Dupilumab in CRSsNP

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Uncontrolled, Chronic Rhinosinusitis Without Nasal Polyposis (CRSsNP)

Primary Objective:

To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on computerized tomography (CT) scan in the dupilumab group only

Secondary Objectives:

• To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on CT scan and sinus total symptom score (sTSS) compared to placebo
• To evaluate the safety and tolerability of dupilumab in CRSsNP patients compared to placebo
• To evaluate the pharmacokinetics (PK) of dupilumab in CRSsNP patients compared to placebo
• Assessment of immunogenicity to dupilumab over time compared to placebo

The duration of study for each participant will include 2-4 weeks of screening period, 24-52 weeks randomized investigational medicinal product (IMP) intervention period and 12 weeks of follow-up period.

Inclusion Criteria:

• Participant must be at least 18 years of age at the time of signing the informed consent form (ICF).

• Participants must have bilateral inflammation of paranasal sinuses in CT scan with LMK ≥8 and bilateral ethmoid opacification before randomization.

• Participants must have ongoing symptoms of loss of smell and rhinorrhea (anterior/posterior) of any severity, with or without facial pain/pressure for at least 12 consecutive weeks by Visit 1.

• Participants must have ongoing symptoms of nasal congestion (NC)/obstruction at least 12 consecutive weeks before Visit 1 and a NC score of ≥ 2 at Visit 1 (day score) and Visit 2 (weekly average score).

• Participants must have sTSS (NC, rhinorrhea, facial pain/pressure) ≥5 at Visit 1 (day score) and Visit 2 (weekly average score).

• Participants must have one of the 2 following features:

  • Prior sinonasal surgery (see note at end of section 5.2 for definitions of sinonasal surgery) for CRS,
  • Treatment with systemic corticosteroids (SCS) therapy for CRS as defined by any dose and duration within the prior 2 years before screening (Visit 1) or intolerance/contraindication to SCS.

Exclusion Criteria:

• Participants with nasal conditions/concomitant nasal diseases such as nasal polyposis in endoscopy at Visit 1 or with history of nasal polyposis etc., making them non-evaluable at Visit 1 or for the primary efficacy

• Nasal cavity malignant tumor and benign tumors.

• Forced expiratory volume (FEV1) ≤50% of predicted normal at Visit 1.

• Radiologic suspicion or confirmed invasive or expansive fungal rhinosinusitis.

• Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect participation in the study

• Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.

• Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection

• Known or suspected immunodeficiency

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

• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit 1 or during the screening period.

• History of systemic hypersensitivity or anaphylaxis to dupilumab or any of its excipients.

• Participants in prior dupilumab clinical trial or have been treated with commercially available dupilumab within 12 months or who discontinued dupilumab use due to adverse event.

• Participants who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as Xhance™, during screening period.

• Participants on unstable dose of intranasal corticosteroids (INCS) spray 4 weeks prior to Screening Visit (Visit1) and during screening period.

• Participants who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit 1.

• Participants who have taken:

  • Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to Visit 1
  • Any investigational mAb within 5 half-lives prior to Visit 1
  • Anti-IgE therapy (omalizumab) within 4 months prior to Visit 1.

• Treatment with a live (attenuated) vaccine within 4 weeks prior to Visit 1

• Leukotriene antagonists/modifiers unless participant is on a continuous treatment for at least 30 days prior to Visit 1.

• Initiation of allergen immunotherapy within 3 months prior to Visit 1 or a plan to begin therapy or change its dose during the screening or treatment period.

• Participants received SCS during screening period (between Visit 1 and Visit 2).

• Either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to Screening Visit (Visit 1).

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