A Study of CM310 in Patients With Chronic Rhinosinusitis With Nasal Polyposis （CROWNS-2）

Study Overview
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Brief Summary
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This is a multi-center, randomized, double blind, placebo-controlled Phase III study to evaluate the efficacy and safety of CM310, and to observe the life quality of subjects, the Pharmacokinetics, Pharmacodynamics and immumogenicity of CM310 in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP).

Detailed Description
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The study consists of a Screening Period (up to 4 weeks), Treatment Period (24 weeks for double-blind treatment period and 28 weeks for open-label maintenance treatment) and Safety Follow-up Period (8 weeks). 180 patients who meet eligibility criteria will be randomized 1:1 to receive either CM310 300 mg or matched placebo subcutaneously every two weeks (Q2W) for a total of 12 times at the double-blind treatment period and 14 times at the open-label treatment period. All patients will receive MFNS on a daily basis as a background treatment throughout the study. Central reading will be implemented to nasal endoscopic nasal polyp score (NPS) , CT scans to Lund-Mackay score and volume of the involved area of nasosinusitis on 3D-construction images, and nasal polyp biopsy tissue analysis to eosinophil counts & percentage.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of CM310 in Patients With Chronic Rhinosinusitis With Nasal Polyposis

Conditions
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Chronic Rhinosinusitis With Nasal Polyposis

Intervention / Treatment
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* Biological: CM310
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: with chronic rhinosinusitis with nasal polyposis (CRSwNP). Nasal Polyp Score (NPS) of ≥5 with a minimum score of 2 in each nasal cavity. NCS score of 2 or 3 at screening period, and at least 2 at baseline. Contraception. Exclusion Criteria: Not enough washingout period for previous therapy, e.g., less than 10 weeks or 5 half-lives (whichever is longer) for IL-4Rα antagonists, less than 8 weeks or 5 half-lives for biologic therapy/systemic immunosuppressant, less than 6 months for sinus surgery (including polypectomy). Participated and any studies of CM310. With malignant or benign tumor of nasal cavity. Vaccination with live attenuated vaccine within 12 weeks before randomization or during the planned study period.

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: CM310<br>CM310 300mg is given subcutaneously (SC) every two weeks | Biological: Placebo<br>* once every two weeks<br>|
| Placebo Comparator: Placebo<br>Placebo is given subcutaneously (SC) every two weeks | Biological: CM310<br>* 300 mg every two weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nasal Polyps Score (NPS) | Change from baseline in the Nasal Polyps Score (NPS) at week 24. NPS score ranges from 0-8 (sum of 0-4 for each nasal passage scores), higher score means a worse outcome. | at week 24 | 
| Nasal Congestion Score (NCS) | Change from baseline in the Nasal Congestion Score (NCS) at week 24. NCS score range from 0 to 3, with higher score means worse nasal symptom. | at week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety parameters | Incidence of treatment-emergent adverse events (TEAEs). | Baseline up to Week 60 | 
| Pharmacokinetics (PK) | Concentration of CM310 in serum | Baseline up to Week 60 | 
| Pharmacodynamics (PD) | Change from baseline in serum biomarker level (Thymus- and activation-regulated chemokine). | Baseline up to Week 60 | 
| Anti-drug antibodies (ADA) | Incidence of ADA. | Baseline up to Week 60 |