Repair of localized, full-thickness cartilage defects of the femoral condyle (medial, lateral or trochlea) of 2-6cm². MedDRA version: 20.0 Level: PT Classification code 10052913 Term: Cartilage operation System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 20.0 Level: LLT Classification code 10007705 Term: Cartilage damage System Organ Class: 100000004863 MedDRA version: 20.0 Level: LLT Classification code 10057104 Term: Cartilage repair System Organ Class: 10042613
Conditions
Interventions
Product Name: NOVOCART® 3D plus
Product Code: N3D
Pharmaceutical Form: Living tissue equivalent
INN or Proposed INN: NOVOCART® 3D plus
Current Sponsor code: N3D
Other descriptive name: AUTOLOGOUS HUMA
Sponsors
TETEC – Tissue Engineering Technologies – AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Pre-operative inclusion criteria: At visit 1 patients must meet the following inclusion criteria for enrollment; all criteria must be answered with “yes” before the patient is scheduled for arthroscopy: 1. Patient is = 18 and = 65 years old at screening or (in selected countries only) is a pediatric patient (14 to 17 years old) with closed epiphyseal growth plate (confirmation of closure of the epiphyseal growth plate of the index knee by X-ray or MRI required). 2. 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 and the size of each individual lesion is = 2 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. 3. Patient has a defect size = 2 and = 6 cm2. Note: defect size can be estimated by MRI at visit 1 if no data is available from medical history. 4. Patient has an intact articulating joint surface (= Grade 2 International Cartilage Repair Society [ICRS] classification, no “kissing lesions”). Note: ICRS classification can be estimated by MRI at visit 1 if no data is available from medical history. 5. Patient has an intact meniscus; a maximum of 50% resection is allowed. Note: status of meniscus can be estimated at visit 1 if no data is available from medical history. 6. Patient has a stable knee joint or sufficiently reconstructed ligaments. If not, ligament repair must be done before, during or within 6 weeks after cartilage treatment (ACT/microfracture). 7. Patient has free range of motion of the affected knee joint or = 10° of Extension and flexion loss. 8. Patient has a defect-grade of III or IV according to the ICRS classification. Note: ICRS classification can be estimated by MRI at visit 1 if not data is available from medical history. 9. Patient has a baseline score of = 60/100 on the 2000 International Knee Documentation Committee (IKDC) subjective knee evaluation. 10. 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. 11. Mandatory for France only: Patient benefits of a health insurance regimen. Intra-operative inclusion criteria: Patients who are eligible for the study according to the inclusion/exclusion criteria assessed at visit 1 will be scheduled for arthroscopy (visit 2). At visit 2, the following inclusion criteria from visit 1 need to be confirmed; all criteria must be answered with “yes” before the patient is randomized into the study: 1. Patient is not pregnant as confirmed by urine pregnancy test before arthroscopy. 2. 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 and the size of each individual lesion is = 2 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. 3. Patient has a defect size = 2 and = 6 cm2 post-debridement. 4. Patient has an intact articulating joint surface (= Grade 2 International Cartilage Repair Society [ICRS] classification;) no “kissing lesions”). 5. Patient has an intact meniscus; a maximum of 50%
Exclusion criteria
Exclusion criteria: Pre-operative exclusion criteria: At visit 1 none of the following exclusion criteria must apply to any enrolled patient; all criteria must be answered with “no” before the patient is scheduled for arthroscopy: 1. Patient is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study. 2. Patient is unable to undergo magnetic resonance imaging (MRI). 3. Patient has prior surgical treatment of the target knee using mosaicplasty, autologous chondrocyte transplantation and/or microfracture. Note: prior diagnostic arthroscopies with debridement and lavage are acceptable. Ligament repair is accepted, if performed before, during or within 6 weeks after cartilage treatment (ACT/microfracture). 4. Patient has radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade = 2 (see Appendix A). 5. Patient has chronic inflammatory arthritis and/or infectious arthritis. 6. 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. 7. Patient has malalignment (valgus- or varus-deformity) in the target knee. Note: In suspected cases, the mechanical axis must be established radiographically by complete leg imaging in standing position 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 before, during or within 6 weeks after cartilage treatment (ACT/microfracture). 8. Patient has prior surgical treatment of clinical relevance of the target knee. 9. Patient has an osteochondral defect. 10. Patient has bilateral lower limb pain or low back pain. 11. Patient has a known systemic connective tissue disease. 12. Patient has a current uncontrolled diabetes. 13. Patient has a known history of autoimmune disease. 14. Patient has a known history of immunological suppressive disorder or is taking immunosuppressants. 15. Patient is currently systemically or intra-articularly taking steroids and/or has used steroids within the last 30 days prior to screening visit 1. 16. The patient has a history of HIV/AIDS. 17. The patient has a history of syphilis (Treponema pallidum). 18. The patient has an active hepatitis B or C infection with verified antigens. Note: Patients with a cured hepatitis B or C infection and/or verified antibodies are not excluded. 19. The patient has at the site of surgery an active systemic or local microbial infection, eczematization or inflammable skin alterations (including protozoonosis: Babesiosis, Trypanosomiasis (e.g. Chagas-Disease), Leishmaniasis, persistent bacterial infections, like Brucellosis, spotted and typhus fever, other Rickettsiosis, Leprosy, Recurrent Fever, Melioidosis or Tularaemia). 20. Patient has a known history of cancer within the past 5 years. 21. Patient has a known history of osteoporosis; also patients with primary hyperparathyroidism or hyperthyroidism without satisfactory treatment, chronic renal failure or patients with prior pathological fractures independent of the genesis are excluded. 22. Patient has any degenerative muscular or neurological condition that would interfere with evaluation of outcome measures including but not limited to Parkinson’s disease, amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS). 2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 24-month assessment visit. ;Secondary Objective: • 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 and microfracture • To assess surgical parameters. • To assess the proportion of treatment failures;Primary end point(s): The primary endpoint is the patient’s functional outcome as measured by the change in the 2000 IKDC subjective knee score from baseline to the 24-month follow-up assessment. ;Timepoint(s) of evaluation of this end point: From baseline to the 24-month follow-up assessment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline to the 24-month visit in the IKDC objective physician score. • Change from baseline to the 24-month visit in the Knee Injury and Osteoarthritis Outcome Score (KOOS); individual KOOS subscores and KOOS5 (Composite score including all 5 subscores) will be assessed. Proportion of treatment failures at month 24 • Change from baseline to the 24-month visit in the SF-36 to measure clinical utility and summarize health-related quality-of-life and cost-effectiveness. • In vivo performance measured by the 24-month assessment of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score and T2 mapping. These assessments will be performed on a subset of patients (64 in the NOVOCART® 3D plus group and 32 in the microfracture group) as described in section 7.3.3 and in the attached radiological study protocol • Surgical time (cut-to-suture time). • Length of incision (NOVOCART® 3D plus group only). • Proportion of treatment failures at month 24 (see section 7.2.7);Timepoint(s) of evaluation of this end point: See E.5.2. | — |
Countries
Austria, Czech Republic, France, Germany, Hungary, Latvia, Lithuania, Poland, Switzerland, United Kingdom
Contacts
Public ContactClinical Operations
TETEC – Tissue Engineering Technologies – AG
Outcome results
None listed