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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 CM310 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).
The study consists of a Screening/run-in Period (up to 4 weeks), a Randomized, Double Blind Treatment Period (16 weeks, till End-of-Treatment Visit) and a Safety Follow-up Period (8 weeks, till End-of-Study Visit).
56 patients who meet eligibility criteria will be randomized 1:1 to receive either CM310 300mg or matched placebo subcutaneously every two weeks (Q2W) for a total of 8 times. All patients will receive MFNS on a daily basis as a background treatment throughout the study. MFNS is required to use no less than 14 days during Screening/run-in Period.
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 for 16-week treatment |
|
| Placebo | Placebo Comparator | Placebo is given subcutaneously (SC) every two weeks for 16-week treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CM310 | Biological | 300 mg every two weeks |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Bilateral endoscopic Nasal Polyps Score (NPS) | Change from baseline in the bilateral endoscopic NPS.NPS score ranges from 0-8. (sum of 0-4 for each nasal passage scores), higher score means a worse outcome. | at Week 16 |
| Nasal Congestion/Obstruction SymptomSeverity (NCS) Score | Change from baseline in the NCS score. NCS score (0-3), higher score means worse nasal symptom. | at Week 16 |
| 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 nasosinusitis. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Luo Zhang | Beijing Tongren Hospital, CMU | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Chaoyang Hospital, CMU | Beijing | Beijing Municipality | China | |||
| Beijing Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37483544 | Derived | Zhang Y, Yan B, Shen S, Song X, Jiang Y, Shi L, Zhao C, Yang Y, Jiang L, Li J, Ye J, Liu J, Wan L, Yang Y, Chen J, Liu F, Su L, Xu Y, Tan G, Yu S, Zhang Y, Wang L, Liu S, Yan H, Liu W, Chen B, Wang C, Zhang L. Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial. EClinicalMedicine. 2023 Jul 5;61:102076. doi: 10.1016/j.eclinm.2023.102076. eCollection 2023 Jul. |
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| Biological |
300 mg every two weeks |
|
| at Week 16 |
| Volume of the involved area of nasosinusitis on 3D-construction CT scan | Change from baseline in the volume of the involved area of nasosinusitis on 3D-construction CT scan. | at Week 16 |
| Bilateral endoscopic NPS | Change from baseline in the bilateral endoscopic NPS. | at Week 8 |
| Proportion of subjects receiving rescue therapy for nasal polyps | Proportion of subjects receiving rescue therapy for nasal polyps. | Baseline up to Week 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 |
| 22-item Sino-nasal Outcome Test Scores(SNOT-22) score | Change from baseline in SNOT-22 score. SNOT-22 score (0-110). Higher score means a worse outcome. | at Week 16 |
| Total Symptom Score(TSS) score | Change from baseline in TSS score. TSS score (0-9). Higher score means worse nasal symptom. | at Week 16 |
| Bilateral endoscopic NPS | Change from baseline in the bilateral endoscopic NPS in subjects with concurrent asthma. | at Week 16 |
| Bilateral endoscopic NCS | Change from baseline in the NCS in subjects with concurrent asthma. | at Week 16 |
| Safety parameters | Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), etc. | Baseline up to Week 24 |
| Pharmacokinetics(PK) | Trough concentration and exposure. | Baseline up to Week 24 |
| Pharmacodynamics(PD) | Change from baseline in serum biomarker level (TARC, total IgE and eosinophil level). | Baseline up to Week 24 |
| PD(eosinophil level in nasal polyps biospy tissue) | Change from baseline of eosinophil level in nasal polyps biospy tissue. | at Week 16 |
| Anti-drug antibodies(ADA) | Incidence of ADA. | Baseline up to Week 24 |
| Neutralizing antibody (Nab) | Incidence of Nab. | Baseline up to Week 24 |
| Beijing |
| Beijing Municipality |
| China |
| Beijing Renmin Hospital | Beijing | Beijing Municipality | China |
| Beijing Tongren Hospital, CMU | Beijing | Beijing Municipality | China |
| First Affiliated Hospital of Chongqing Medical University | Chongqing | Chongqing Municipality | China |
| Jingzhou Central Hospital | Jingzhou | Hubei | China |
| Renmin Hospital of Wuhan University | Wuhan | Hubei | China |
| Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology | Wuhan | Hubei | China |
| Third Xiangya Hospital of Central South University | Changsha | Hunan | China |
| The First Affiliated Hospital of Nanchang University | Nanchang | Jiangxi | China |
| Affiliated Hospital of Qingdao University | Qingdao | Shandong | China |
| Yantai Yuhuangding Hospital | Yantai | Shandong | China |
| Shandong Second Provincial General Hospital (Shandong ENT hospital) | Jinan | Shangdong | China |
| Renji Hospital of Shanghai Jiaotong University School of Medicine | Shanghai | Shanghai Municipality | China |
| Tongji Hospital of Tongji University | Shanghai | Shanghai Municipality | China |
| Second Hospital of Shanxi Medical University | Taiyuan | Shanxi | China |
| Hospital of Chengdu University of Traditional Chinese Medicine | Chengdu | Sichuan | China |
| West China Hospital of Sichuan University | Chengdu | Sichuan | China |
| Zhejiang Provincial People's Hospital | Hangzhou | Zhejiang | China |
| ID | Term |
|---|---|
| D004194 | Disease |
| D009298 | Nasal Polyps |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009668 | Nose Diseases |
| D012140 | Respiratory Tract Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D011127 | Polyps |
| D020763 | Pathological Conditions, Anatomical |
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