Resumen

Objetivo primario: Evaluar la eficacia de dupilumab administrado cada 2 semanas en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) de moderada o grave, medida por: * Tasa anualizada de exacerbaciones agudas moderadas o graves de la EPOC (AECOPD) Objetivos secundarios: Evaluar el efecto de dupilumab administrado cada 2 semanas sobre: * Volumen espiratorio forzado en el primer segundo (FEV1) prebroncodilatador durante 12 semanas en comparación con placebo. * Calidad de vida relacionada con la salud, evaluada por el cambio desde el inicio hasta la Semana 52 en el Cuestionario Respiratorio de St. George (SGRQ). * FEV1 prebroncodilatador durante 52 semanas en comparación con placebo. * Evaluaciones de la función pulmonar. * Exacerbaciones moderadas y graves de la EPOC. * Evaluar la seguridad y tolerabilidad. * Evaluar la exposición sistémica a dupilumab y la incidencia de anticuerpos antifármaco (ADA).

Descripción detallada

Aproximadamente 68 semanas, incluyendo un período de selección de 4 semanas, un período de tratamiento de 52 semanas y 12 semanas de seguimiento.

Elegibilidad

Edad mínima: 40 YearsEdad máxima: 85 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 participant 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 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 is contraindicated.
Evidence of Type 2 inflammation: Participants 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. Participants who were participating in the acute phase of a pulmonary rehabilitation program, ie, who started rehabilitation \<4 weeks prior to screening (Note: participants 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.

Criterios de exclusión

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.

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 : 0320007

Berazategui, Buenos Aires, Argentina

Investigational Site Number : 0320006

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320004

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320001

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320003

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320010

La Plata, Buenos Aires, Argentina

Investigational Site Number : 0320013

Lobos, Buenos Aires, Argentina

Investigational Site Number : 0320005

Quilmes, Buenos Aires F.D., Argentina

Investigational Site Number : 0320011

Córdoba, Córdoba Province, Argentina

Investigational Site Number : 0320008

Rosario, Santa Fe Province, Argentina

Investigational Site Number : 0320009

Rosario, Santa Fe Province, Argentina

Investigational Site Number : 0320002

Buenos Aires, Argentina

Investigational Site Number : 0320012

Launs Este, Argentina

Estudio pivotal aleatorizado, doble ciego, controlado con placebo, de grupos paralelos, de 52 semanas para evaluar la eficacia, seguridad y tolerabilidad de dupilumab en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) de moderada a grave con inflamación de tipo 2

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 : 0320007

Investigational Site Number : 0320006

Investigational Site Number : 0320004

Investigational Site Number : 0320001

Investigational Site Number : 0320003

Investigational Site Number : 0320010

Investigational Site Number : 0320013

Investigational Site Number : 0320005

Investigational Site Number : 0320011

Investigational Site Number : 0320008

Investigational Site Number : 0320009

Investigational Site Number : 0320002

Investigational Site Number : 0320012

Patrocinadores