Study Assessing the Long-term Effect of Dupilumab on Prevention of Lung Function Decline in Adult Patients With Uncontrolled Moderate to Severe Asthma

Inclusion Criteria:

• Participant must be at least 18 (or the legal age of consent in the jurisdiction inwhich the study is taking place) years of age inclusive, at the time of signing theinformed consent.

• Patients with a physician diagnosis of asthma (according to Global Initiative forAsthma (GINA) 2021) for ≥12 months

• Treatment with medium to high dose inhaled corticosteroids (ICS) in combination witha second controller (eg, long-acting beta-2 adrenergic receptor agonists (LABA),leukotriene receptor antagonists (LTRA) with a stable dose ≥1 month prior to Visit

1. Patients requiring a third controller for their asthma will be consideredeligible for this study, and it should also be on stable dose ≥1 month prior toVisit 1. Patients requiring an additional controller as a fourth controller (Montelukast) for another type 2 comorbid condition such as allergic rhinitis willbe considered eligible for this study, and should be on a stable dose for ≥1 monthprior to Visit 1.

• Pre-bronchodilator forced expiratory volume (FEV1) ≤ 80% of predicted normal foradults at Visits 1 and 2, prior to randomization

• Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at Visits 1 and 2, prior to randomization.

• Variable airflow obstruction as documented by one or more of the following (at least 1 needs to be met): i) Positive reversibility test: ≥12% and 200 mL improvement in FEV1 after SABAadministration prior to randomization, or documented in the 24 months prior to Visit

1. OR, ii) Positive bronchial challenge test: fall in FEV1 of ≥20% with standarddoses of methacholine, or ≥15% with standardized hyperventilation, hypertonic salineor mannitol challenge prior to randomization or documented in the 24 months prior toVisit 1 OR, iii) Average daily diurnal Peak flow variability of >10% over a 2-weekperiod, documented in the past 24 months prior to Screening Visit 1. OR, iv) Airflowvariability in clinic FEV1 >12% and 200 mL between visits outside of respiratoryinfections, documented in the past 24 months prior to Screening Visit 1. OR v) FEV1increases by more than 12% and 200mL from baseline after 4 weeks ofanti-inflammatory treatment.

• Reversibility test: Three attempts may be made during the Screening Period until theBaseline visit to meet the qualifying criteria for reversibility. This is onlyrequired if reversibility or other evidence of expiratory airflow limitationeligibility criteria was not performed within 24 months prior to Visit 1.

• FeNO ≥35 ppb at Visit 2, prior to randomization.

• History of ≥1 severe exacerbation(s) in the previous year before Visit1 defined as adeterioration of asthma requiring: i) Use of systemic corticosteroids for ≥3 days; or ii) Hospitalization or emergencyroom visit because of asthma, requiring systemic corticosteroids.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• History or clinical evidence of chronic obstructive pulmonary disease (COPD)including Asthma-COPD Overlap Syndrome (ACOS) or any other significant lung disease (eg, emphysema, lung fibrosis, sarcoidosis, interstitial lung disease, pulmonaryhypertension, bronchiectasis, Churg-Strauss Syndrome).

• Severe asthma exacerbation requiring treatment with systemic corticosteroid (SCS) inthe past month before visit 1 or during the screening period.

• Current acute bronchospasm or status asthmaticus.

• Diagnosed pulmonary (other than asthma) or systemic disease associated with elevatedperipheral eosinophil counts.

• Severe concomitant illness(es) that, in the Investigator's judgment, would adverselyaffect the participant's participation in the study. Examples include, but are notlimited to, participants with short life expectancy, uncontrolled diabetes,cardiovascular conditions, severe renal conditions (eg, participants on dialysis),or other severe endocrinological, gastrointestinal, metabolic, pulmonary,psychiatric, or lymphatic diseases. The specific justification for participantsexcluded under this criterion will be noted in the study documents (chart notes,case report forms [CRFs], etc).

• Patients with active tuberculosis (TB) or non-tuberculous mycobacterial infection,or a history of incompletely treated TB will be excluded from the study unless it iswell documented by a specialist that the participant has been adequately treated andcan now start treatment with a biologic agent, in the medical judgment of theInvestigator and/or infectious disease specialist. Tuberculosis testing will beperformed on a country by country basis, according to local guidelines if requiredby regulatory authorities or ethics boards, or if TB is suspected by theinvestigator

• Known or suspected immunodeficiency, including history of invasive opportunisticinfections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, andaspergillosis) despite infection resolution, or otherwise recurrent infections ofabnormal frequency or prolonged duration suggesting an immune-compromised status, asjudged by the Investigator.

• Active malignancy or history of malignancy within 5 years before Visit 1 (screeningvisit), except completely treated in situ carcinoma of the cervix and completelytreated and resolved non metastatic squamous or basal cell carcinoma of the skin.

• Active chronic or acute infection requiring treatment with systemic antibiotics,antivirals, antifungals or receiving only symptomatic treatment (e.g. influenza orCOVID-19) within 2 weeks before the screening visit (Visit 1) or during thescreening period.

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

• Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or useof antiparasitic drugs within 2 weeks before Visit 1 (screening visit) or during thescreening and run-in period

• Current smoker (cigarette or e-cigarette) or cessation of smoking within 6 monthsprior to Visit 1.

• Previous smoker with a smoking history >10 pack-years.

• History of systemic hypersensitivity or anaphylaxis to dupilumab or any otherbiologic therapy, including any excipient.

• Any biologic therapy (including experimental treatments and dupilumab) or any otherbiologic therapy/immunosuppressant/immunomodulators within 4 weeks prior to V1 or 5half-lives, whichever is longer.

• Treatment with a live (attenuated) vaccine within 4 weeks before Visit 1 (screeningvisit) or during the screening period.

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