Kolon TissueGene(950160)'s knee osteoarthritis cell and gene therapy candidate "TG-C" failed to demonstrate pain and function improvement over placebo in a phase 3 trial in the United States.
However, in the long-term follow-up safety assessment, no new safety signals were identified, and the company said it plans to discuss the future development direction with the U.S. Food and Drug Administration (FDA) based on additional clinical results.
Kolon TissueGene announced topline results of the phase 3 trial (TG-G 15302 Study) of TG-C conducted in the United States in a disclosure on the 20th.
TG-C (formerly Invossa) is an osteoarthritis treatment under development by Kolon TissueGene, a cell and gene therapy administered into the intra-articular space of the patient's knee. Unlike existing treatments that focus on pain relief, it has been developed to aim at inhibiting cartilage damage and delaying disease progression.
The trial was conducted under U.S. FDA approval to evaluate the efficacy and safety of a single intra-articular injection of TG-C in patients with knee osteoarthritis. It was designed as a randomized, double-blind, placebo-controlled, multicenter study, and a total of 531 patients participated across 27 sites in the United States.
The company evaluated the efficacy of TG-C at 12 months after administration. The co-primary endpoints were: △ change from baseline in VAS (Visual Analogue Scale) pain score △ change from baseline in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) total score.
The analysis found that TG-C did not show a statistically significant improvement over placebo in either of the two primary endpoints.
The VAS pain score decreased by an average of 38.7 points from baseline in the TG-C arm and by 39.2 points in the placebo arm. The between-group difference was 0.5 points, with a 95% confidence interval of -4.3 to 5.3 and a p-value of 0.8322.
The WOMAC total score likewise decreased by 27.61 points in the TG-C arm, compared with 26.54 points in the placebo arm. The between-group difference was -1.07 points, with a 95% confidence interval of -4.75 to 2.62 and a p-value of 0.5701.
Because the p-values exceeded 0.05, the threshold for statistical significance, TG-C failed to prove superior treatment effects over placebo.
However, on safety, the results were consistent with TG-C's previously identified safety profile.
The company said that based on the 104-week data covering the entire study period, no new safety signals or unexpected adverse events were identified in the TG-C arm.
The incidence of treatment-emergent adverse events was 83.9% in the TG-C arm and 78.1% in the placebo arm. The incidence of severe adverse events was 14.8% in the TG-C arm and 11.9% in the placebo arm, and serious adverse events were 10.3% and 8.6%, respectively, showing similar levels between the two arms.
Notably, the overall rate of total knee arthroplasty was lower in the TG-C arm at 0.6%, compared with 5.3% in the placebo arm.
Kolon TissueGene plans to use these results together with findings from another ongoing phase 3 clinical trial in the United States (NCT03203330) as materials for future discussions with the FDA. A company representative said, "Based on the results of this clinical trial, we plan to proceed with discussions with the FDA through a comprehensive analysis together with the results of the ongoing additional clinical trial."