A Single Dose Escalation Study of Intra-Articular ICM-203 in Subjects With Kellgren-Lawrence Grade 2 or Grade 3 Osteoarthritis of the Knee
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- ICM Co. Ltd.
- 入组人数
- 18
- 主要终点
- Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to determine the safety, tolerability, and activity of ICM-203, a recombinant adeno-associated viral (AAV) vector that expresses a therapeutic gene that promotes cartilage formation, reduces joint inflammation and pain, as well as improves joint physical function, by injecting escalating doses of ICM-203 into the knee of subjects with mild to moderate knee osteoarthritis (OA).
Approximately 6 to 18 subjects will be enrolled into 3 successive dose-escalating groups in a 3+3 study design, whereby 3 study subjects in each group will be dosed sequentially with ICM-203 and 3 additional subjects will be dosed at the same dose level if a dose limiting toxicity (DLT) occurs in any of the first 3 subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body mass index (BMI) of 18.0 to 40.0 kg/m2, inclusive, at the time of screening.
- •Kellgren-Lawrence grade 2 or grade 3 OA of target knee.
- •Target knee pain between 4 and 9, inclusive, on an NRS ranging from 0 (no pain) to 10 (worst pain imaginable), at the time of screening.
- •KOOS function in daily living score >25, a measure of knee function ranging from 0 (extreme problems) to 100 (no problems), at the time of screening .
- •A stable treatment regimen for symptomatic relief of OA, including NSAIDs, for 4 weeks prior to screening.
排除标准
- •History of rheumatoid arthritis, psoriatic arthritis, gout, pseudogout, autoimmune OA, chondrocalcinosis, hemochromatosis, villonodular synovitis, and synovial chondromatosis or other disorder that in the opinion of the Investigator could cause inflammation of the knee.
- •Injection of steroid, hyaluronate or other agent, into the target knee less than 90 days prior to day
- •Major injury to the target knee, such as torn ligament or severe sprain, within 12 months of screening.
- •Disability so severe that the subject cannot comply with the study requirements, including knee symptoms that result in significant difficulty or inability to walk.
- •Surgery on the target knee within 180 days prior to day
- •Total knee arthroplasty or other knee surgery planned in the next 12 months.
- •Active joint infection or other concurrent medical or psychiatric condition that, in the opinion of the Investigator, would make the subject unsuitable for the study.
研究组 & 干预措施
Group 3: ICM-203 (High dose)
3 to 6 subjects will receive a single intra-articular injection of ICM-203 at 6x10e13 vg into the target knee at Day 1
干预措施: ICM-203 (Genetic)
Group 1: ICM-203 (Low dose)
3 to 6 subjects will receive a single intra-articular injection of ICM-203 at 6x10e12 vg into the target knee at Day 1
干预措施: ICM-203 (Genetic)
Group 2: ICM-203 (Medium dose)
3 to 6 subjects will receive a single intra-articular injection of ICM-203 at 2x10e13 vg into the target knee at Day 1
干预措施: ICM-203 (Genetic)
结局指标
主要结局
Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to Week 52
Incidence and Severity of Treatment-Emergent Adverse Events following administration of study drug
Knee function
时间窗: Up to Week 52
Evaluation of change from baseline in knee function as measured using the Knee Injury and Osteoarthritis Outcome Score (KOOS) function in daily living subscale ranging from 0 (extreme problems) to 100 (no problems)
Knee pain
时间窗: Up to Week 52
Evaluation of change from baseline in knee pain as measured using a Numerical Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable)
Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS)
时间窗: Up to Week 52
Evaluation of change from baseline in MOAKS, focusing on articular cartilage and effusion-synovitis
Analgesic use
时间窗: Up to Week 52
Evaluation of change from baseline in in use of analgesics, such as acetaminophen and NSAIDs
Joint space width
时间窗: Up to Week 52
Evaluation of change from baseline in Joint space width in mm as measured on knee radiograph
次要结局
- Cellular immune response to AAV5.2 capsid(Up to Week 52)
- Systemic biodistribution of ICM-203(Up to Week 52)
- Humoral response to AAV5.2 capsid(Up to Week 52)