Dupilumab in Japanese Patients With Chronic Rhinosinusitis With Nasal Polyp (SINUS-M52)

Study Overview
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Brief Summary
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This is a Phase 4, open-label, single-arm, multicenter study to evaluate the efficacy and safety of dupilumab subcutaneous (SC) injection monotherapy in Japanese participants aged 18 or older with CRSwNP that is not adequately controlled with existing therapies. Duration of study period (per participant): Screening Period (2 to 4 weeks) Intervention Period (up to 52 weeks±3 days)

Official Title
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A Single-arm, 52 Weeks, Phase 4 Study to Assess the Efficacy and Safety of Dupilumab in Patients With Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP) Who Are Not Adequately Controlled With Existing Therapies

Conditions
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Chronic Rhinosinusitis With Nasal Polyps

Intervention / Treatment
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* Drug: Dupilumab SAR231893


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants ≧18 years of age. Participants with bilateral sinonasal polyposis that despite prior treatment with systemic corticosteroids (SCS) anytime within the past 2 years; and/or had a medical contraindication / intolerance to SCS; and/or had prior surgery for NP at the screening visit, had: An endoscopic bilateral NPS of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity). Ongoing symptoms (for at least 8 weeks prior to Visit [V] 1) of nasal congestion/blockage/obstruction with moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity of greater than 1 at the time of enrollment (V2), and loss of smell, rhinorrhea (anterior/posterior). Participant's body weight > 30 kg at V1. Signed written informed consent. Exclusion Criteria: Participant with conditions/concomitant diseases making them non evaluable at V1 or for the primary efficacy endpoint such as: Antrochoanal polyps; Nasal septal deviation that would occlude at least one nostril; Acute sinusitis, nasal infection or upper respiratory infection; Ongoing rhinitis medicamentosa; Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis; Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis; Participant with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil, etc). Participant diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before V1 or during screening Undergone any and/or sinus intranasal surgery within 6 months before V1. Participant who had participated in prior dupilumab clinical study or had been treated with commercially available dupilumab The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dupilumab<br>Dupilumab every 2 weeks (q2w). Dosing interval may be changed from q2w to q4w at week 24 | Drug: Dupilumab SAR231893<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous (SC)<br>* Other names: REGN668;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with nasal polyp score (NPS) improvement from baseline ≥1 at Week 24 | NPS is the sum of the right and left nostrils, ranging from 0 (no polyps) to 8 (large polyps causing complete obstruction). | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 24 in bilateral NPS | NPS is the sum of the right and left nostrils, ranging from 0 (no polyps) to 8 (large polyps causing complete obstruction). | Baseline to Week 24 | 
| Change from baseline to Week 24 in in nasal congestion/obstruction (NC) symptom severity score using the CRSwNP nasal symptom diary | The nasal congestion/obstruction scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms'). | Baseline to Week 24 | 
| Change from baseline to Week 24 in opacification of sinuses assessed by computerized tomography (CT) scan using the Lund Mackay (LMK) score | 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). | Baseline to Week 24 | 
| Change from baseline to Week 24 in total symptom score (TSS) | The total symptom score (TSS) is a composite score (ranging between 0 and 9) consisting of the sum of the following symptoms assessed daily in the morning: nasal congestion/obstruction, decreased/loss of sense of smell, rhinorrhea (average of anterior/posterior nasal discharge). | Baseline to Week 24 | 
| Change from baseline to Week 24 in loss of smell symptom severity score using the nasal symptom diary | The loss of sense of smell symptom severity scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms') | Baseline to Week 24 | 
| Change from baseline to Week 24 in visual analogue scale (VAS) for rhinosinusitis | The VAS for rhinosinusitis ranges from 0 to 10 cm. Mild = VAS 0-3; Moderate = VAS >3 to 7; Severe = VAS >7 to 10. | Baseline to Week 24 | 
| Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and TEAEs leading to treatment discontinuation | Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and TEAEs leading to treatment discontinuation. | Baseline to Week 52 |