• Change in pre-bronchodilator FEV1 [ Time Frame: Baseline to Week 12 ]
  Change in pre-bronchodilator FEV1 from baseline to Week 12 compared to placebo
• Change in SGRQ [ Time Frame: Baseline to Week 52 ]
  Change from baseline to Week 52 in SGRQ total score compared to placebo
• Improvement in SGRQ [ Time Frame: Baseline to Week 52 ]
  Proportion of patients with SGRQ improvement ≥4 points at Week 52
• Change in pre-bronchodilator FEV1 from baseline to Week 52 [ Time Frame: Baseline to Week 52 ]
  Change in pre-bronchodilator FEV1 from baseline to Week 52 compared to placebo
• Change in pre-bronchodilator FEV1 from baseline to time points up to Week 44 [ Time Frame: Baseline to Weeks 2, 4, 8, 24, 36, 44 ]
  Change in pre-bronchodilator FEV1 from baseline to weeks other than 12 and 52 (i.e. Weeks 2, 4, 8, 24, 36, and 44) compared to placebo
• Change in post-bronchodilator FEV1 lung function [ Time Frame: Baseline to Weeks 2, 4, 8, 12, 24, 36, 52 ]
  Change in post-bronchodilator FEV1 from baseline at Weeks 2, 4, 8, 12, 24, 36 and 52 compared to placebo
• Change in forced expiratory flow (FEF) 25-75% [ Time Frame: Baseline to Weeks 2, 4, 8, 12, 24, 36, 44, 52 ]
  Change in FEF 25-75% from baseline to Weeks 2, 4, 8, 12, 24, 36, 44 and 52
• Annualized rate of severe AECOPD [ Time Frame: Baseline through Week 52 ]
  Annualized rate of severe COPD exacerbations compared to placebo over the 52-week treatment period
• Time to first AECOPD [ Time Frame: Baseline through Week 52 ]
  Time to first moderate or severe COPD exacerbation compared with placebo during the 52-week treatment period
• Adverse events [ Time Frame: Baseline through Week 64 ]
  Number of adverse events (AEs)/treatment-emergent adverse events (TEAEs)
• Potentially clinically significant abnormality (PCSA) in laboratory tests [ Time Frame: Baseline through Week 64 ]
  Percentage of patients with at least one incidence of PCSA
• Anti-drug antibodies [ Time Frame: Baseline to Week 64 ]
  Incidence of anti-drug antibodies against dupilumab

• Change in pre-bronchodilator FEV1 [ Time Frame: Baseline to Week 12 ]
  Change in pre-bronchodilator FEV1 from baseline to Week 12 compared to placebo
• Change in SGRQ [ Time Frame: Baseline to Week 52 ]
  Change from baseline to Week 52 in SGRQ total score compared to placebo
• Improvement in SGRQ [ Time Frame: Baseline to Week 52 ]
  Proportion of patients with SGRQ improvement ≥4 points at Week 52
• Change in pre-bronchodilator FEV1 from baseline to Week 52 [ Time Frame: Baseline to Week 52 ]
  Change in pre-bronchodilator FEV1 from baseline to Week 52 compared to placebo
• Change in pre-bronchodilator FEV1 from baseline to time points up to Week 48 [ Time Frame: Baseline to Weeks 2, 4, 8, 16, 20, 24, 28, 36, 44, 48 ]
  Change in pre-bronchodilator FEV1 from baseline to weeks other than 12 and 52 (i.e. Weeks 2, 4, 8, 16, 20, 24, 28, 36, 44 and 48) compared to placebo
• Change in post-bronchodilator FEV1 lung function [ Time Frame: Baseline to Weeks 2, 4, 8, 12, 24, 36, 52 ]
  Change in post-bronchodilator FEV1 from baseline at Weeks 2, 4, 8, 12, 24, 36 and 52 compared to placebo
• Change in forced expiratory flow (FEF) 25-75% [ Time Frame: Baseline to Weeks 2, 4, 8, 12, 16, 24, 28, 36, 44, 52 ]
  Change in FEF 25-75% from baseline to Weeks 2, 4, 8, 12, 16, 24, 28, 36, 44 and 52
• Annualized rate of severe AECOPD [ Time Frame: Baseline through Week 52 ]
  Annualized rate of severe COPD exacerbations compared to placebo over the 52-week treatment period
• Time to first AECOPD [ Time Frame: Baseline through Week 52 ]
  Time to first moderate or severe COPD exacerbation compared with placebo during the 52-week treatment period
• Adverse events [ Time Frame: Baseline through Week 64 ]
  Number of adverse events (AEs)/treatment-emergent adverse events (TEAEs)
• Potentially clinically significant abnormality (PCSA) in laboratory tests [ Time Frame: Baseline through Week 64 ]
  Percentage of patients with at least one incidence of PCSA
• Anti-drug antibodies [ Time Frame: Baseline to Week 64 ]
  Incidence of anti-drug antibodies against dupilumab

