Resumen

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)

Descripción detallada

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

Elegibilidad

Edad mínima: 40 YearsEdad máxima: 80 YearsSexo: ALL

Criterios de inclusión

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.
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.

Criterios de exclusión

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.

Intervenciones

drug

Dupilumab SAR231893

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

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

Ubicaciones

Investigational Site Number :0320011

CABA, Buenos Aires, Argentina

Investigational Site Number :0320002

CABA, Buenos Aires, Argentina

Investigational Site Number :0320003

CABA, Buenos Aires, Argentina

Investigational Site Number :0320004

CABA, Buenos Aires, Argentina

Investigational Site Number :0320012

La Plata, Buenos Aires, Argentina

Investigational Site Number :0320007

Quilmes, Buenos Aires F.D., Argentina

Investigational Site Number :0320006

Rosario, Santa Fe Province, Argentina

Investigational Site Number :0320009

San Miguel de Tucumán, Tucumán Province, Argentina

Investigational Site Number :0320001

Buenos Aires, Argentina

Investigational Site Number :0320005

Buenos Aires, Argentina

Investigational Site Number :0320008

Mar del Plata, Argentina

Investigational Site Number :0320010

Mendoza, Argentina

A Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) With Type 2 Inflammation

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Dupilumab SAR231893

Inhaled Corticosteroid

Inhaled Long-Acting Beta Agonist

Inhaled Long-Acting Muscarinic Antagonist

Placebo

Ubicaciones

Investigational Site Number :0320011

Investigational Site Number :0320002

Investigational Site Number :0320003

Investigational Site Number :0320004

Investigational Site Number :0320012

Investigational Site Number :0320007

Investigational Site Number :0320006

Investigational Site Number :0320009

Investigational Site Number :0320001

Investigational Site Number :0320005

Investigational Site Number :0320008

Investigational Site Number :0320010

Patrocinadores