A Randomized, Double Blind, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy, Safety, PK, PD and Immunogenicity of Subcutaneously Given Multiple-Dose CM310 in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 56
- 试验地点
- 19
- 主要终点
- Bilateral endoscopic Nasal Polyps Score (NPS)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Bilateral endoscopic Nasal Polyps Score (NPS)
时间窗: 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
时间窗: at Week 16
Change from baseline in the NCS score. NCS score (0-3), higher score means worse nasal symptom.
次要结局
- Time to the first response of NPS(Baseline up to Week 24)
- Volume of the involved area of nasosinusitis on 3D-construction CT scan(at Week 16)
- Pharmacokinetics(PK)(Baseline up to Week 24)
- Lund-Mackay score(at Week 16)
- Bilateral endoscopic NPS(at Week 16)
- 22-item Sino-nasal Outcome Test Scores(SNOT-22) score(at Week 16)
- Proportion of subjects receiving rescue therapy for nasal polyps(Baseline up to Week 24)
- University of Pennsylvania Smell Identification Test (UPSIT)(at Week 16)
- Bilateral endoscopic NCS(at Week 16)
- Safety parameters(Baseline up to Week 24)
- PD(eosinophil level in nasal polyps biospy tissue)(at Week 16)
- Anti-drug antibodies(ADA)(Baseline up to Week 24)
- Neutralizing antibody (Nab)(Baseline up to Week 24)
- Total Symptom Score(TSS) score(at Week 16)
- Pharmacodynamics(PD)(Baseline up to Week 24)