Prospective, Multicenter, Single-arm Phase III Clinical Trial to Evaluate the Efficacy and Safety of NOVOCART® Inject Plus in the Treatment of Cartilage Defects of the Knee
Overview
- Phase
- Phase 3
- Intervention
- NOVOCART® Inject plus
- Conditions
- Cartilage Defects of the Knee
- Sponsor
- Tetec AG
- Enrollment
- 100
- Locations
- 20
- Primary Endpoint
- Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5). The KOOS score ranges from 0 to 100 (100 indicating no symptoms and 0 indicating extreme symptoms).
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
Prospective, Multicenter, Single-arm Phase III Clinical Trial to Evaluate the Efficacy and Safety of NOVOCART® Inject plus in the Treatment of Cartilage Defects of the Knee. The primary objective of this trial is to demonstrate efficacy of NOVOCART® Inject plus for the treatment of cartilage defects of the knee based on the Knee injury and Osteoarthritis Outcome Score (KOOS) responder rate 24 month after transplantation.
Detailed Description
The present study is a prospective, multicenter, single-arm phase III clinical trial to evaluate the efficacy and safety of NOVOCART® Inject plus in the treatment of patients with focal cartilage defects of the knee (medial or lateral femoral condyle or tibial plateau, trochlea or patella). The study will include adult patients between 18 and 65 years of age and pediatric patients (14 to 17 years) with closed epiphysis. A total of 96 patients will be enrolled in the NOVOCART® Inject plus trial at about 20 clinical study sites in Europe. It is expected that each study site will enroll 3 to 9 patients. The trial will consist of three phases (including screening, treatment and follow-up phase) with a maximum duration of 5 years and 4 months. The treatment with NOVOCART® Inject plus requires 2 surgeries. During the first surgery autologous chondrocytes for transplant production will be harvested arthroscopically, then NOVOCART® Inject plus will be transplanted during a second surgery about 3 to 4 weeks later. In general, NOVOCART® Inject plus transplantation can be performed arthroscopically. However, depending on the defect localization, mini-arthrotomy may be indicated. Eligibility will be assessed preoperatively at visit 1 (screening) and (up to a maximum of 3 months later) intraoperatively during the first arthroscopy (visit 2). During visit 2, cartilage biopsy samples will be taken from eligible patients and sent to TETEC AG for NOVOCART® Inject plus manufacturing. Transplantation will then be performed during a second arthroscopy 3 to 4 weeks later (visit 3). All patients will be followed up for 5 years post NOVOCART® Inject plus transplantation with assessments at 3, 6, 12, 18, 24, 36, 48 and 60 months as outlined in the schedule of events and treatment at the end of this synopsis. NOVOCART® Inject plus will be applied in conjunction with a rehabilitation program according to the rehabilitation regimen defined in the clinical study protocol. The primary and secondary endpoints will be assessed after a follow-up of 24 month post NOVOCART® Inject plus transplantation (primary analysis). Long-term data will be assessed after an additional 3 years follow-up (follow-up analysis). An interim analysis of efficacy and safety data will be performed when 63 patients (66% of the planned number of patients) are evaluable for the primary endpoint.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient is ≥ 18 and ≤ 65 years old at screening. Pediatric patients (14 to 17 years) with closed epiphysis may be included in selected countries. Closure of the distal femoral epiphysis of the target knee needs to be confirmed by MRI or x-ray.
- •Patients with focal articular cartilage defect(s) of the femoral condyle (medial or lateral), the trochlea, the patella or the tibial plateau (medial or lateral) of the knee.
- •Patient has one or two defects in the target knee with a defect-grade of III or IV according to the International Cartilage Repair Society (ICRS) classification or grade III or IV ICRS classification of osteochondritis dissecans lesions (ICRS-OCD).
- •If the patient has only one grade III or IV defect, the size of the defect is ≥ 4 and ≤ 12 cm2 post debridement. If the patient has two grade III or IV cartilage defects the total defect size is ≥ 4 and ≤ 12 cm2 post debridement. The defects must be located on different, knee joint areas and both cartilage defects are to be treated with NOVOCART® Inject plus.
