A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Clinical Trial Evaluating the Efficacy, Safety, and Immunogenicity of GR1802 in Participants With Chronic Rhinosinusitis With Nasal Polyps
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 228
- 试验地点
- 1
- 主要终点
- Change from baseline in nasal polyps score at week 24.
研究概览
简要总结
The goal of this clinical trial is to learn if GR1802 works to treat severe chronic rhinosinusitis with nasal polyps (CRSwNP) in adults. It will also learn about the safety of GR1802. The main questions it aims to answer are:
- Does GR1802 reduce the need for surgery and systemic corticosteroid use？
- What medical problems do participants have when taking GR1802?
Researchers will compare GR1802 to a placebo (a look-alike substance that contains no drug) to see if GR1802 works to treat CRSwNP.
Participants will:
Take GR1802 or a placebo once every 2 weeks for 13months. Visit the clinic once every 2 weeks for checkups and tests. Keep a diary of their symptoms and the dosage and number of times they use mometasone furoate nasal spray.
详细描述
A randomized, double-blind, placebo-controlled, multi-center clinical trial was designed. The clinical trial was divided into 4 stages: screening/introduction period, double-blind treatment period , maintenance treatment period and safety follow-up period.
The clinical trial aimed to evaluate the efficacy, safety and immunogenicity of GR1802 injection in CRSwNP participants.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed as CRSwNP and treated with systemic glucocorticoid within 2 years before screening; and/or those who had undergone surgery for nasal polyps before screening.
- •An endoscopic bilateral NPS at screening/lead-in period and the baseline period of at least 5 out of a maximum score of 8 (with a minimum socre of 2 in each nasal cavity).
- •Nasal congestion/blockade/obstruction with moderate or severe symptom severity at at screening period (score 2 or 3 ) .
- •Willing to sign an informed consent, able to comply with clinic visits and study-related procedures as per protocol.
排除标准
- •Biologic therapy within 5 half-lives or within 10 weeks before baseline.
- •Anti-IL-4Rα antibody before screening.
- •An experimental drug within 5 half-lives or 1 months before baseline.
- •Systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 2 months or 5 half-lives before baseline.
- •Initiation of allergen immunotherapy within 3 months before screening.
- •Participants receiving leukotriene antagonist/modifier before screening unless on continous treatment for at least 30 days.
- •Participants with FEV1 50% or less of predicted normal were excluded.
- •Participants who have undergone any intranasal and/or sinus surgery within 6 months before screening.
- •Acute sinusitis or upper respiratory infection within a defined time period before screening.
- •A nasal cavity tumor (malignant or benign).
- •Evidence of fungal rhinosinusitis.
- •Presence of another diagnosis associated with nasal polyps (i.e., eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, Young's syndrome, cystic fibrosis).
- •Rhinitis medicamentosa.
- •Nasal septal deviation occluding at least one nostril.
- •Antrochoanal polyps.
- •Pregnant or lactating woman.
研究组 & 干预措施
GR1802 group
GR1802 300mg is administrated every 2 weeks (first dose doubled) for a total of 26 doses, of which an additional 2 ml of placebo is given at week 24.
干预措施: GR1802 (Drug)
placebo group
Placebo is administered every 2 weeks for the first 16 weeks. GR1802 is given every 2 weeks from week 24 to W50.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in nasal polyps score at week 24.
时间窗: At week 24
Nasal polyps score score ranges from 0-8 (sum of 0-4 for each nasal passage scores), higher score means a worse outcome.
Change from baseline in nasal congestion score at week 24.
时间窗: At week 24
Nasal congestion score (0-3), higher score means worse nasal symptom.
次要结局
- Change from baseline in reduction/loss of smell at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56 and 60.(From baseline to week 60)
- Change from baseline in University of Pennsylvania Smell Identification Test (UPSIT) at weeks 2, 4, 16, 24, 32, 40, 52 and 60.(From baseline to week 60)
- Change from baseline in Total Nasal Symptom Score (TNSS) at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56 and 60.(From baseline to week 60)
- Change from baseline in nasal congestion score in participants with a high power field of vision < 55 eosinophil granulocytes in nasal polyp tissue at week 24.(At week 24)
- Proportion of participants with improvement by at least 1 point in nasal polyps score at weeks 2、4、8、16、24、32、40、52 and 60.(From baseline to week 60)
- Immunogenicity, include ADA and Nab.(From baseline to week 60)
- Change from baseline in nasal discharge (anterior/posterior) at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56 and 60.(From baseline to week 60)
- Change from baseline in nasal polyps score at weeks 2、4、8、16、32、40、52 and 60.(From baseline to week 60)
- Proportion of participants with improvement by at least 2 point in nasal polyps score at weeks 2、4、8、16、24、32、40、52 and 60.(From baseline to week 60)
- Time to first response (≥1 point improvement) in nasal polyps score.(From baseline to week 60)
- Change from baseline in nasal congestion score at weeks 4、8、12、16、20、28、32、36、40、44、48、52、56 and 60.(From baseline to week 60)
- Proportion of participants with improvement by at least 1 point in nasal congestion score at weeks 4、8、12、16、20、24、28、32、36、40、44、48、52、56 and 60.(From baseline to week 60)
- Proportion of participants with improvement by at least 2 point in nasal congestion score at weeks 4、8、12、16、20、24、28、32、36、40、44、48、52、56 and 60.(From baseline to week 60)
- Change from baseline in Lund-Mackay score at week 24 and 52.(From baseline to week 60)
- Change from baseline in 22-item Sinonasal Outcome Test (SNOT-22) at weeks 2, 4, 8, 16, 24, 32, 40, 52 and 60.(From baseline to week 60)
- Change from baseline in five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) at weeks 4、16、24、40、52 and 60.(From baseline to week 60)
- Change from baseline in nasal endoscopy nasal polyps score in participants with a high power field of vision < 55 eosinophil granulocytes in nasal polyp tissue at week 24.(At week 24)
- Safety parameters.(From baseline to week 60)
- Pharmacokinetics, include Ctrough, etc.(From baseline to week 60)
- Pharmacodynamics.(From baseline to week 60)