E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic Articular Cartilage Defects of the Femoral Condyle including the Trochlea.
Osteochondritis dissecans lesions that do not require a bone graft. |
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E.1.1.1 | Medical condition in easily understood language |
Damage to the cartilage in the knee joint |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031231 |
E.1.2 | Term | Osteochondritis dissecans |
E.1.2 | System Organ Class | 100000004859 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007705 |
E.1.2 | Term | Cartilage damage |
E.1.2 | System Organ Class | 100000004863 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to examine the 5-year efficacy and safety of Matrix-Induced Autologous Chondrocyte Implantation (MACI® Implant), compared with arthroscopic microfracture, in patients who received study treatment in Genzyme-sponsored study MACI00206 for treatment of symptomatic articular cartilage defects of the femoral condyle, including the trochlea. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet the following criteria to participate in this extension study:
1. Received study treatment (MACI implant or microfracture) in the MACI00206 study.
2. Provides written informed consent. |
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E.4 | Principal exclusion criteria |
Exclusion Criteria, not applicable for this extension study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy will be assessed by evaluation of:
•Co-primary efficacy variable
Change from MACI00206 Baseline to Week 156 for the patient’s Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain and Function (Sports and Recreational activities) scores.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary efficacy variables
• Change from MACI00206 Baseline to Weeks 24, 36, 52, 78, 104, 208 and 260 for the patient’s KOOS Pain and Function (Sports and Recreational activities) scores.
• Magnetic resonance imaging (MRI) assessments of structural repair parameters at Weeks 52, 104, 156 and 260 including:
o Degree of defect fill based on the thickness of repair tissue; defect fill is to be regarded as the principal MRI indicator of response to treatment
o Degree of integration of the repair tissue with adjacent native cartilage
o Signal intensity of the repair tissue relative to adjacent native cartilage
• Response rate based on KOOS Pain and Function (Sports and Recreational activities) scores: the proportion of patients who responded to treatment at Weeks 24, 36, 52, 78, 104, 156, 208 and 260. A responder is defined as a patient with at least a 10-point improvement in both the KOOS Pain and
Function (Sports and Recreational activities) scores from MACI00206 Baseline (Roos, 2003, Health Qual Life Outcomes).
• Treatment failure rate: the proportion of patients in each treatment group assessed as treatment failures at Weeks 24, 36, 52, 78, 104, 156, 208 and 260.
• Average time to treatment failure: the time to treatment failure will be based on the date that the physician decides that surgical re-treatment of the original index lesion is required relative to the date of the original study surgery (i.e., arthroscopy for microfracture and arthrotomy for MACI implant).
Treatment failure is only determined in relation to the original treated defect(s).
• Change from MACI00206 Baseline at Weeks 24, 36, 52, 78, 104, 156, 208 and 260 in the remaining 3 subscales of the KOOS instrument (i.e., other Symptoms, Knee-Related Quality of Life [QOL], Activities of Daily Living [ADL]).
• Change from MACI00206 Baseline at Weeks 52, 104, 156, 208 and 260 in the patient’s evaluation of overall knee condition using the Modified Cincinnati Knee Rating System.
• Change from MACI00206 Baseline at Weeks 52, 104, 156, 208 and 260 in the patient’s evaluation of overall knee condition using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form.
• Change from MACI00206 Baseline at Weeks 52, 104, 156, 208 and 260 in the 12-Item Short-Form Health Survey (SF-12) Acute Version 2.0 for the 8 subscales (physical functioning, role-physical, bodily pain, general health, vitality, social function, role-emotional, mental health), and the physical and mental summary components.
• Change from MACI00206 Baseline at Weeks 52, 104, 156, 208 and 260 in the European Quality of Life (EuroQOL) 5 dimensions (EQ-5D) health state. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
156 weeks; 208 weeks; 260 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of the last patient participating in the study |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |