Extension Study for Participants of MACI00206 Study of MACI® for the Treatment of Symptomatic Articular Cartilage Defects of the Knee
- Conditions
- Articular Cartilage Defects
- Interventions
- Procedure: MicrofractureBiological: autologous cultured chondrocytes on porcine collagen membrane
- Registration Number
- NCT01251588
- Lead Sponsor
- Vericel Corporation
- Brief Summary
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
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 128
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Microfracture Microfracture Microfracture treatment received in previous MACI00206 study MACI autologous cultured chondrocytes on porcine collagen membrane autologous cultured chondrocytes on porcine collagen membrane implant received in previous MACI00206 study
- Primary Outcome Measures
Name Time Method Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain and Function (Sports and Recreational Activities) Scores. MACI00206 Baseline to Week 156 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.
- Secondary Outcome Measures
Name Time Method Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the Modified Cincinnati Knee Rating System MACI00206 Baseline and Week 260 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).
Change From MACI00206 Baseline in the 12-Item Short-Form Health Survey (SF-12) Physical and Mental Component Scores MACI00206 Baseline and Week 260 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.Proportion of Patients Who Achieve at Least a 10-point Improvement From MACI00206 Baseline in KOOS Pain and Function (Sports and Recreational Activities) Scores Up to week 260 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.
Magnetic Resonance Imaging (MRI) Assessments of Degree of Defect Fill Week 260 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.
The Proportion of Patients in Each Treatment Group Assessed as Treatment Failures Years 2 through 5 post treatment (MACI or microfracture) Patients were considered as a treatment failure if all of the following 5 criteria were met:
1. Patient's global assessment of their knee joint compared to Baseline was the same or worse
2. Physician's global assessment of the patient's knee joint compared to Baseline was the same, worse, or significantly worse.
3. Percent improvement from Baseline in KOOS Pain score was less than 10%.
4. Physician diagnostic evaluation of failure excluded etiologies (eg, meniscal tear) other than failed treatment of the index lesion.
5. 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.Change From MACI00206 Baseline in the European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Score MACI00206 Baseline and Week 260 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'.
Number of Participants Reporting Serious Adverse Events (SAEs) Years 2 through 5 post treatment (MACI or microfracture) Average Time to Treatment Failure Up to 260 weeks 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:
1. Patient's global assessment of their knee joint compared to Baseline was the same or worse
2. Physician's global assessment of the patient's knee joint compared to Baseline was the same, worse, or significantly worse.
3. Percent improvement from Baseline in KOOS Pain score was less than 10%.
4. Physician diagnostic evaluation of failure excluded etiologies (eg, meniscal tear) other than failed treatment of the index lesion.
5. 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.Change From MACI00206 Baseline in the Remaining 3 Subscales (Activities of Daily Living, Quality of Life, and Other Symptoms) of KOOS MACI00206 Baseline and Week 260 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.
Change From MACI00206 Baseline for the Participant's KOOS Pain and Function (Sports and Recreational Activities) Scores MACI00206 Baseline and Week 260 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.
Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form MACI00206 Baseline and Week 260 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.Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) 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)
Trial Locations
- Locations (14)
Polyclinique Saint-Roch
🇫🇷Montpellier Cedex 2, France
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Lekmed Medical Center
🇵🇱Warsow, Poland
Clinique Maussins-Nollet
🇫🇷Paris, France
Kungsbacka Närsjukhus
🇸🇪Kungsbacka, Sweden
Urazova nemocnice v Brne
🇨🇿Brno, Czechia
University Hospital Na Bulovce- Department of Orthopaedic Surgery Postgraduate Medical Institute
🇨🇿Praha 8, Czechia
Hôpital d'instruction des Armées Robert Picqué
🇫🇷VILLENAVE d'ORNON cedex, France
St. Elisabeth Ziekenhuis
🇳🇱Tilburg, Netherlands
St Olavs Hospital
🇳🇴Trondheim, Norway
University Medical Centre of Utrecht, Department of Orthopaedics
🇳🇱Utrecht, Netherlands
Regional Centre of Knee Surgery & Arthroscopy, Regional Hospital of Traumatologic Surgery
🇵🇱Piekary Slaskie, Poland
Orthopaedic & Traumatology of Motor Organs, Independent Public Clinic Hospital
🇵🇱Bydgoszcz, Poland
University of Oxford, Nuffield Dept. of Orthopaedic Surgery
🇬🇧Oxford, United Kingdom