Chronic bronchitis Chronic Obstructive Pulmonary Disease COPD
Conditions
Interventions
- Compound: itepekimab
- Pharmaceutical form: pre-filled syringes with 2ml solution for injection (150
mg/ml)
- Route of administration: subcutaneous
Sponsors
Sanofi BV
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Participant must be 40 to 70 years of age inclusive - Physician diagnosis of COPD for at least 1 year (based on the Global Initiative for Chronic Obstructive Lung Disease [GOLD] definition). - Smoking history of >=10 pack-years -- For former smokers: Participants who report that they are not currently smoking, and smoking cessation must have occurred >=6 months prior to Screening (Visit 1) with an intention to quit permanently. -- For current smokers (not eligible for Part A): Participants who report that they are currently smoking tobacco (participant smoked at least 5 cigarettes per day on average during the past 7 days) at Screening (Visit 1) and at Baseline, and who are not currently participating in, or planning to initiate, a smoking cessation intervention at Screening (Visit 1) or during the screening period. - Participant-reported history of signs and symptoms of chronic bronchitis (chronic productive cough for at least 3 months in the year before screening in a participant in whom other causes of chronic cough [eg, inadequately treated gastroesophageal reflux or chronic rhinosinustis; or clinical diagnosis of bronchiectasis] have been excluded). - Documented or self-reported history of exacerbation having had >=1 moderate or severe exacerbation within the 5 years prior to Screening (Visit 1), with at least 1 exacerbation treated with systemic corticosteroids: -- Moderate exacerbations are defined as an acute worsening of respiratory symptoms that requires either systemic corticosteroids (intramuscular [IM], intravenous [IV], or oral) and/or antibiotics. -- Severe exacerbations are defined as AECOPD that require hospitalization or observation for >24 hours in emergency department/urgent care facility. - Participants treated with SoC controller therapy for >=3 months before Screening (Visit 1) and at a stable dose and regimen of controller therapy for at least 1 month before the screening visit AND during the screening period, including either: triple therapy with LAMA + LABA + ICS or double therapy with ICS + LABA or LABA + LAMA or ICS + LAMA, or monotherapy with LABA or LAMA. - Participants who have received appropriate vaccination according to local recommendations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), administered a minimum of 1 week prior to Screening (Visit 1). - Body mass index (BMI) >=18 kg/m2 - A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: -- Not a women of child-bearing potential (WOCBP) or -- A WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 20 weeks after the last dose of study intervention.
Exclusion criteria
Exclusion criteria: - Current diagnosis or previously confirmed diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines unless asthma resolved before 18 years of age and has not returned. - For former smokers (Parts A and B): Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit 1) or during the screening period. For current smokers (Part B): vaping of any products (eg, nicotine, THC) within 6 months prior to Screening (Visit 1) or during the screening period. - Participants who are expected to be regularly exposed to environmental (ie, "second hand") tobacco smoke in an indoor setting during the screening or treatment periods (former smokers only) - Clinically significant new abnormal electrocardiogram (ECG) within 6 months before or at Screening (Visit 1) that may affect the participant*s participation in the study. - Clinically significant and current pulmonary disease other than COPD, eg, sarcoidosis, interstitial lung disease, bronchiectasis (clinical diagnosis), diagnosis of a-1 anti-trypsin deficiency, or another diagnosed pulmonary disease. - Diagnosis of cor pulmonale, evidence of right cardiac failure, or moderate-to-severe pulmonary hypertension. - Participants who require more that 2L/min of long-term treatment with oxygen at rest. Participants who use up to 4L/min of supplemental oxygen during exercise may enroll. Oxygen during sleep is allowed. - Participants who receive long-term treatment with oxygen or a low oxygen saturation on room air at rest. - Hypercapnia that requires bi-level positive airway pressure (BiPAP). - Moderate or severe exacerbation of COPD (AECOPD) within 8 weeks prior to Screening (Visit 1) or during the screening period. - Prior history of pneumonectomy, lobectomy, segmentectomy, or therapeutic bronchoscopy procedure (including bronchoscopic volume reduction). Note: Prior history of surgical lung biopsy or wedge resection are not exclusion criteria. - Any surgery or major procedures (including those requiring conscious sedation) planned to occur during the study. Minor skin procedures are allowed. - Unstable ischemic heart disease, including acute myocardial infarction within 1 year before Screening (Visit 1), or unstable angina within 6 months before Screening (Visit 1) or during the screening period. - Cardiac arrhythmias, including paroxysmal (eg, intermittent) atrial fibrillation. Participants with isolated premature ventricular contractions (PVCs) or premature atrial contractions (PACs) may be considered for inclusion. - Cardiomyopathy, as defined by Stage III-IV (New York Heart Association) cardiac failure, or other relevant cardiovascular disorder that that may affect the participant*s participation in the study. - Any underlying disease requiring the use of prophylaxis for endocarditis. - Uncontrolled hypertension (ie, systolic blood pressure [BP] >180 mm Hg or diastolic BP >110 mm Hg with or without use of antihypertensive therapy). - Participants with active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection (TBI), or who are at high risk of contracting TB (such as close contact with individuals with active or latent TB) or r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Log2 relative change from baseline in gene expression in endobronchial biopsies at Week 12 Part B: Change from baseline in itepekimab treatment normalized enrichment score (NES) developed in Part A in endobronchial biopsies at Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A: - Change from baseline in IL-33 treated eosinophil and mast cell-derived NES in endobronchial biopsies at Week 12 - Change from baseline in preclinical mouse models derived NES in endobronchial biopsies at Week 12 - Change from baseline in bronchial allergen challenge derived NES in endobronchial biopsies at Week 12 - Change from baseline in blood eosinophil count at Week 12 - Incidence of TEAEs, AESIs, SAEs, and AEs leading to permanent treatment discontinuation - Incidence of potentially clinically significant abnormalities in clinical laboratory tests, vital signs and ECG abnormalities in the treatment-emergent period - Incidence of treatment-emergent anti-itepekimab antibody responses throughout the study Part B: - Log2 relative change from baseline in gene expression in endobronchial biopsies at Week 12 - Log2 relative change from baseline in gene expression in endobronchial biopsies at Week 12 - Log2 relative change from baseline in gene expression in endobronchial biopsies at Week 12 - Gene expression in endobronchial biopsies at Week 0 (Baseline) - Change from baseline in IL-33 treated eosinophil and mast cell-derived NES in endobronchial biopsies at Week 12 - Change from baseline in preclinical mouse models derived NES in endobronchial biopsies at Week 12 - Change from baseline in bronchial allergen challenge derived NES in endobronchial biopsies at Week 12 - Change from baseline in blood eosinophil count at Week 12 - Incidence of TEAEs, AESIs, SAEs, and AEs leading to permanent treatment discontinuation - Incidence of potentially clinically significant laboratory tests, vital signs, and ECG abnormalities in the treatment-emergent period - Incidence of treatment-emergent anti-itepekimab antibody responses throughout the study | — |
Countries
Netherlands
Outcome results
None listed