- •Patient has an intact, well contained chondral structure surrounding the defect (i.e. no diffusely thinned-out cartilage surface) and an articulating joint surface opposite to the defect(s) to be treated (≤ Grade I ICRS or ICRS-OCD classification).
- •Patient has intact menisci in the target knee; a maximum of 50% resection per meniscus is allowed. Completely healed meniscal transplants are accepted.
- •Patient has a stable knee joint or sufficiently reconstructed ligaments and no patella malalignment or a sufficiently corrected patella malalignment. Ligament repair is accepted, if performed before, during or within 6 weeks after NOVOCART® Inject plus transplantation. Correction of patella malalignment must be performed before or during NOVOCART® Inject plus transplantation.
- •Patient has free range of motion (ROM) of the affected knee joint or ≤ 10° of active extension and flexion loss (compared to the other knee).
- •Patient has a baseline score of \< 65/100 in the overall KOOS (KOOS5).
- •Only for female patients of childbearing potential (sexually mature, pre-menopausal and not surgically sterile): the patient is willing to use a medically accepted method of contraception until the day of NOVOCART® Inject plus transplantation.
Exclusion Criteria
- •Patient is unable to undergo magnetic resonance imaging (MRI).
- •Patient has grade II cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
- •Patient has more than 2 grade III or IV cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
- •The cartilage defects (ICRS or ICRS-OCD grade I or III or IV) affect more than 3 out of 6 joint areas1 of the target knee.
- •Patient had a prior biologic reconstructive procedure (e.g. microfracture, mosaicplasty, chondrocyte transplantation) in the target knee at a location different from the defect location to be treated in the study. Prior biologic reconstructive procedures are accepted, if the previously treated defect is the same defect that is planned to be treated with NOVOCART® Inject plus (i.e. the prior method has failed) and these procedures were performed ≥ 24 months prior to screening visit
- •Patient had other prior surgical interventions interfering with the assessment of the NOVOCART® Inject plus treatment. Prior diagnostic arthroscopies with debridement and lavage are acceptable.
- •Patients with subchondral bone defects more than 2 mm deep (after resection of affected bone) unless adjuvant defect filling will be performed before or during NOVOCART® Inject plus transplantation.
- •Patient has degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade \>
- •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.
Arms & Interventions
Treatment with NOVOCART® Inject plus
Treatment with NOVOCART® Inject plus (Autologous chondrocyte transplantation)
Intervention: NOVOCART® Inject plus
Outcomes
Primary Outcomes
Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5). The KOOS score ranges from 0 to 100 (100 indicating no symptoms and 0 indicating extreme symptoms).
Time Frame: 24 month
Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5) defined as the average of the 5 subscale scores (ensuring identical weight from all subscales) at the 24 months follow-up assessment. The KOOS5 responder rate is defined as the proportion of patients with ≥ 10 points improvement in the KOOS5 from baseline to the 24 months visit.
Secondary Outcomes
- Change in the KOOS5(24 month)
- Change in the 5 individual subscores of the KOOS(24 month)
- Patient satisfaction with treatment. Patients will be asked 4 questions (with 3 answer options each) related to their treatment satisfaction, no score provided.(24 month)
- Change in the grading according to the IKDC surgeons part(24 month)
- Morphological assessment of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score(24 month)
- Treatment-related adverse events (AEs)(24 month)
- Change in the International Knee Documentation Committee (IKDC) subjective score. The IKDC score ranges from 0 to 100, with 100 indicating the absence of symptoms and higher levels of functioning.(24 month)
- Change in EQ-5D-5L. The components are the EQ-5D-5L index ranging from <0 (worse than dead) to 1 (full health) and a visual analogue scale with the end points of 0 (worst health) and 100 (best health).(24 month)
- Change in activity level/ functional status. Patient questionnaire on activity (sporting habits) and functional status (degree of restriction in general), no score provided.(24 months)
- Biochemical MR assessment by T2 mapping(24 month)
- Time to treatment failure(24 month)
- Treatment failure rate(24 month)