary or systemic disease associated with
             elevated peripheral eosinophil counts.

          -  Diagnosis of α-1 anti-trypsin deficiency.

          -  Advanced COPD with need for chronic (greater than [>] 15 hours/day) oxygen support.

          -  Participant with a moderate or severe acute exacerbation of COPD event within previous
             4 weeks.

          -  A participant who has experienced an upper or lower respiratory tract infection within
             previous 4 weeks.

          -  Prior history of or planned pneumonectomy or lung volume reduction surgery.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.