Subcutaneously CM310/Placebo in Patients With Chronic Rhinosinusitis With Nasal Polyposis (CROWNS-1)
- Conditions
- Chronic Rhinosinusitis (Diagnosis)Nasal Polyps
- Interventions
- Biological: CM310Biological: Placebo
- Registration Number
- NCT04805398
- Lead Sponsor
- Keymed Biosciences Co.Ltd
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
- Bilateral CRSwNP.
- Prior treatment with systemic corticosteroids (SCS), and/or contraindicate to or intolerance to SCS, and/or with prior surgery to nasal polyps.
- Stable dose of intranasal corticosteroids for at least 4 weeks before screening.
- Ongoing symptoms for at least 4 weeks before screening：1)Nasal congestion/obstruction; 2)Othe symptom, e.g., loss of smell or rhinorrhea.
- Bilateral NPS of ≥5 with a minimum score of 2 in each nasal cavity at screening and at baseline.
- NCS score of 2 or 3 at screening and at baseline.
- Eosinophilic level meets the one of the following criteria: 1) serum eosinophil count ≥6.9% (without concomitant asthma) or ≥3.7% (with concomitant asthma) at screening; 2) absolute count of ≥55 per high power field or percentage of ≥27% in eosinophil level from nasal polyps biospy tissue.
- Contraception.
- 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).
- concurrent disease, e.g., ongoing rhinitis medicamentosa, acute sinusitis, nasal infection or upper respiratory infection, allergic fungal rhinosinusitis, malignancy, uncontrolled chronic disease such as cardivascular diseases, tuberculosis, diabetes etc.
- Allergic or intolerant to mometasone furoate spray or CM310/placebo.
- Significant liver or renal dysfunction.
- Other.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CM310 CM310 CM310 300mg is given subcutaneously (SC) every two weeks for 16-week treatment Placebo Placebo Placebo is given subcutaneously (SC) every two weeks for 16-week treatment.
- Primary Outcome Measures
Name Time Method Bilateral endoscopic Nasal Polyps Score (NPS) at Week 16 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.
Nasal Congestion/Obstruction SymptomSeverity (NCS) Score at Week 16 Change from baseline in the NCS score. NCS score (0-3), higher score means worse nasal symptom.
- Secondary Outcome Measures
Name Time Method Time to the first response of NPS Baseline up to Week 24 Time to the first response of NPS (defined as bilateral endoscopic NPS improved ≥1).
Volume of the involved area of nasosinusitis on 3D-construction CT scan at Week 16 Change from baseline in the volume of the involved area of nasosinusitis on 3D-construction CT scan.
Lund-Mackay score at Week 16 Change from baseline in the Lund-Mackay score on CT scan. The range of LM score is 0-24. Higher score means worse nasosinusitis.
Bilateral endoscopic NPS at Week 16 Change from baseline in the bilateral endoscopic NPS in subjects with concurrent asthma.
22-item Sino-nasal Outcome Test Scores(SNOT-22) score at Week 16 Change from baseline in SNOT-22 score. SNOT-22 score (0-110). Higher score means a worse outcome.
Proportion of subjects receiving rescue therapy for nasal polyps Baseline up to Week 24 Proportion of subjects receiving rescue therapy for nasal polyps.
University of Pennsylvania Smell Identification Test (UPSIT) at Week 16 Change from baseline in UPSIT. UPSIT score (0-40). Higher score means better sense of smell.
Bilateral endoscopic NCS at Week 16 Change from baseline in the NCS in subjects with concurrent asthma.
Safety parameters Baseline up to Week 24 Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), etc.
PD(eosinophil level in nasal polyps biospy tissue) at Week 16 Change from baseline of eosinophil level in nasal polyps biospy tissue.
Anti-drug antibodies(ADA) Baseline up to Week 24 Incidence of ADA.
Neutralizing antibody (Nab) Baseline up to Week 24 Incidence of Nab.
Total Symptom Score(TSS) score at Week 16 Change from baseline in TSS score. TSS score (0-9). Higher score means worse nasal symptom.
Pharmacokinetics(PK) Baseline up to Week 24 Trough concentration and exposure.
Pharmacodynamics(PD) Baseline up to Week 24 Change from baseline in serum biomarker level (TARC, total IgE and eosinophil level).
Trial Locations
- Locations (19)
Beijing Chaoyang Hospital, CMU
🇨🇳Beijing, Beijing, China
Zhejiang Provincial People's Hospital
🇨🇳Hangzhou, Zhejiang, China
Beijing Hospital
🇨🇳Beijing, Beijing, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
First Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
Jingzhou Central Hospital
🇨🇳Jingzhou, Hubei, China
Beijing Renmin Hospital
🇨🇳Beijing, Beijing, China
Beijing Tongren Hospital, CMU
🇨🇳Beijing, Beijing, 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
Yantai Yuhuangding Hospital
🇨🇳Yantai, Shandong, China
Tongji Hospital of Tongji University
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Affiliated Hospital of Qingdao University
🇨🇳Qingdao, Shandong, China
Second Hospital of Shanxi Medical University
🇨🇳Taiyuan, Shanxi, China
Shandong Second Provincial General Hospital (Shandong ENT hospital)
🇨🇳Jinan, Shangdong, China
Hospital of Chengdu University of Traditional Chinese Medicine
🇨🇳Chengdu, Sichuan, China
Renji Hospital of Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan, China