Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate to Severe COPD With Type 2 Inflammation (NOTUS)

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 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.
• Participants with current diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines, or documented history of asthma.
• 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.
• Long-term treatment with oxygen >4.0 L/min OR if a participant requires more than 2.0 L/min in order to maintain oxygen saturation >88%
• 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.