Primary Objective:

To evaluate the efficacy of dupilumab administered every 2 weeks in patients with moderate-or severe Chronic Obstructive Pulmonary Disease (COPD) as measured by

• Annualized rate of acute moderate and severe COPD exacerbation (AECOPD)

Secondary Objectives:

To evaluate the effect of dupilumab administered every 2 weeks on

• Pre-bronchodilator forced expiratory volume in 1 second (FEV1) over 12 weeks compared to placebo
• Health related quality of life, assessed by the change from baseline to Week 52 in the St. George's Respiratory Questionnaire (SGRQ)
• Pre-bronchodilator FEV1 over 52 weeks compared to placebo
• Lung function assessments
• Moderate and severe COPD exacerbations
• To evaluate safety and tolerability
• To evaluate dupilumab systemic exposure and incidence of anti-drug antibodies (ADA)

• Drug: Dupilumab SAR231893

  Pharmaceutical form: Solution for injection

  Route of administration: Subcutaneous

  Other Name: Dupixent
• Drug: Inhaled Corticosteroid

  Pharmaceutical form: Inhaled Powder

  Route of administration: Oral inhalation

• Drug: Inhaled Long-Acting Beta Agonist

  Pharmaceutical form: Inhaled Powder

  Route of administration: Oral inhalation

• Drug: Inhaled Long-Acting Muscarinic Antagonist

  Pharmaceutical form: Inhaled Powder

  Route of administration: Oral inhalation

• Drug: Placebo

  Pharmaceutical form: Solution for injection

  Route of administration: Subcutaneous

• Experimental: Dupilumab
  Dupilumab administered every 2 weeks
  Interventions:

  • Drug: Dupilumab SAR231893
  • Drug: Inhaled Corticosteroid
  • Drug: Inhaled Long-Acting Beta Agonist
  • Drug: Inhaled Long-Acting Muscarinic Antagonist
• Placebo Comparator: Placebo
  Placebo dose administered every 2 weeks
  Interventions:

  • Drug: Inhaled Corticosteroid
  • Drug: Inhaled Long-Acting Beta Agonist
  • Drug: Inhaled Long-Acting Muscarinic Antagonist
  • Drug: Placebo

Inclusion criteria:

• Participants with a physician diagnosis of COPD who meet the following criteria at screening:

  • Current or former smokers with a smoking history of ≥10 pack-years.
  • Moderate-to-severe COPD (post-bronchodilator FEV1/ forced vital capacity [FVC] ratio <0.70 and post-bronchodilator FEV1 % predicted >30% and ≤70%).
  • Medical Research Council (MRC) Dyspnea Scale grade ≥2.
  • Patient-reported history of signs and symptoms of chronic bronchitis (chronic productive cough) for 3 months in the year up to screening in the absence of other known causes of chronic cough.
  • Documented history of high exacerbation risk defined as exacerbation history of ≥2 moderate or ≥1 severe within the year prior to inclusion. At least one exacerbation should have occurred while the patient was taking inhaled corticosteroid (ICS)/long acting beta agonist (LABA)/long acting muscarinic antagonist (LAMA) (or LABA/LAMA if ICS is contraindicated). Moderate exacerbations are recorded by the investigator and defined as acute exacerbation of COPD (AECOPD) that require either systemic corticosteroids (intramuscular, intravenous, or oral) and/or antibiotics. One of the two required moderate exacerbations has to require the use of systemic corticosteroids. Severe exacerbations are recorded by the investigator and defined as AECOPD requiring hospitalization or observation >24 hours in emergency department/urgent care facility.
  • Background triple therapy (ICS + LABA + LAMA) for 3 months prior to randomization with a stable dose of medication for ≥1 month prior to Visit 1; Double therapy (LABA + LAMA) allowed if ICS is contraindicated.
• Evidence of Type 2 inflammation: Patients with blood eosinophils ≥300 cells/microliter at Visit 1.

Exclusion criteria:

• COPD diagnosis for less than 12 months prior to randomization.
• A current diagnosis of asthma or history of asthma according to the 2018 Global Initiative for Asthma (GINA) guidelines or other accepted guidelines.
• Significant pulmonary disease other than COPD (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome etc) or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
• Cor pulmonale, evidence of right cardiac failure.
• Treatment with oxygen of more than 12 hours per day.
• Hypercapnia requiring Bi-level ventilation.
• AECOPD as defined in inclusion criteria within 4 weeks prior to screening, or during the screening period.
• Respiratory tract infection within 4 weeks prior to screening, or during the screening period.
• History of, or planned pneumonectomy or lung volume reduction surgery. Patients who are participating in the acute phase of a pulmonary rehabilitation program, ie, who started rehabilitation <4 weeks prior to screening (Note: patients in the maintenance phase of a rehabilitation program can be included).
• Diagnosis of α-1 anti-trypsin deficiency.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.