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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CM310 | Experimental | CM310 300mg is given subcutaneously (SC) every two weeks |
|
| Placebo | Placebo Comparator | Placebo is given subcutaneously (SC) every two weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CM310 | Biological | 300 mg every two weeks |
| |
| Placebo |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Luo Zhang | Beijing Tong-Ren hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Tongren Hospital, CMU | Beijing | Beijing Municipality | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40824573 | Derived | Shen S, Yan B, Wang M, Wu D, Piao Y, Tang J, Yang X, Cao Z, Xue J, Liu W, Liu S, Shi L, Wang G, Song X, Lu Y, Chen J, Jiang L, Ye J, Yu S, Yang Y, Fang H, Li J, Shi H, Fan J, Yan H, Wang H, Chen B, Wang C, Zhang L; CROWNS-2 Study Investigators. Stapokibart for Severe Uncontrolled Chronic Rhinosinusitis With Nasal Polyps: The CROWNS-2 Randomized Clinical Trial. JAMA. 2025 Aug 18;334(11):962-72. doi: 10.1001/jama.2025.12515. Online ahead of print. | |
| 39220573 |
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| Biological |
once every two weeks |
|
| 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 |
| Derived |
| Shen S, Yan B, Wang M, Wu D, Wang C, Zhang L. Anti-IL-4Ralpha monoclonal antibody (CM310) in patients with chronic rhinosinusitis with nasal polyps (CROWNS-2): Rationale and design of a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Asia Pac Allergy. 2024 Aug;14(3):118-123. doi: 10.5415/apallergy.0000000000000156. Epub 2024 Aug 5. |