A Multi-Center, Open-Label, Phase 2 Trial to Evaluate the Efficacy and Safety of CartiLife® for Patients With Articular Cartilage Defects in the Knee
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 25
- 试验地点
- 5
- 主要终点
- Change in KOOS (Knee Injury and Osteoarthritis Outcome Score) function (sports and recreational activities)
研究概览
简要总结
To evaluate the safety and efficacy of implanting pellet-type extracellular matrix-associated autologous chondrocytes (CartiLife®) obtained by cultivating costal chondrocytes of the subject with articular cartilage defects of the knee as a result of trauma or degeneration.
详细描述
This open-label, phase 2 study is being conducted to evaluate the safety and efficacy of pellet-type extracellular matrix-associated autologous chondrocytes (CartiLife®) in adults with articular cartilage defects due to trauma or degeneration of the knee. It is hypothesized that CartiLife® treatment will demonstrate structural regeneration and improvement in function and pain at Week 48 compared to baseline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order to be eligible to participate in this study, an individual must meet all of the following:
- •Male or female subjects aged over 18 at the time of signing the Informed Consent form
- •Subject who has a size of the relevant cartilage lesion ≥ 2 cm2 and ≤ 10 cm2 but with a defect area total volume ≤ 4 cm3
- •Subject with isolated International Cartilage Repair Society (ICRS) Grade III or IV chondral lesion on articular cartilage
- •Subject who has a lower extremity alignment within 5 degrees of the neutral weight bearing axis
- •Subject who can move independently and has a mechanically stable knee (normal ligament status)
- •Subject with intact or partial meniscus status (>50% of meniscus)
- •Subject who has KOOS pain value less than 60 at baseline
- •Subject who agrees to actively participate in a rehabilitation protocol and follow-up program
- •Subject who is able to provide informed consent and comply with study requirements
- •Subject who is willing to discontinue any nonsteroidal anti-inflammatory drugs (NSAIDs) except rescue medication (< acetaminophen 4 g per day) 7 days prior to visit
- •Subject who has Body Mass Index (BMI) ≤ 37 kg/m2
- •Female and male subjects of childbearing potential who are willing to use adequate contraception methods for the duration of the trial.
排除标准
- •Individuals who meet any of the following will be excluded from participation in this study:
- •Subject who has inflammatory articular diseases such as rheumatoid arthritis or gout or pseudogout
- •Subject who has radiographic evidence of grade 4 osteoarthritis based on the Kellgren and Lawrence criteria
- •Subject who has received an intra-articular treatment within the last 3 months
- •Subject who has had a surgical procedure on the knees within the last 6 weeks (Subjects can be considered enrollment per the investigator's discretion)
- •Subject who has a condition in another lower extremity joint that interferes with the function of the index knee
- •Subject who would receive a concomitant surgical procedure on the knees at the time of the study treatment
- •Subject whose articular cartilage defect is asymptomatic
- •Subject who has any clinically significant disease, which is judged by the investigator to affect this clinical trial, including but not limited to diabetes not adequately controlled, bleeding diathesis or hematologic disease, endocrinopathies, cardiovascular disease, renal disease (severe renal impairment), autoimmune disease, inflammatory arthritis, and current infectious disease
- •Subject with other diseases including tumors except for cartilaginous defects of joints
- •Subject who has a history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin
- •Subject who participates in concurrent trials or in previous trial within 30 days of signing informed consent
- •Subject who has any radiation therapy or chemotherapy within 2 years prior to screening
- •Subject who is currently pregnant or nursing
- •Subject who has any degenerative muscular, connective tissue or neurological condition or other disease process that would interfere with healing or the evaluation of outcome measures.
- •Subject with known HIV infection, active hepatitis C and/or hepatitis B infection
- •Subject who has ligament instability > Grade 1
- •Subject who is an active drug/alcohol abuser or has a history of alcohol or drug abuse during the last two years.
- •Subject who has significant lab abnormalities for the following parameters (If the value is within 10% of the listed laboratory exclusion criterion value and the value is considered not to be clinically significant by the investigator, the subject can be considered for enrollment):
- •Serum ALT and AST > 3 x upper limit of normal
- •Serum creatinine > 1.5 x upper limit of normal
- •PT/INR out of normal range
- •Hemoglobin < 10 g/dL for female subject and hemoglobin < 11 g/dL for male subject
- •Platelets out of normal range
- •Hemoglobin A1c levels > 9%
研究组 & 干预措施
CartiLife®
Extracellular matrix-associated autologous chondrocytes comprise CartiLife®, composed as pellets (1.1 to 1.8 mm in diameter) in suspension. One pre-filled syringe is implanted per 1 cm3 of defect volume, and fibrin adhesive is applied to fix pellets in place through minimal arthrotomy.
干预措施: Autologous Chondrocyte Implantation (CartiLife®) (Drug)
结局指标
主要结局
Change in KOOS (Knee Injury and Osteoarthritis Outcome Score) function (sports and recreational activities)
时间窗: Week 0 (pre-operation) to Week 48 (post-operation)
The KOOS (Knee Injury and Osteoarthritis Outcome Score) is a reliable and valid patient-reported outcome measurement tool that evaluates both short-term and long-term consequences of knee injury. The 5 separately scored subscales of Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related QOL may enrich clinical and research data interpretation (Roos and Lohmander, 2003; Collins et al, 2011). The score ranges from 0 to 100, with 0 representing extreme problems and 100 representing no problems.
Change in volume fill of cartilage defect score
时间窗: Week 0 (pre-operation) to Week 48 (post-operation)
Volume fill of cartilage defect score from MOCART 2.0 Criteria (Schreiner, et al, 2019). The score is from 0 to 20, with 0 representing "\<25% filling of total defect volume OR complete delamination in situ" and 20 representing "Complete fill OR minor hypertrophy (100% to 150% filling of total defect volume).
次要结局
- Change in Lysholm Score(Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation))
- Change in IKDC (International Knee Documentation Committee) Score(Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation))
- Change in VAS (100mm Pain Visual Analogue Scale)(Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation))
- Change in Tegner Activity Score(Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation))
- Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) Score(Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation))
- Evaluations of MOCART Score(Week 24 and 48 (post-operation))
- Evaluation of T2 mapping(Week 24 and 48 (post-operation))
- Change in pain medication dosage(Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation))
- Change in pain medication frequency(Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation))
- Change in KOOS (Knee injury Osteoarthritis Outcome Score) subscale scores (Pain, Other symptoms, Function in daily living, and knee-related Quality of Life)(Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation))
- Change in KOOS (Knee injury Osteoarthritis Outcome Score) Total Score(Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation))
- Number of subjects with treatment-related adverse events(Week 0 (pre-operation), and up to 24 Months (post-operation))
- Number of subjects with treatment-emergent serious adverse events(Week 0 (pre-operation), and up to 24 Months (post-operation))