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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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031231 |
E.1.2 | Term | Osteochondritis dissecans |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007705 |
E.1.2 | Term | Cartilage damage |
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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 demonstrate superior efficacy and evaluate the safety of MACI implant compared with arthroscopic microfracture in the treatment of patients (aged 18 to 55 years old) with symptomatic articular cartilage defects of the femoral condyle including the trochlea. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
During screening: 1.Provides written informed consent, and is able to read and understand the language and content of the study material. 2.Symptomatic focal cartilage defects as defined by KOOS Pain score <55. 3.Age ≥18 and ≤55 years of age. 4. Agrees to provide a blood sample at the time of cartilage biopsy during the index arthroscopy for testing of HIV-1, HIV-2, hepatitis B, hepatitis C, and syphilis. During Index Arthroscopy: 5.Modified Outerbridge Grade III or IV focal cartilage defect(s) located on the femoral condyles, including the trochlea, that will allow treatment with the same surgical procedure as determined at randomization. Note: concurrent Outerbridge Grade I and II defects are acceptable on the patella or tibia if they remain untreated (or are treated with debridement only) at the time of the arthroscopy and/or arthrotomy. 6.Cartilage lesions determined by arthroscopy prior to randomization and treatment with at least 1 defect size ≥3.0 cm2 on the femoral condyles and/or the trochlea (including osteochondritis dissecans lesions that do not require a bone graft). 7.Stable 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 or concurrent with arthroscopy and/or arthrotomy. 8.Intact meniscus or partial meniscus (at least 50% of functional meniscus remaining). Meniscal repair or resection may be performed either staged or concurrent with the cartilage repair procedure provided that the surgeon is able to confirm that at least 50% of functional meniscus would remain after the corrective meniscal treatment.
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E.4 | Principal exclusion criteria |
At Screening visit: 1.Any surgery on the knee joint within 6 months prior to Screening (not including diagnostic arthroscopy). 2.Symptomatic musculoskeletal conditions in the lower limbs that could impede measurement of efficacy for the target knee joint. 3.In the target knee joint, patient requires or has a history of a total meniscectomy or meniscal allograft, or has a bucket handle tear or displaced tear that requires a meniscectomy removing >50% of the meniscus. 4.Malalignment requiring an osteotomy to correct tibial-femoral or patella–femoral alignment. Retinaculum releases are allowed if indicated to correct patella maltracking. 5.History of osteoarthritis (Kellgren-Lawrence Grade 3 or 4) in the target knee joint, as diagnosed by clinically appropriate X-rays obtained at the screening visit or within the previous 12 weeks. 6.Concomitant inflammatory disease or other condition that affects the joints (e.g., rheumatoid arthritis, metabolic bone disease, psoriasis, gout, symptomatic chondrocalcinosis). 7.History of septic arthritis in the target knee joint within 1 year prior to Screening. 8.Current malignancy or treatment for malignancy within the past 5 years, except nonmelanoma skin cancer. 9.Known history of anaphylaxis to gentamicin or any of the products used in the preparation and use of MACI implant. 10.Patients who, in the opinion of the investigator, have significant medical or psychosocial problems that warrant exclusion. Examples of significant problems include but are not limited to: Any condition that has potential for negatively impacting intra or post-operative course (including: conditions that could severely impair wound healing, e.g., peripheral vascular disease (PVD); Conditions that limit compliance with rehabilitation program, e.g., unstable or poorly controlled angina; Active infection, including unexplained fever (temperature >38.1°C) or antibiotic therapy within 1 week prior to Screening; Any condition that has potential for significantly limiting patient’s ability to assess post-operative knee function, e.g., PVD with symptomatic claudication; Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up, or compliance with any aspect of the study; Patient is currently abusing drugs or alcohol or, in the opinion of the investigator, at high risk for poor compliance.) 11.Previous investigational drug or device use within 3 months prior to Screening. 12.Females who are pregnant or lactating at the time of Screening (patients must agree to not become pregnant between the Screening visit and the surgical treatment visit, i.e., arthroscopy for those randomized to treatment with microfracture, and arthrotomy for those randomized to MACI implant treatment). 13.Ongoing litigation for compensation for musculoskeletal injuries or disorders. During Index Arthroscopy: 14. Modified Outerbridge Grade III or IV defect(s) located on the patella or tibia.
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E.5 End points |
E.5.1 | Primary end point(s) |
The co-primary efficacy variable is the change from Baseline to Week 104 for the patient’s KOOS Pain and Function (Sports and Recreational Activities) scores. |
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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 | Yes |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Surgical procedure: Microfracture |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | Information not present in EudraCT |
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 subject undergoing the trial |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |