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

Brief description of study

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 or 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 antidrug antibodies (ADA)

Detailed description of study

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

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Chronic Obstructive Pulmonary Disease
  • Age: Between 40 Years - 85 Years
  • Gender: Male or Female

Inclusion Criteria:

Inclusion criteria:

  • Participants with a physician diagnosis of COPD who meet the following criteria at
    • 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:

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.

Updated on 21 Dec 2022 . Study ID: NCT04456673

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