E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Repair of localized, full-thickness cartilage defects of the femoral condyle (medial, lateral or trochlea) of 2-6cm². |
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E.1.1.1 | Medical condition in easily understood language |
Repair of cartilage defects of the knee |
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E.1.1.2 | Therapeutic area | Body processes [G] - Cell Physiological Phenomena [G04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052913 |
E.1.2 | Term | Cartilage operation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057104 |
E.1.2 | Term | Cartilage repair |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064112 |
E.1.2 | Term | Cartilage graft |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
To demonstrate that the effectiveness of the NOVOCART® 3D plus autologous chondrocyte transplantation system is superior to microfracture for the treatment of articular cartilage defects of the knee by demonstrating superiority of the subjective IKDC score improvement from baseline to the score measured at the 36-month assessment visit. |
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E.2.2 | Secondary objectives of the trial |
• To assess the physician evaluation of the functional effectiveness of NOVOCART® 3D plus. • To evaluate health-related quality-of-life improvement. • To evaluate cartilage (tissue-structure) regenerative effects of NOVOCART® 3D plus. • To assess surgical parameters.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
MR Examination Protocols and Data Handling - Document A (attached to the original protocol AAG-G-H-1202) |
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E.3 | Principal inclusion criteria |
• Patient is ≥18 and ≤65 years old at time of screening. • Patient has a localized articular cartilage defect of the femoral condyle or the trochlea of the knee. 2 localized cartilage defects are accepted if the total defect size is ≤6 cm2, both cartilage defects are located at the femoral condyle and/or the trochlea and both cartilage defects are to be treated with NOVOCART® 3D plus or microfracture. • Patient has a defect size ≥2 and ≤6 cm2 post-debridement. • Patient has an intact (≤Grade 2 International Cartilage Repair Society [ICRS] classification) articulating joint surface (no “kissing lesions”). • Patient has an intact meniscus (maximum 1/2-resection). • Patient has a stable knee joint or sufficiently reconstructed ligaments. If not, ligament repair has to be done within 6 weeks to the planned cartilage treatment (ACT/microfracture). • Patient has free range of motion of the affected knee joint or ≤10° of extension and flexion loss. • Patient has a defect of grade III or IV according to the ICRS classification. • Patient has a maximum baseline score of 60/100 on the 2000 International Knee Documentation Committee (IKDC) subjective knee evaluation. • Patient is willing and able to give written informed consent to participate in the study and to comply with all study requirements, including attending all follow-up visits and assessments and postoperative rehabilitation regimen. • Patient benefits of a health insurance regimen |
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E.4 | Principal exclusion criteria |
Only selected (preoperative) exclusion criteria have been listed below. For the complete list see protocol. Preoperative exclusion criteria: • Patient is unable to undergo magnetic resonance imaging (MRI). • Patient has prior surgical treatment of the target knee using mosaicplasty and/or microfracture. (Note: prior diagnostic arthroscopies with debridement and lavage are acceptable). Anterior cruciate ligament repair are accepted, if the target knee is stable or a primary ACL reconstruction is performed within 6 weeks to the planned cartilage treatment (ACT/microfracture). • Patient has radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade ≥2. • Patient has chronic inflammatory arthritis and/or infectious arthritis. • Patient has joint space narrowing >1/3 in the target knee when compared to the other knee or <3 mm joint space measured on X-ray. • Patient has an instable knee joint or unsufficiently reconstructed ligaments. If ligament repair is necessary, the repair has to be performed within 6 weeks to the planned cartilage treatment (ACT/microfracture). • Patient has malalignment (no valgus- or varus-deformity) in the target knee. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in a.p. or rather p.a. projection. The Mikulicz line is not allowed to deviate more than 5 mm of the Eminentia intercondylaris. If alignment is necessary, surgery has to be performed within 6 weeks to the planned cartilage treatment (ACT/microfracture). • Patient has an osteochondral defect. • Patient has bilateral lower limb pain or low back pain. • Patient has a known systemic connective tissue disease. • The patient has a known history of HIV/AIDS. • The patient has a known history of Treponema pallidum (syphilis). • The patient has an active hepatitis B or C infection with verified antigens. Patients with a cured hepatitis B or C infection and/or verified antibodies are not excluded. • The patient has at the site of surgery an active systemic or local microbial infection, eczematization or inflammable skin alterations. • Patient has a known history of cancer. • Patient is taking indomethacin or other NSAIDS as acute anti-pain and/or anti-inflmmatory medication. • Patient has a known history of osteoporosis; also patients with primary hyperparathyroidism, hyperthyroidism, chronic renal failure or patients with prior pathological fractures independent of the genesis. • Patient has a body mass index (BMI) >35 kg/m2.
Intra-operative exclusion criteria: Patients may be excluded intraoperatively during the surgical procedure prior to randomization. None of the following exclusion criteria can apply to any enrolled patient: • Patient has a defect size <2 or >6cm² post-debridement. • Patient has >2 independent cartilage lesions of a total defect size of >6cm² that are not located at the femoral condyle and/or the trochlea in the knee to be treated with NOVOCART® 3D plus or microfracture. • Patient is indicated for concurrent meniscus transplant. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the patient’s functional outcome as measured by the change in the 2000 IKDC subjective knee form scores from baseline to the 36-month follow-up assessment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to the 36-month follow-up assessment. |
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E.5.2 | Secondary end point(s) |
• Change from baseline to the 36-month visit in the IKDC objective physician score. • Change from baseline to 36-month visit in the Knee Injury and Osteoarthritis Outcome Score (KOOS). • In vivo performance measured by the change from baseline to the 36-month assessment of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. These assessments will be performed on a subset of patients (64 in each treatment group) as described in the radiological study protocol. • Change from baseline to the 36-month visit in the SF-36 to measure clinical utility and summarize health-related quality-of-life and cost-effectiveness. • Change from baseline to the 24-month visit in the above patient-reported outcomes. • Surgical time (cut-to-suture time). • Length of incision
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | 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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Czech Republic |
France |
Germany |
Netherlands |
Poland |
Switzerland |
United Kingdom |
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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 patient, last visit and when all study documentation is completed. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
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 |