A Prospective, Open-label, Randomized, Concurrent Active-controlled, Longitudinal, Multicenter, Phase 3 Clinical Study of the Safety and Efficacy of MACI in Patients Aged 10 to 17 Years With Symptomatic Chondral or Osteochondral Defects of the Knee
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 33
- 主要终点
- Proportion of Patients Who Achieve at Least a 10-point Improvement From Baseline in KOOS-Child Pain and Function (Sports and Recreational Activities) Scores
研究概览
简要总结
The objective of this study is to compare the efficacy and safety of MACI® vs arthroscopic microfracture in the treatment of participants aged 10 to 17 years with symptomatic articular chondral or osteochondral defects of the knee.
详细描述
This is a 2-year prospective, multicenter, randomized, open-label, parallel group clinical trial; a total of 45 participants, ages 10 to 17 years, will be randomized to receive a 1-time treatment with MACI or microfracture (2:1, 30 MACI:15 microfracture).
After meeting screening criteria at the initial visit, all participants will have a screening arthroscopy to further assess study eligibility. During the screening arthroscopy, participants will be further evaluated against entry criteria. Cartilage lesion size will be measured prior to any cartilage repair procedure and randomization. All participants who meet the eligibility criteria and are considered suitable for treatment in the study will have a cartilage biopsy taken prior to randomization to study treatment. Eligible participants will be randomized during the screening arthroscopy procedure to receive either MACI or microfracture treatment. Participants randomized to microfracture will undergo the procedure during the screening arthroscopy.
All biopsied tissue will be sent to the Vericel manufacturing facility in Massachusetts, where the sample will be processed to isolate the autologous chondrocytes. Cells from participants randomized to the MACI group will be used in the preparation of the MACI implant; cells from participants randomized to the microfracture group will be cryopreserved.
Participants randomized to treatment with MACI will return within 12 weeks of the screening arthroscopy to undergo the chondrocyte implantation procedure via arthrotomy. Participants are to follow a recommended postoperative rehabilitation program and compliance with the rehabilitation schedule will be monitored.
Participants will be followed post-study treatment for 2 years (104 Weeks).
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
- None
入排标准
- 年龄范围
- 10 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 10 to 17 years at the time of planned randomization
- •Symptomatic cartilage or osteochondral defects
- •One or more International Cartilage Repair Society (ICRS) Grade III or IV chondral or unsalvageable osteochondral defects located on the femoral condyles and/or trochlea amenable to treatment with the surgical procedure determined at randomization (MACI or microfracture).
- •Concurrent ICRS Grade I and II defects are acceptable on the tibia if they remain untreated (or are treated with debridement only) at the time of study treatment.
- •Participants with a potentially re-attachable osteochondral fragment, identified by magnetic resonance imaging (MRI) and that has not previously been repaired, may be consented to the study and undergo baseline assessments per protocol and prior to confirmatory arthroscopy (Visit 2). At arthroscopy, an attempt will be made to reattach the osteochondral fragment. If this is successful, the participant will be excluded from the study and deemed an intra-operative screen failure. If the attempted reattachment fails and no other
排除标准
- •apply, the participant may continue in the PEAK study: a MACI biopsy will be taken, the participant will be randomized and treated per protocol.
- •At least 1 defect size ≥1.5 cm2 on the patella, femoral condyles and/or the trochlea; defects include OCD lesions with a bone lesion depth of ≤6 mm and does not require a bone graft.
- •Salvageable OCD lesions must have failed prior conservative and a reparative treatment, and the participant still experiences pain associated with the osteochondral lesion. Participants with defects as a result of trauma or unknown etiology are eligible regardless of prior treatments.
- •Stable target knee (i.e., anterior and posterior cruciate ligaments should be free of laxity as well as stable and intact). Ligament repair or reconstruction procedures are allowed prior to screening arthroscopy.
- •Intact meniscus or partial meniscus (at least 50% of functional meniscus remaining) in the target knee. Meniscal repair or resection might be performed either staged or concurrent with the cartilage repair procedure provided that the surgeon was able to confirm that at least 50% of functional meniscus would remain after the corrective meniscal treatment.
- •Written informed consent
- •Exclusion Criteria:
- •Any surgery on the target knee joint within 6 months prior to Screening (not including diagnostic arthroscopy)
- •Previous investigational drug or device use within 3 months prior to Screening
- •Avascular necrosis of the target knee (other than potential OCD lesion to be treated)
- •Participants with uninvolved open growth plates where the surgery necessitates crossing the growth plate, or where the depth of the lesion crosses the growth plate
- •ICRS Grade III or IV chondral or unsalvageable osteochondral defects located on the tibia or any lesion that is bipolar to the index lesion
- •Malalignment requiring concurrent osteotomy to correct tibial-femoral or patella-femoral alignment (prior guided growth treatment is not exclusionary)
- •Symptomatic musculoskeletal conditions in the lower limbs that could impede measurement of efficacy for the target knee joint
- •Concomitant inflammatory disease or other conditions that affects the joints (eg, rheumatoid arthritis, metabolic bone disease, psoriasis, symptomatic chondrocalcinosis)
- •Known history of septic arthritis in the index knee joint
- •Current malignancy or treatment for malignancy within the past 5 years
- •Known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin
- •Females who are pregnant or lactating
- •Participants who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion. Examples of significant problems included but are not limited to:
- •Any condition that has potential for negatively impacting intra or postoperative course
- •Conditions that limit compliance with rehabilitation program
- •Any condition that has potential for significantly limiting participant's ability to assess postoperative knee function
- •Any condition, psychiatric or otherwise, that would preclude informed consent/assent, consistent follow-up, or compliance with any aspect of the study
- •Participant is currently abusing drugs or alcohol or, in the opinion of the Investigator, at high risk for poor compliance
研究组 & 干预措施
MACI
autologous cultured chondrocytes on porcine collagen membrane
干预措施: MACI (Biological)
microfracture
surgical procedure
干预措施: microfracture (Procedure)
结局指标
主要结局
Proportion of Patients Who Achieve at Least a 10-point Improvement From Baseline in KOOS-Child Pain and Function (Sports and Recreational Activities) Scores
时间窗: Baseline and Week 104
A responder is defined as a participant with at least a 10-point change (improvement) in both the KOOS-Child Pain and Function (Sports and Recreational activities) scores from Baseline scores. The Knee and Osteoarthritis Outcome Score for Children (KOOS-Child) is a validated knee-specific instrument developed to assess the patients' opinion of their knee and associated problems. KOOS consists of 5 subscales: Pain, Function in sports and recreational activities, other Symptoms, Function in activities of daily living (ADL), and knee related Quality of life (QOL).
次要结局
- Change from Baseline in KOOS-Child subscores(Baseline and Week 52)