Extension Study for Participants of MACI00206 Study of MACI® for the Treatment of Symptomatic Articular Cartilage Defects of the Knee

Study Overview
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Brief Summary
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To examine the 5-year efficacy and safety of MACI implant, compared with arthroscopic microfracture, in participants who received study treatment in the SUMMIT study for treatment of symptomatic articular cartilage defects of the knee.

Detailed Description
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This study was an open-label, multicenter extension to the SUMMIT study designed to examine the 5-year efficacy and safety of MACI compared to arthroscopic microfracture in the treatment of articular cartilage defects of the knee in participants who received study treatment in the SUMMIT study. Follow-up to 2 years post-study treatment was completed as part of the SUMMIT study. Follow-up from 3 to 5 years post-study treatment in SUMMIT was completed in this extension study. All 144 participants who received study treatment in the SUMMIT study were eligible for enrollment into this extension study. Participants had until the end of the visit window for the last visit of this extension study (ie, Week 260 + 6 weeks) to consent to enter this extension study. Efficacy and safety assessments were performed at scheduled visits 3, 4, and 5 years following treatment in SUMMIT (ie, at Weeks 156, 208, and 260 postarthrotomy for patients treated with MACI implant or at Weeks 156, 208, and 260 postarthroscopy for patients treated with microfracture).

Official Title
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An Extension Protocol for Participants of Genzyme-Sponsored Prospective, Randomized, Open-Label, Parallel-Group, Multicenter Study of MACI® for the Treatment of Symptomatic Articular Cartilage Defects of the Femoral Condyle Including the Trochlea

Conditions
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Articular Cartilage Defects

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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Randomized and received study treatment (MACI or microfracture) in the SUMMIT study.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MACI<br>autologous cultured chondrocytes on porcine collagen membrane implant received in previous MACI00206 study | Biological: autologous cultured chondrocytes on porcine collagen membrane<br>* Implantation received in the previous MACI00206 study<br>* Other names: matrix applied characterized autologous cultured chondrocytes;|
| Microfracture<br>Microfracture treatment received in previous MACI00206 study | Procedure: Microfracture<br>* Arthroscopic Microfracture treatment received in the previous MACI00206 study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (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. | MACI00206 Baseline to Week 156 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From MACI00206 Baseline for the Participant's 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. | MACI00206 Baseline and Week 260 | 
| Magnetic Resonance Imaging (MRI) Assessments of Degree of Defect Fill | MRI was assessed by the independent blinded evaluators by means of consensus. The number of participants with a degree of defect fill of >50% is reported. | Week 260 | 
| Proportion of Patients Who Achieve at Least a 10-point Improvement From MACI00206 Baseline in KOOS Pain and Function (Sports and Recreational Activities) Scores | 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 MACI00206 Baseline scores. | Up to week 260 | 
| The Proportion of Patients in Each Treatment Group Assessed as Treatment Failures | 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 ACI. | Years 2 through 5 post treatment (MACI or microfracture) | 
| Average Time to Treatment Failure | ANALYSIS NOT DONE: The planned analyses concerning time to treatment failure were not conducted due to the small number of per protocol treatment failure cases. The number of per protocol treatment failures in each treatment group are reported here. 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 ACI. | Up to 260 weeks | 
| Change From MACI00206 Baseline in the Remaining 3 Subscales (Activities of Daily Living, Quality of Life, and Other Symptoms) of KOOS | 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. | MACI00206 Baseline and Week 260 | 
| Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form | The IKDC Subjective Knee Evaluation Form is a validated knee-specific measure of symptoms, function, and sports activity that is appropriate for patients with a wide variety of knee problems. The form consists of 18 items covering the domains of symptoms, functioning during activities of daily living and sports, and current function of the knee. The IKDC Subjective Knee Evaluation Form is scored by summing the scores for the individual items and then transforming the score to a scale that ranges from 0 to 100. The transformed score is interpreted as a measure of function such that higher scores represent higher levels of function and lower levels of symptoms. A score of 100 is interpreted to mean no limitation with activities of daily living or sports activities and the absence of symptoms. | MACI00206 Baseline and Week 260 | 
| Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the Modified Cincinnati Knee Rating System | The Modified Cincinnati Knee Rating System is a self-assessment of the intensity of sports participation, functional limitations, and the ability to participate in different types of sports. The Modified Cincinnati Knee Rating System overall knee condition score ranges from 1 (poor) to 10 (excellent). | MACI00206 Baseline and Week 260 | 
| Change From MACI00206 Baseline in the 12-Item Short-Form Health Survey (SF-12) Physical and Mental Component Scores | The SF-12 is a subset of the 36-Item Short-Form Health Survey (SF-36) and includes 8 subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) that are used to calculate the physical (PCS) and mental (MCS) summary component scores. MCS and PCS are summarized as Z-scores using standard SF-12 scoring and a US population means. The Z-score indicates how many standard deviations a score is from the population mean. Higher values reflect better health. Changes from Baseline are reported. | MACI00206 Baseline and Week 260 | 
| Change From MACI00206 Baseline in the European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Score | The EQ-5D is a standardized instrument for use as a measure of health outcome (see the EuroQOL Website for details: www.euroqol.org). Applicable to a wide range of health conditions and treatments, it provides a simple descriptive profile and a single index value for health status. The EQ Visual Analogue Scale (VAS) was used to record the respondents' self-rated health status on a vertical graduated (0-100) VAS where 0 is 'the worst health you can imagine' and 100 is 'the best health you can imagine'. | MACI00206 Baseline and Week 260 | 
| Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) |  | Years 2 through 5 post treatment (MACI or microfracture) | 
| Number of Participants Reporting Serious Adverse Events (SAEs) |  | Years 2 through 5 post treatment (MACI or microfracture) | 
| Number of Participants Having Subsequent Surgical Procedures (SSPs) in Target Knee |  | Years 2 through 5 post treatment (MACI or microfracture) | 

 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