Chronic Obstructive Pulmonary Disease
Conditions
Interventions
Dupilumab arm:
Drug: Dupilumab (Genetical Recombination) (SAR231893)
Pharmaceutical form: Solution for injection, Route of administration: Subcutaneous
Drug: Inhaled Corticosteroid - Background thera
Sponsors
Sanofi K.K.
Eligibility
Sex/Gender
All
Inclusion 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 30% and =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
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 alpha-1 anti-trypsin deficiency.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Annual rate of acute COPD exacerbation (AECOPD) [Time Frame: Baseline to week 52] Annualized rate of moderate or severe COPD exacerbations over the 52-week treatment period compared to placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change in pre-bronchodilator FEV1 [Time Frame: Baseline to week 12] Change in pre-bronchodilator FEV1 from baseline to Week 12 compared to placebo 2. Change in SGRQ [Time Frame: Baseline to week 52] Change from baseline to Week 52 in SGRQ total score compared to placebo 3. Improvement in SGRQ [Time Frame: Baseline to week 52] Proportion of patients with SGRQ improvement >=4 points at Week 52 4. 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 5. 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 6. 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 7. 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 8. 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 9. 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 10. Adverse events [Time Frame: Baseline through week 64] Number of adverse events (AEs)/treatment-emergent adverse events (TEAEs) 11. Potentially clinically significant abnormality (PCSA) in laboratory tests [Time Frame: Baseline through week 64] Percentage of patients with at least one incidence of PCSA 12. Anti-drug antibodies [Time Frame: Baseline to week 64] Incidence of anti-drug antibodies against dupilumab | — |
Countries
Argentina, Bulgaria, Canada, Chile, China, Czechia, Denmark, Finland, Germany, Hungary, Israel, Italy, Japan, Mexico, Poland, Republic of Korea, Romania, Russian Federation, Slovakia, Spain, Sweden, Turkey, Ukraine, United States
Contacts
Public ContactUnit Clinical
Sanofi K.K.
Outcome results
None listed