A Study to Evaluate the Safety, Tolerability and Efficacy of NCR100 Injection for the Treatment of Knee Osteoarthritis（ KOA）
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 162
- 主要终点
- Dose-Limiting Toxicity(DLT)
研究概览
简要总结
This clinical study is to investigate the safety and efficacy of NCR100 injection in subjects with knee osteoarthritis (KOA). It contains two parts dose-escalating, and blind random study in adult KOA subjects.
详细描述
Knee osteoarthritis(KOA) is a kind of degenerative joint disease characterized by chronic inflammation loss of articular cartilage and subchondral bone remodeling.In China, the estimated number of patients diagnosed with KOA reached 37.35millon. The aim of this sudy is to evaluate the safety tolerability and efficacy of human pluripotent stem cell derived mesenchymal stromal cells (NCR100) injection in the treatment of subjects with knee osteoarthritis.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who understand and voluntarily sign the Informed Consent Form（ICF） before the enrolment;
- •Age: 40-65 years old, both genders;
- •Diagnosis of knee osteoarthritis based on American College of Rheumatology criteria;
- •Subjects with KOA who have persistent pain for more than six months
- •Kellgren-Lawrence grade: II-III
排除标准
- •Subjects previously diagnosed of secondary knee osteoarthritis, or those diagnosed with hip/ankle joint disease requiring medical intervention;
- •Suffering from other diseases that impair knee function or joints;
- •Have received stem cell therapy;
- •Have knee injury history;
- •Experienced knee surgery, or plan to undergo knee surgery;
- •Received analgesics to relieve pain before Investigational Medicinal Product(IMP) injections;
- •Have used traditional Chinese medicine to treat KOA within 4 weeks;
- •Have used intra-articular injection of drugs to treat KOA within 12 weeks;
- •Received glucosamine,chondroitin sulfate, or diacetate therapy before investigational drug intervention within 12 weeks;
- •Subjects with acute phase of knee osteoarthritis;
- •Severe deformity of the knee;
- •Known or suspected allergy or a history of allergies;
- •Abnormal results of laboratory examination as follows: Hepatic Insufficiency （Alanine Aminotransferase>2xULN or Aspartate aminotransferase [ast]>2xULN) renal dysfunction (creatinine clearance rate ≤60ml/min or blood urea nitrogen(BUN) > 2× ULN), Coagulation Defects (INR > 1.5) or severe hematological diseases (Grade 3 or above anemia [Hb < 8 g/dL], Grade 2 or above thrombocytopenia platelet count(PLT) < 75×10^9/L) ;
- •BMI≥30kg/m^2
- •Severe systemic infection or local knee joint infection;
- •Have received systemic glucocorticoid therapy before intervention or need to take systemic glucocorticoid therapy during the treatment;
- •Have a history of acute myocardial infarction or severe heart diseases,QT prolongation;
- •Subjects with peripheral or central nervous system disorders that may interfere assessments;
- •Have contraindications to Magnetic Resonance Imaging(MRI)
- •Subjects who are unable to walk on his own;
- •Subjects with alcohol/drug addiction/abuse or mental disorders;
- •Pregnant or lactating, or unable to comply with contraceptives within 6 months after end of study;
- •Have participated in other clinical trials within 12 weeks before the screening;
- •Severe and poorly controlled comorbidities;
研究组 & 干预措施
NCR100 injection
Subjects will receive four injections of NCR100
干预措施: NCR100 (Biological)
0.9% Normal saline
Subjects will receive four injections of 0.9% Normal saline
干预措施: 0.9% Normal saline (Other)
NCR100 injection and 0.9% Normal saline
Subjects will receive two injections of 0.9% Normal saline and two injections of NCR100
干预措施: NCR100 (Biological)
NCR100 injection and 0.9% Normal saline
Subjects will receive two injections of 0.9% Normal saline and two injections of NCR100
干预措施: 0.9% Normal saline (Other)
结局指标
主要结局
Dose-Limiting Toxicity(DLT)
时间窗: 4 weeks after first injection
Number of participants with Dose-limiting toxicity in 28 days
The Western Ontario and McMaster Universities osteoarthritis index(WOMAC)
时间窗: 48 weeks after first injection
Differences of WOMAC scores in changes from baseline between the experimental group and the control group
次要结局
- Adverse Event(AE) or Serious Adverse Event(SAE)(Within 48 weeks of the first infusion)
- Visual analogue scale (VAS)(8 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks)
- Differences in changes from baseline at 8 weeks, 12 weeks, 24 weeks and 36 weeks of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) between the experimental groups and the control group(8 weeks, 12 weeks, 24 weeks and 36 weeks)
- Differences in changes from baseline to 24 weeks and 48 weeks in cartilages with various regions(24 weeks and 48 weeks)