Chronic Obstructive Pulmonary Disease MedDRA version: 26.1 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Sanofi-Aventis Recherche & Developpement
Eligibility
Sex/Gender
All
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 rhinosinusitis; 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 73 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
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 recurred - Former smokers (Parts A and B): Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit1, V1) or during the screening period For current smokers (PartB): vaping of any products (eg nicotine,THC) within 6 months prior to Screening (V1) 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 within 6 months before or at Screening (V1) 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 than 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 - Hypercapnia that requires bi-level positive airway pressure (BiPAP) - Moderate or severe exacerbation of COPD (AECOPD) within 8 weeks prior to Screening (V1) 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 (V1) or unstable angina within 6 months before Screening (V1) or during the screening period - Cardiac arrhythmias, including paroxysmal (eg, intermittent) atrial fibrillation Participants with isolated premature ventricular contractions (PVC) or premature atrial contractions (PAC) 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 mmHg or diastolic BP>110 mmHg 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 received Bacillus Calmette Guérin-vaccination within 12 weeks before Screening (V1) - History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening (V1) - Suspicion of, or confirmed, coronavirus disease 2019 (COVID19) infection or contact with known exposure to COVID19 at Screening (V1) or during the screening period; known history of COVID19 infection within 6 we
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: •Generate an airway gene expression signature for itepekimab treatment using Ribonucleic Acid (RNA) sequencing in former smokers with COPD Part B: •Validate the airway gene expression signature from Part A in former smokers with COPD in Part B;Secondary Objective: Part A: Evaluate in former smokers with COPD the •effect of itepekimab treatment on prespecified gene expression signatures •effect of itepekimab on blood eosinophil counts •safety and tolerability of itepekimab •immunogenicity to itepekimab in serum Part B: Evaluate in former smokers with COPD the: •effect of itepekimab on airway gene expression by RNA sequencing (pooled Part A and B) •effect of itepekimab on blood eosinophil counts Evaluate in current smokers with COPD the: •effect of itepekimab on airway gene expression by RNA sequencing Evaluate in former smokers and current smokers with COPD the: •differences in the effect of itepekimab on airway gene expression by RNA sequencing •differences in airway gene expression by RNA sequencing with COPD prior to treatment with itepekimab •effect of itepekimab treatment on prespecified gene expression signatures •safety and tolerability of itepekimab •immunogenicity to itepekimab in serum;Primary end point(s): 1 - Part A: Log2 relative change from baseline in gene expression in endobronchial biopsies at Week 12 ; As measured by RNA Sequencing, in former smokers with COPD 2 - Part B: Change from baseline in itepekimab treatment normalized enrichment score (NES) developed in Part A in endobronchial biopsies at Week 12 ; As measured by RNA Sequencing, in former smokers with COPD;Timepoint(s) of evaluation of this end point: 1, 2 - Baseline to Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A : 1 - Change from baseline in IL-33 treated eosinophil and mast cell-derived NES in endobronchial biopsies at Week 12 ; As measured by RNA Sequencing, in former smokers with COPD 2 - Change from baseline in preclinical mouse models-derived NES in endobronchial biopsies at Week 12 ; As measured by RNA Sequencing, in former smokers with COPD 3 - Change from baseline in bronchial allergen challenge-derived NES in endobronchial biopsies at Week 12 ; As measured by RNA Sequencing, in former smokers with COPD 4 - Change from baseline in blood eosinophil count at Week 12 ; In former smokers with COPD 5 - Incidence of treatment-emergent adverse events (TEAEs), adverse event of special interests (AESIs), serious adverse events (SAEs), and adverse events (AEs) leading to permanent treatment discontinuation ; In former smokers with COPD 6 - Incidence of potentially clinically significant abnormalities in clinical laboratory tests, vital signs and electrocardiogram (ECG) in the treatment-emergent period ; In former smokers with COPD 7 - Incidence of treatment-emergent anti-itepekimab antibody responses throughout the study ; In former smokers with COPD Part B : 8 - Log2 relative change from baseline in gene expression in endobronchial biopsies at Week 12 in former smokers with COPD (pooled Part A and B) ; As measured by RNA Sequencing, in former smokers with COPD (pooled Part A and B) 9 - Log2 relative change from baseline in gene expression in endobronchial biopsies at Week 12 in current smokers ; As measured by RNA Sequencing, in current smokers with COPD 10 - Log2 relative change from baseline in gene expression in endobronchial biopsies at Week 12 in former and current smokers with COPD ; As measured by RNA Sequencing, in former smokers and current smokers with COPD 11 - Gene expression in endobronchial biopsies at Baseline ; As measured by RNA Sequencing, in former smokers and current smokers with COPD 12 - Change from baseline in IL-33 trea | — |
Countries
Belgium, Denmark, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactEsther Beeks
Sanofi-Aventis Recherche & Développement
Outcome results
None listed