Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD

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 forChronic Obstructive Lung Disease [GOLD] definition).

• Smoking history of ≥10 pack-years

• For former smokers: Participants who report that they are not currentlysmoking, 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 thatthey are currently smoking tobacco (participant smoked at least 5 cigarettesper day on average during the past 7 days) at Screening (Visit 1) and atBaseline, and who are not currently participating in, or planning to initiate,a smoking cessation intervention at Screening (Visit 1) or during the screeningperiod.

• Participant-reported history of signs and symptoms of chronic bronchitis (chronicproductive cough for at least 3 months in the year before screening in a participantin whom other causes of chronic cough [eg, inadequately treated gastroesophagealreflux or chronic rhinosinusitis; or clinical diagnosis of bronchiectasis] have beenexcluded).

• Documented or self-reported history of exacerbation having had ≥1 moderate or severeexacerbation within the 5 years prior to Screening (Visit 1), with at least 1exacerbation treated with systemic corticosteroids:

• Moderate exacerbations are defined as an acute worsening of respiratorysymptoms that requires either systemic corticosteroids (intramuscular [IM],intravenous [IV], or oral) and/or antibiotics.

• Severe exacerbations are defined as AECOPD that require hospitalization orobservation 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 1month 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 localrecommendations 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, notbreastfeeding, 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 interventionperiod and for at least 20 weeks after the last dose of study intervention.

Exclusion Criteria:

• Current diagnosis or previously confirmed diagnosis of asthma according to theGlobal Initiative for Asthma (GINA) guidelines unless asthma resolved before 18years of age and has not recurred.

• For former smokers (Parts A): 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 thescreening period.

• Participants who are expected to be regularly exposed to environmental (ie, 'secondhand') tobacco smoke in an indoor setting during the screening or treatment periods (former smokers only).

• Clinically significant new abnormal electrocardiogram (ECG) within 6 months beforeor at Screening (Visit 1) that may affect the participant's participation in thestudy.

• Clinically significant and current pulmonary disease other than COPD, eg,sarcoidosis, interstitial lung disease, bronchiectasis (clinical diagnosis),diagnosis of α1 anti-trypsin deficiency, or another diagnosed pulmonary disease.

• Diagnosis of cor pulmonale, evidence of right cardiac failure, or moderate-to-severepulmonary hypertension.

• Participants who require more than 2 L/min of long-term treatment with oxygen atrest. Participants who use up to 4L/min of supplemental oxygen during exercise mayenroll. 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 (Visit 1) or during the screening period.

• Prior history of pneumonectomy, lobectomy, segmentectomy, or therapeuticbronchoscopy procedure (including bronchoscopic volume reduction). Note: Priorhistory 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 yearbefore 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 prematureatrial contractions (PACs) may be considered for inclusion.

• Cardiomyopathy, as defined by Stage III-IV (New York Heart Association) cardiacfailure, or other relevant cardiovascular disorder that that may affect theparticipant'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 diastolicBP >110 mm Hg with or without use of antihypertensive therapy).

• Participants with active tuberculosis (TB), latent TB, a history of incompletelytreated TB, suspected extrapulmonary TB infection (TBI), or who are at high risk ofcontracting TB (such as close contact with individuals with active or latent TB) orreceived Bacillus Calmette Guérin (BCG)-vaccination within 12 weeks before Screening (Visit 1).

• History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serologyat Screening (Visit 1).

• Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection or contactwith known exposure to COVID19 at Screening (Visit 1) or during the screeningperiod; known history of COVID19 infection within 6 weeks before Screening (Visit 1); history of requiring mechanical ventilation or extracorporeal membraneoxygenation (ECMO) secondary to COVID-19 within 12 months before Screening (Visit 1); participants who have had a COVID-19 infection before Screening (Visit 1) whohave not yet sufficiently recovered to participate in the procedures of a clinicaltrial.

• Evidence of acute or chronic infection requiring systemic treatment withantibacterial, antiviral, antifungal, antiparasitic, or antiprotozoal medicationswithin 6 weeks before Screening (Visit 1) or during the screening period,significant viral infections within 6 weeks before Screening (Visit 1) or during thescreening period that may not have been treated with antiviral treatment (eg,influenza receiving only symptomatic treatment).

• Participants with active autoimmune disease or participants taking immunosuppressivetherapy for autoimmune disease (eg, rheumato arthritis, inflammatory bowel disease,primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis).

• History of malignancy within 5 years before Screening (Visit 1), or during thescreening period, except completely treated in situ carcinoma of the cervix,completely treated and resolved nonmetastatic squamous or basal cell carcinoma ofthe skin.

• Symptomatic herpes zoster within 3 months prior to screening.

• Previous use of Itepekimab.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.