A Study of MACI in Patients Aged 10 to 17 Years With Symptomatic Chondral or Osteochondral Defects of the Knee

Study Overview
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Brief Summary
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The objective of this study is to compare the efficacy and safety of MACI® vs arthroscopic microfracture in the treatment of patients aged 10 to 17 years with symptomatic articular chondral or osteochondral defects of the knee.

Detailed Description
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This is a 2-year prospective, multicenter, randomized, open-label, parallel group clinical trial; a total of 45 patients, 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 patients will have a screening arthroscopy to further assess study eligibility. During the screening arthroscopy, patients will be further evaluated against entry criteria. Cartilage lesion size will be measured prior to any cartilage repair procedure and randomization. All patients 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 patients will be randomized during the screening arthroscopy procedure to receive either MACI or microfracture treatment. Patients randomized to microfracture will undergo the procedure during the screening arthroscopy. All biopsied tissue will be sent to the Vericel manufacturing facility in Cambridge, Massachusetts, where the sample will be processed to isolate the autologous chondrocytes. Cells from patients randomized to the MACI group will be used in the preparation of the MACI implant; cells from patients randomized to the microfracture group will be cryopreserved. Patients randomized to treatment with MACI will return within 12 weeks of the screening arthroscopy to undergo the chondrocyte implantation procedure via arthrotomy. Patients are to follow a recommended postoperative rehabilitation program and compliance with the rehabilitation schedule will be monitored. Patients will be followed post-study treatment for 2 years (104 Weeks).

Official Title
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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

Conditions
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Chondral Defect, Osteochondritis Dissecans (OCD), Articular Cartilage Defect, Articular Cartilage Disorder of Knee

Intervention / Treatment
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* Biological: MACI
* Procedure: microfracture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). At least 1 defect size ≥1.5 cm2 on the 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. 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. Exclusion Criteria: Any surgery on the target knee joint within 6 months prior to Screening (not including diagnostic arthroscopy) ICRS Grade III or IV chondral or unsalvageable osteochondral defects located on the patella or tibia or any lesion that is bipolar to the index lesion 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 Known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin Females who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MACI<br>autologous cultured chondrocytes on porcine collagen membrane | Biological: MACI<br>* autologous cultured chondrocytes on porcine collagen membrane<br>|
| Active Comparator: microfracture<br>surgical procedure | Procedure: microfracture<br>* Arthroscopic microfracture treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Achieve at Least a 10-point Improvement From Baseline in KOOS-Child Pain and Function (Sports and Recreational Activities) Scores | 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). | Baseline and Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in KOOS-Child subscores | 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). | Baseline and Week 104 | 
| Change from Baseline in KOOS-Child subscores | 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). | Baseline and Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OCD, cartilage, cartilage defect