Randomized, double-blind, placebo-controlled, parallel-group Phase 3 study to evaluate the efficacy, safety, and tolerability of SAR440340/REGN3500/itepekimab (anti-IL-33 mAb) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD)

- Participant must be 40 to 85 years of age inclusive.
- Physician diagnosis of COPD for at least 1 year (based on 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 1A)
with an
intention to quit permanently.
-- For current smokers: participants who report that they are currently smoking
tobacco
(participant smoked at least 1 cigarette per day on average during the past 7
days) at
Screening (Visit 1A) and who are not currently participating in or 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
(chronic
productive cough for at least 3 months in the year prior to Screening in a
participant in
whom other causes of chronic cough [eg, inadequately treated gastroesophageal
reflux or
chronic rhinosinusitis; or clinical diagnosis of bronchiectasis] has been
excluded).
- Documented history of high exacerbation risk defined as having had >=2
moderate or >=1
severe exacerbations within the year prior to Screening (Visit 1A), with at
least 1
exacerbation treated with systemic corticosteroids. At least one exacerbation
must have
occurred while participants were on their current controller therapy:
-- Moderate exacerbations will be recorded by the Investigator and are defined
as acute
worsening of respiratory symptoms that requires either systemic corticosteroids
(IM, IV, or
oral) and/or antibiotics.
-- Severe exacerbations will be recorded by the Investigator and are defined as
AECOPD
that require hospitalization or observation for >24 hours in emergency
department/urgent
care facility.
- Participants with standard of care controller therapy, for >=3 months prior to
Screening
(Visit 1A) and at a stable dose of controller therapy for at least 1 month
prior to the
Screening, including either: inhaled corticosteroid (ICS) + long-acting
beta-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/m2 for participants
enrolled in
East-Asian countries.
- Female participant 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.

- Current diagnosis of asthma according to the Global Initiative for Asthma
(GINA)
guidelines, or documented history of asthma unless asthma resolved before 18
years of
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 months
prior to
Screening (Visit 1A).
- Clinically significant new abnormal electrocardiogram (ECG) within 6 months
prior to, or
at Screening (Visit 1A) 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
α-1 anti-trypsin
deficiency, or another diagnosed pulmonary disease.
- Diagnosis of cor pulmonale, evidence of right cardiac failure, or
moderate-to-severe
pulmonary 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 volume
reduction
procedures (including bronchoscopic volume reduction) for COPD. Note: Surgical
biopsy,
or segmentectomy, or wedge resection, or lobectomy for other diseases would not
be
excluded.
- Unstable ischemic heart disease, including acute myocardial infarction within
the past 1
year prior to Screening, or unstable angina in the 6 months prior to Screening
(Visit 1A).
- Cardiac arrhythmias including paroxysmal (eg, intermittent) atrial
fibrillation.
- Uncontrolled hypertension (ie, systolic blood pressure [BP] >180 mm Hg or
diastolic BP
>110 mm Hg with or without use of anti-hypertensive 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 (BCG)-vaccination within 12 weeks prior to Screening (Visit 1A).
- History of human immunodeficiency virus (HIV) infection or positive HIV 1/2
serology at
Screening (Visit 1A).
- Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection or
in contact
with known exposure to COVID-19 at Screening (Visit 1A); known history of
COVID-19
infection within 4 weeks prior to Screening (Visit 1A); history of requiring
mechanical
ventilation or extracorporeal membrane oxygenation (ECMO) secondary to COVID-19
within 3 months prior to Screening (Visit 1A); participants who have had a
COVID-19
infection prior Screening (Visit 1A) who have not yet sufficiently recovered to
participate in
the procedures of a clinical trial.
- Evidence of acute or chronic infection requiring systemic treatment with anti
bacterial,
antiviral, antifungal, antiparasitic, or antiprotozoal medications within 4
weeks before
Screening (Visit 1A), significant viral infections within 4 weeks before
Screening (Visit 1A)
that may not have been treated with antiviral treatment (eg, influenza
receiving only
symptomatic treatment).
- Participants with active autoimmune disease or participants using
immunosuppressive
therapy for autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel
disease,
primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis.
- History of malignancy within 5 years before Screening (Visit 1A), except
completely
treated in situ carcinoma of the cervix, completely treated and resolved
nonmetastatic
squamous or basal cell carcinoma of the skin.
- Previous use of itepekimab.