Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate-to-severe COPD With Type 2 Inflammation

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)

Approximately 68 weeks including a 4-week screening period, a 52-week treatment period, and 12 weeks of follow-up.

Eligibility Criteria:
Inclusion criteria:

* Participants with a physician diagnosis of COPD who met 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 were recorded by the investigator and defined as acute exacerbation of COPD (AECOPD) that required either systemic corticosteroids (intramuscular, intravenous, or oral) and/or antibiotics. One of the two required moderate exacerbations had to require the use of systemic corticosteroids. Severe exacerbations were 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 was 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 were 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 could be included).
* Diagnosis of α-1 anti-trypsin deficiency.

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