Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD)

Inclusion criteria :

• Participant must be 40 to 85 years of age inclusive.

• Physician diagnosis of COPD for at least 1 year (based on Global Initiative forChronic Obstructive Lung Disease [GOLD] definition).

• Smoking history of ≥10 pack-years:

• For former smokers: participants who report that they are not currently smokingand smoking cessation must have occurred ≥6 months prior to Screening (Visit 1A) with an intention to quit permanently.

• For current smokers: participants who report that they are currently smokingtobacco (participant smoked at least 1 cigarette per day on average during thepast 7 days) at Screening (Visit 1A) and who are not currently participating inor planning to initiate a smoking cessation intervention at Screening (Visit 1A) or during Screening period.

• Participants with moderate-to-severe COPD

• Participant-reported history of signs and symptoms of chronic bronchitis (chronicproductive cough for at least 3 months in the year prior to Screening in aparticipant in whom other causes of chronic cough [eg, inadequately treatedgastroesophageal reflux or chronic rhinosinusitis; or clinical diagnosis ofbronchiectasis] has been excluded).

• Documented history of high exacerbation risk defined as having had ≥2 moderate or ≥1severe exacerbations within the year prior to Screening (Visit 1A), with at least 1exacerbation treated with systemic corticosteroids. At least one exacerbation musthave occurred while participants were on their current controller therapy:

• Moderate exacerbations will be recorded by the Investigator and are defined asacute worsening of respiratory symptoms that requires either systemiccorticosteroids (IM, IV, or oral) and/or antibiotics.

• Severe exacerbations will be recorded by the Investigator and are defined asAECOPD that require hospitalization or observation for >24 hours in emergencydepartment/urgent care facility.

• Participants with standard of care controller therapy, for ≥3 months prior toScreening (Visit 1A) and at a stable dose of controller therapy for at least 1 monthprior to the Screening, including either: inhaled corticosteroid (ICS) + long-actingbeta-agonist (LABA), long-acting muscarinic antagonist (LAMA) + LABA or LAMA + LABA

• ICS.

• Body mass index (BMI) ≥18.0 kg/m^2, or BMI ≥16.0 kg/m^2 for participants enrolled inEast-Asian countries.

• Female participant is not pregnant, not breastfeeding, and at least one of thefollowing 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 of asthma according to the Global Initiative for Asthma (GINA)guidelines, or documented history of asthma unless asthma resolved before 18 yearsof age and has not recurred.

• For former smokers: Active smoking or vaping of any products (eg, nicotine,tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit 1A).

• For current smokers: vaping of any products (eg, nicotine, THC) within 6 monthsprior to Screening (Visit 1A).

• Clinically significant new abnormal electrocardiogram (ECG) within 6 months priorto, or at Screening (Visit 1A) that may affect the participant's participation inthe study.

• Clinically significant and current pulmonary disease other than COPD, eg,sarcoidosis, interstitial lung disease, bronchiectasis (clinical diagnosis),diagnosis of α-1 anti-trypsin deficiency, or another diagnosed pulmonary disease.

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

• Hypercapnia requiring bilevel positive airway pressure (BiPAP).

• Moderate or severe exacerbation of COPD (AECOPD) within 4 weeks prior to Screening (Visit 1A).

• Prior history of / planned: lung pneumonectomy for any reason, or lung volumereduction procedures (including bronchoscopic volume reduction) for COPD. Note:Surgical biopsy, or segmentectomy, or wedge resection, or lobectomy for otherdiseases would not be excluded.

• Unstable ischemic heart disease, including acute myocardial infarction within thepast 1 year prior to Screening, or unstable angina in the 6 months prior toScreening (Visit 1A).

• Cardiac arrhythmias including paroxysmal (eg, intermittent) atrial fibrillation.

• Uncontrolled hypertension (ie, systolic blood pressure [BP] >180 mm Hg or diastolicBP >110 mm Hg with or without use of anti-hypertensive 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 prior toScreening (Visit 1A).

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

• Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection or incontact with known exposure to COVID-19 at Screening (Visit 1A); known history ofCOVID-19 infection within 4 weeks prior to Screening (Visit 1A); history ofrequiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO)secondary to COVID-19 within 3 months prior to Screening (Visit 1A); participantswho have had a COVID-19 infection prior Screening (Visit 1A) who have not yetsufficiently recovered to participate in the procedures of a clinical trial.

• Evidence of acute or chronic infection requiring systemic treatment withantibacterial, antiviral, antifungal, antiparasitic, or antiprotozoal medicationswithin 4 weeks before Screening (Visit 1A), significant viral infections within 4weeks before Screening (Visit 1A) that may not have been treated with antiviraltreatment (eg, influenza receiving only symptomatic treatment).

• Participants with active autoimmune disease or participants using immunosuppressivetherapy for autoimmune disease (eg, rheumatoid arthritis, inflammatory boweldisease, primary biliary cirrhosis, systemic lupus erythematosus, multiplesclerosis.

• History of malignancy within 5 years before Screening (Visit 1A), except completelytreated in situ carcinoma of the cervix, completely treated and resolvednonmetastatic squamous or basal cell carcinoma of the skin.

• 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.