Phase III Study to Evaluate Safety and Effectiveness of NOVOCART 3D Plus vs. Microfracture in Knee Cartilage Defects (N3D)
|ClinicalTrials.gov Identifier: NCT01656902|
Recruitment Status : Active, not recruiting
First Posted : August 3, 2012
Last Update Posted : February 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Traumatic Articular Cartilage Defects in the Knee Joint||Drug: NOVOCART® 3D plus Procedure: Microfracture||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||263 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||May 2013|
|Estimated Primary Completion Date :||May 2019|
|Estimated Study Completion Date :||May 2021|
Experimental: N3D plus
NOVOCART® 3D plus (Autologous Chondrocyte Transplantation System)
Drug: NOVOCART® 3D plus
Two-Step intervention: 1) cartilage cells are collected from the patient during arthroscopy 2) collected cartilage cells are cultivated in a sterile environment, seeded in an organic matrix scaffold and implanted into the defect location (knee, femur)
Other Name: Matrix-associated autologous chondrocyte implantation
Active Comparator: Microfracture
Microfracture is the standard care surgery.
single-step treatment: defect location (knee, femur) is debrided, then bone plate is drilled mechanically to allow cells from the bone marrow to move to the defect location and to develop a scar tissue
Other Name: Microfracture according to Steadman
- 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.
- IKDC objective physician score [ Time Frame: Baseline assessment to 24-month follow-up assessment ]
The IKDC objective physician score will be recorded for both arms at baseline visit 1 and at the 6 weeks, 3-, 6-, 12-, 24-, 36-, 48,- and 60-month follow-up assessments. A sequentially rejecting, hierarchical test procedure will be employed to test these secondary endpoints in the a-priori defined order given here after the test primary efficacy variable was passed.
The change from baseline to the 24-month visit in the IKDC objective physician score and from baseline to the 24-month visit will be evaluated.
- Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: Baseline assessment to 24-month follow-up assessment ]
The KOOS will be recorded for both arms at baseline visit 1 and at the 6 weeks, 3-, 6-, 12-, 24-, 36-, 48,- and 60-month follow-up assessments.
A sequentially rejecting, hierarchical test procedure will be employed to test these secondary endpoints in the a-priori defined order given here after the test primary efficacy variable was passed. The change from baseline to 24-month visit in the Knee Injury and Osteoarthritis Outcome Score (KOOS) and from baseline to 24-month visit will be evaluated.
- MOCART Score (MRI) [ Time Frame: Baseline assessment to the 24-month assessment ]
Another secondary efficacy endpoint is the in vivo performance (grading on quality of cartilage fill) 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 NOVOCART and 32 in microfracture arm).
The MRI will be recorded at 3, 12, 24 and 60 months follow-up visit.
- Health-related quality of life as measured by the SF-36 survey [ Time Frame: Baseline assessment to 24-month follow-up assessment ]Another secondary efficacy endpoint is the 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. The SF-36 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.
- Surgical time (cut-to-suture time) [ Time Frame: Transplantation (24 +-5 days post-arthroscopy) and/or arthroscopy (>= 1 day after screening), depending on the study arm ]The surgical time will be measured in minutes and recorded for NOVOCART® 3D plus patients at arthroscopy (>= 1 day after screening) and transplantation (24 +-5 days post-arthroscopy); for microfracture patients surgical time will be measured in minutes and recorded at arthroscopy (>= 1 day after screening).
- Length of incision [ Time Frame: Only for verum group at transplantation (24 +-5 days post-arthroscopy) ]The length of incision will be measured in cm and recorded for NOVOCART® 3D plus patients at transplantation (24 +-5 days post-arthroscopy)
- Any unanticipated adverse event [ Time Frame: Baseline assessment up to 60-months follow-up assessment ]
Event descriptions, onset, resolution dates, relationship to the IP and procedures of any AEs will be recorded. Each event will be categorized by seriousness and intensity to facilitate complete safety reporting throughout the trial.
While comparisons between treatment groups can be made for each class of AE, there is no statistical hypothesis governing acceptance of this endpoint at the end of the clinical study because of the different AE profiles associated with the two treatment arms.
- Treatment Failure [ Time Frame: From completion of study treatment until 60-months follow-up assessment ]Any event related to a diagnosed failure of the study treatment
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01656902
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|Principal Investigator:||Peter Angele, Prof.||Universitätsklinikum Regensburg|