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

• Status: Recruiting
• Trial end date: 2023-05-22
• Target enrollment: 0
• Participant gender: All

Summary

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)

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Treatments: Antibodies, Monoclonal; Cholinergic Agents; Muscarinic Agonists; Muscarinic Antagonists

Criteria

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.