Dupilumab in CRSsNP

Overview

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

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: November 14, 2023

Detailed Description

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.

Interventions

  • Drug: Dupilumab SAR231893
    • Pharmaceutical form:Injection solution Route of administration: Subcutaneous
  • Drug: Placebo
    • Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Arms, Groups and Cohorts

  • Experimental: Part A and B: Dupilumab
    • Dupilumab administered every 2 weeks.
  • Placebo Comparator: Part A and B: Matching placebo
    • Placebo administered every 2 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Change from baseline to Week 24 in opacification of sinuses assessed by CT scan using the Lund Mackay (LMK) score in the dupilumab group only
    • Time Frame: Baseline to Week 24
    • LMK total score is based on assessment of the CT scan findings for each sinus area. The extent of opacification is rated between 0 (normal) to 24 (total opacification).

Secondary Measures

  • Change from baseline to Week 24 in opacification of sinuses assessed by CT scan using the LMK score
    • Time Frame: Baseline to Week 24
    • LMK total score is based on assessment of the CT scan findings for each sinus area. The extent of opacification is rated between 0 (normal) to 24 (total opacification).
  • Change from baseline to Week 24 in sTSS
    • Time Frame: Baseline to Week 24
    • The sTSS is a composite score derived from the following individual items: NC, anterior/posterior rhinorrhea, and facial pain/pressure. The total score ranges from 0-9. Higher scores on sTSS indicate greater overall symptom severity.
  • Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), and TEAEs leading to treatment discontinuation
    • Time Frame: Baseline to Week 64
    • Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), and TEAEs leading to treatment discontinuation.
  • Dupilumab concentration in serum
    • Time Frame: Baseline to Week 52
    • Dupilumab concentration in serum.
  • Incidence of treatment-emergent anti-drug antibodies (ADA) to dupilumab over time
    • Time Frame: Baseline to Week 64
    • Incidence of treatment-emergent anti-drug antibodies (ADA) to dupilumab over time.

Participating in This Clinical Trial

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:

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sanofi
  • Collaborator
    • Regeneron Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Clinical Sciences & Operations, Study Director, Sanofi

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