The Study of GR1802 in Patients With Chronic Rhinosinusitis With Nasal Polyps

Study Overview
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Brief Summary
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This is a multi-center, randomized, double blind, placebo-controlled study to evaluate the efficacy, safety, PK, PD and immumogenicity of GR1802 injection in comparison to placebo in addition to a background treatment of mometasone furcate nasal spray (MFNS) in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Patients will receive GR1802 injection or Placebo every 2 Weeks.

Detailed Description
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This is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial evaluating the preliminary efficacy and safety of GR1802 injection in patients with chronic rhinosinusitis with nasal polyps. The study consists of a Screening/run-in Period (up to 4 weeks), a Randomized, Double Blind Treatment Period (16 weeks) and a Safety Follow-up Period (8 weeks). 70 subjects will be randomized 1:1 into the 300 mg first dose doubling Q2W group and the placebo Q2W group. Throughout the dosing period, all subjects continued treatment with standard therapy at a stable dose. Patient-reported outcome including Nasal congestion score will be collected using patient diary. Central reading will be implemented to Nasal endoscopic nasal polyp score (NPS) and nasal polyp biopsy tissue analysis to eosinophil counts & percentage.

Official Title
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A Randomized, Double Blind, Placebo-Controlled Phase II Study to Evaluate the Efficacy, Safety of GR1802 Injection in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)

Conditions
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Chronic Rhinosinusitis With Nasal Polyps

Intervention / Treatment
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* Biological: GR1802 injection
* Biological: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bilateral CRSwNP with prior treatment with systemic corticosteroids (SCS), and/or contraindicate to or intolerance to SCS, and/or with prior surgery to nasal polyps Bilateral NPS of ≥5 with a minimum score of 2 in each nasal cavity at screening and at baseline. Ongoing symptoms of nasal congestion/obstruction(NCS score of 2 or 3 at screening and at baseline). Recorded use of intranasal corticosteroids for at least 4 weeks before screening Exclusion Criteria: Insufficient washout time for drugs that have an impact on the evaluation of efficacy and safety。 Concurrent disease that may interfere with the evaluation of safety and efficacy in subjects, or affect the risk- benefit evaluation of subjects. eg. specific ongoing nasal diseases, severe asthma, active infection, Severe cardiovascular disease, Severe laboratory test abnormalities. Other.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: GR1802<br>GR1802 injection 300mg every two weeks for 16-week treatment | Biological: GR1802 injection<br>* 150mg/1ml. 2 ml every two weeks Route of administration: Subcutaneous<br>|
| Placebo Comparator: Placebo Comparator: Placebo<br>Placebo every two weeks for 16-week treatment | Biological: placebo<br>* 0mg/1ml. 2 ml every two weeks Route of administration: Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at Week 16 in Nasal Congestion/Obstruction Symptom(NCS) Severity Score | Change from baseline in the NCS score. NCS score (0-3), higher score means worse nasal symptom. | at Week 16 | 
| Change From Baseline at Week 16 in Nasal Polyp Score | NPS score ranges from 0-8. (sum of 0-4 for each nasal passage scores), higher score means a worse outcome. | at Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the first response of NPS | Time to the first response of NPS (defined as bilateral endoscopic NPS improved ≥1). | Baseline up to Week 24 | 
| Lund-Mackay score | Change from baseline in the Lund-Mackay score on CT scan. The range of LM score is 0-24. Higher score means worse rhinosinusitis. | at Week 16 | 
| Bilateral endoscopic NPS | Change from baseline in the bilateral endoscopic NPS at Week 4, 8, 12, 24. | at Week 4, 8, 12, 24 | 
| Nasal Congestion/Obstruction Symptom score(NCS) | Change from baseline in NCS at Week 4, 8, 12, 24. | at Week 4, 8, 12, 24 | 
| University of Pennsylvania Smell Identification Test (UPSIT) | Change from baseline in UPSIT. UPSIT score (0-40). Higher score means better sense of smell. | at Week 16 | 
| Total Nasal Symptom Score(TNSS) score | Change from baseline in TNSS score. TNSS score (0-9). Higher score means worse nasal symptom. | at Week 16 | 
| Visual Analogue Scale (VAS) for Rhinosinusitis | Change from baseline in VAS score. VAS score (0-10). Higher score means worse nasal symptom. | at Week 16 | 
| Proportion of subjects receiving rescue therapy for nasal polyps | Rescue therapy includes Systemic Corticosteroids and endoscopic surgery | Baseline up to Week 24 | 
| Pharmacokinetics(PK) | Plasma concentration of GR1802 injection. PK parameter including trough concentration and exposure（CL/F, Vz/F etc.） | Baseline up to Week 24 | 
| Pharmacodynamics(PD) | Change from baseline in serum biomarker level (Periostin, TARC, total IgE and eosinophil level) and biomarkers in nasal secretions and nasal exfoliated cells。 | at Week 16 | 
| Anti-drug antibodies(ADA) | Incidence of ADA | Baseline up to Week 24 | 
| Safety parameters | Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), etc. | Baseline up to Week 24 |