Superiority of MACI® Versus Microfracture Treatment in Patients With Symptomatic Articular Cartilage Defects in the Knee

Study Overview
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Brief Summary
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The objective of this trial is to demonstrate superior efficacy and safety of MACI compared with arthroscopic microfracture in the treatment of patients (aged 18 to 55 years) with symptomatic articular cartilage defects of the knee.

Detailed Description
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This is a prospective, randomized, open-label, parallel-group, multicenter study designed to investigate the outcome of MACI implant versus arthroscopic microfracture in the treatment of articular cartilage defects in the knee in patients between ages of 18 and 55 years. All patients who meet the eligibility criteria and are considered suitable for inclusion will have a cartilage biopsy taken prior to randomization to study treatment. Eligible patients will then be randomized during the index arthroscopy procedure to receive either MACI implant or microfracture treatment. Patients randomized to treatment with MACI implant will return within approximately 4 to 8 weeks of the index arthroscopy to undergo the chondrocyte implantation procedure via arthrotomy. Patients randomized to microfracture will undergo the procedure during the index arthroscopy. Patients will be assessed post-arthroscopy and post-arthrotomy at intervals during 2 years follow-up. Evaluations include adverse events, functional and pain outcomes, arthroscopic and histologic evaluation and magnetic resonance imaging (MRI).

Official Title
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A Prospective, Randomized, Open-label, Parallel-group, Multi-center Study to Demonstrate the Superiority of MACI® Versus Arthroscopic Microfracture for the Treatment of Symptomatic Articular Cartilage Defects of the Femoral Condyle Including the Trochlea.

Conditions
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Articular Cartilage Defect

Intervention / Treatment
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* Biological: autologous cultured chondrocytes on porcine collagen membrane
* Procedure: Microfracture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement Exclusion Criteria: Known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin Severe osteoarthritis of the knee Inflammatory arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders Prior knee surgery (within 6 months), excluding surgery to procure a biopsy or a concomitant procedure to prepare the knee for a MACI implant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: autologous cultured chondrocytes on porcine collagen membrane<br>* Implantation via mini-arthrotomy<br>* Other names: matrix-applied characterized autologous cultured chondrocytes;|
| Active Comparator: Microfracture<br>Microfracture | Procedure: Microfracture<br>* Microfracture performed by arthroscopic surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 104 for the Participant's Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain and Function (Sports and Recreational Activities) Scores. | The KOOS 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). A 5-point Likert scale was used to record the response to each item ranging from 0 (no problems) to 4 (extreme problems). Within each subscale, items were added up and normalized to a value between 0 (extreme problems) and 100 (no problems). Subscales are not combined to calculate a total score. | Baseline and Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological Evaluation of Structural Repair of Evaluable Biopsies Harvested From the Core of the Index Lesion During Arthroscopy at Week 104 | The mean microscopic International Cartilage Repair Society (ICRS) II overall assessment score was used to assess the histology efficacy endpoint. Scoring of the cartilage repair biopsies was completed using the ICRS II histology scoring system (Mainil-Varlet, 2010, Am J Sports Med) by 2 independent pathologists blinded to the patient's assigned study treatment. This scoring system includes 14 parameters, comprising an overall assessment score reported here, as well as 13 other items related to chondrocyte phenotype, tissue structure, and other factors, each scored on a scale from 0 to 100 representing poor to good quality cartilage. | Week 104 | 
| Assessment of Defect Fill by Magnetic Resonance Imaging (MRI) | Number of participants with MRI degree of defect fill > 50%. Evaluation of MRI data was performed by independent central review blinded to the participant's treatment. Appropriate MRI sequences were used to image cartilage repair tissue. | Week 104 | 
| Response Rate Based on KOOS Pain and Function (Sports and Recreational Activities) Scores at Week 104. | A responder is defined as a participant with at least a 10-point improvement in both the KOOS Pain and Function (Sports and Recreational activities) scores from Baseline | Week 104 | 
| Treatment Failure | The planned analyses concerning time to treatment failure were not conducted due to the small number of per protocol treatment failure cases. As such, the number of participants with treatment failure is being reported. Patients were considered as a treatment failure if all of the following 5 criteria were met: Patient's global assessment of their knee joint compared to Baseline was the same or worse Physician's global assessment of the patient's knee joint compared to Baseline was the same, worse, or significantly worse. Percent improvement from Baseline in KOOS Pain score was less than 10%. Physician diagnostic evaluation of failure excluded etiologies (eg, meniscal tear) other than failed treatment of the index lesion. The physician decided that surgical re-treatment of the index lesion(s) was required that involved either extensive debridement for lesion expansion, violation of the subchondral bone, or autologous cultured chondrocyte implantation. | Week 104 | 
| Change From Baseline at Week 104 in the Remaining 3 Subscales of the KOOS Instrument (Activities of Daily Living, Knee-related Quality of Life, and Other Symptoms) | The KOOS 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). A 5-point Likert scale was used to record the response to each item ranging from 0 (no problems) to 4 (extreme problems). Within each subscale, items were added up and normalized to a value between 0 (extreme problems) and 100 (no problems). | Baseline and Week 104 | 
| Participants With Treatment-Emergent Adverse Events |  | Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cartilage legions, symptomatic focal cartilage defects, microfracture, MACI, autologous chondrocyte