Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: Two-Year Results of a Prospective, Multicenter, Single-Arm Phase III Trial

P Niemeyer, M Hanus, J Belickas, T László, R Gudas, M Fiodorovas, A Cebatorius, M Pastucha, P Hoza, K Magos, K Izadpanah, L Paša, G Vásárhelyi, K Sisák, M Mohyla, C Farkas, O Kessler, S Kybal, R Spiro, A Köhler, A Kirner, S Trattnig, C Gaissmaier, P Niemeyer, M Hanus, J Belickas, T László, R Gudas, M Fiodorovas, A Cebatorius, M Pastucha, P Hoza, K Magos, K Izadpanah, L Paša, G Vásárhelyi, K Sisák, M Mohyla, C Farkas, O Kessler, S Kybal, R Spiro, A Köhler, A Kirner, S Trattnig, C Gaissmaier

Abstract

Objective: To evaluate the clinical outcome of a hydrogel-based autologous chondrocyte implantation (ACI) for large articular cartilage defects in the knee joint.

Design: Prospective, multicenter, single-arm, phase III clinical trial. ACI was performed in 100 patients with focal full-thickness cartilage defects ranging from 4 to 12 cm2 in size. The primary outcome measure was the responder rate at 2 years using the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results: Two years after ACI treatment, 93% of patients were KOOS responders having improved by ≥10 points compared with their pre-operative level. The primary endpoint of the study was met and demonstrated that the KOOS response rate is markedly greater than 40% with a lower 95% CI (confidence interval) of 86.1, more than twice the pre-specified no-effect level. KOOS improvement (least squares mean) was 42.0 ± 1.8 points (95% CI between 38.4 and 45.7). Mean changes from baseline were significant in the overall KOOS and in all 5 KOOS subscores from Month 3 (first measurement) to Month 24 (inclusive) (P < 0.0001). The mean MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score after 24 months reached 80.0 points (95% CI: 70.0-90.0 points) and 92.1 points in lesions ≤ 5 cm2.

Conclusions: Overall, hydrogel-based ACI proved to be a valuable treatment option for patients with large cartilage defects in the knee as demonstrated by early, statistically significant, and clinically meaningful improvement up to 2 years follow-up. Parallel to the clinical improvements, MRI analyses suggested increasing maturation, re-organization, and integration of the repair tissue.

Trial registration: NCT03319797; EudraCT No.: 2016-002817-22.

Keywords: autologous chondrocyte implantation; cartilage repair; hydrogel; knee; large defects.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.T. received payment for central MRI assessment by TETEC AG. C.G., A.Kö., and A.Ki. are employees of TETEC AG. R.S. is an employee of Aesculap Biologics LLC. All other authors received an investigator fee as outlined in the initial clinical trial authorization documents and accepted by the corresponding ethics committees.

Figures

Figure 1.
Figure 1.
KOOS responder rates over time through Month 24. Vertical error bars indicate the exact 95% confidence intervals according to Clopper and Pearson. P values are derived from the 1-sided exact binomial test of hypotheses H0: Rate ≤ 40% versus H1: Rate >40%. KOOS = Knee Injury and Osteoarthritis Outcome Score.
Figure 2.
Figure 2.
Scatter plot with linear regression model for overall KOOS change from baseline at Month 24 by prior failed cartilage repair. KOOS = Knee Injury and Osteoarthritis Outcome Score.

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