A Prospective Randomized Controlled Multicenter Phase-III Clinical Study to Evaluate the Safety and Effectiveness of NOVOCART® 3D Plus Compared to the Standard Procedure Microfracture in the Treatment of Articular Cartilage Defects of the Knee
Overview
- Phase
- Phase 3
- Intervention
- NOVOCART® 3D plus
- Conditions
- Traumatic Articular Cartilage Defects in the Knee Joint
- Sponsor
- Tetec AG
- Enrollment
- 263
- Locations
- 35
- Primary Endpoint
- Subjective IKDC score
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
In this phase 3 clinical trial, a second generation ACI (autologous chondrocyte implantation technique) is compared to standard of care therapy (microfracture) to treat traumatic cartilage defects of the knee for efficacy and safety. The investigated study treatment NOVOCART 3D plus is a biphasic biological scaffold which contains cultivated chondrocytes derived from the patient in a previous tissue harvest procedure. Allocation to the study treatment is done by randomization in a ration of 2:1 in favor to ACI (investigational product). Follow-up data for efficacy is collected for 2 years: follow-up visits are performed 6 weeks, 3 months, 6 months, 12 months, 18 months and 24 months after treatment; additional data for safety will be collected for up to 5 years: 36, 48, and 60 months after treatment. The study involves knee surgery (by arthroscopy, or mini-arthrotomically for implantation surgery), and blood withdrawal for safety within the first year after treatment. Initial imaging is required at baseline. Optional MRI imaging and biomarker collection is done as substudy at specific sites only.
Detailed Description
For the cartilage cell product NOVOCART® 3D plus, which is used in the study described here, the company TETEC AG obtained an expanded production authorization from the medication monitoring authorities in compliance with Section 13, Para. 1 of the Medicinal Products Act in 2003. This entitles TETEC AG to produce the pharmaceutical product and already distribute it. More than 6000 patients were already successfully treated with NOVOCART® 3D in Europe since 2003. In order to obtain a general market authorization for NOVOCART® 3D plus, this control group study is conducted, in which the superiority of the safety and effectiveness of carrier-bound Autologous Chondrocyte Transplantation with NOVOCART® 3D plus compared to the standard of care microfracture surgery needs to be proven. This study further aims at developing and validating known and new biologic markers for the quality and clinical efficacy of the product as requested in the context of identity, purity and potency characteristics of the medicinal/investigational product. The patients will receive one of the therapeutic procedures in the study. The treatment procedure which will be used will be decided by a previously specified randomization process. This type of study meets the high quality requirements of the statutorily specified safety and quality regulations which are also referred to as "Good Clinical Practice" (GCP). The probability of the patient being allocated to one of the two treatments is 2:1; that is, an approx. 67% probability of therapy with NOVOCART® 3D plus and an approx. 33% probability of therapy with microfracture. Neither the patient, nor the investigator will be able to influence the treatment assignment. Patients will be screened for eligibility at the Screening Visit. Each patient will remain in the study for 24 months post-implant for the effectiveness assessments, and then an additional three years to complete the planned post-market phase. Each patient will be in the study for up to five years. Cells and tissues collected from this study will be used in other in vitro-controlled experiments aimed at developing and validating known and novel biologic markers to quantify cell quality in the context of identity, purity and potency. Prognostic values of these biologic markers will be examined by correlating them with clinical data collected in this study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient is between 18 and 65 years old at screening OR (in selected countries only) is a pediatric patient (14-17 years old) with closed epiphyseal growth plate (confirmation of closure of epiphyseal growth plate of the index knee by x-ray or MRI required).
- •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.
- •Patient has a defect size is between 2 and 6 cm
- •Note: defect size can be estimated by MRI at visit 1 if no data is available from medical history.
- •Patient has an intact articulating joint surface (not higher than Grade 2 International Cartilage Repair Society classification, no kissing lesions). Note: ICRS classification can be estimated by MRI at visit 1 if no data is available from medical history.
- •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.
- •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).
- •Patient has free range of motion of the affected knee joint or ≤ 10° of extension and flexion loss.
- •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.
- •Patient has a baseline score of 60/100 on the 2000 International Knee Documentation Committee (IKDC) subjective knee evaluation.
Exclusion Criteria
- Not provided
Arms & Interventions
N3D plus
NOVOCART® 3D plus (Autologous Chondrocyte Transplantation System)
Intervention: NOVOCART® 3D plus
Microfracture
Microfracture is the standard care surgery.
Intervention: Microfracture
Outcomes
Primary Outcomes
Subjective IKDC score
Time Frame: Baseline assessment to 24-month follow-up assessment
The primary endpoint is the change from baseline in the "2000 International Knee Documentation Committee" (IKDC) subjective score to 24-month visit. The IKDC will be recorded for NOVOCART® 3D plus and microfracture patients at baseline visit 1 and at the 6 weeks, 3-, 6-, 12-, 24-, 36-, 48,- and 60-month follow-up assessments.
Secondary Outcomes
- IKDC objective physician score(Baseline assessment to 24-month follow-up assessment)
- Knee Injury and Osteoarthritis Outcome Score (KOOS)(Baseline assessment to 24-month follow-up assessment)
- Surgical time (cut-to-suture time)(Transplantation (24 +-5 days post-arthroscopy) and/or arthroscopy (>= 1 day after screening), depending on the study arm)
- MOCART Score (MRI)(Baseline assessment to the 24-month assessment)
- Health-related quality of life as measured by the SF-36 survey(Baseline assessment to 24-month follow-up assessment)
- Length of incision(Only for verum group at transplantation (24 +-5 days post-arthroscopy))
- Any unanticipated adverse event(Baseline assessment up to 60-months follow-up assessment)
- Treatment Failure(From completion of study treatment until 60-months follow-up assessment)