Kolon TissueGene said its Phase III ACTiVION-II trial of TissueGene-C osteoarthritis therapy (TG-C) in knee osteoarthritis failed to meet its co-primary endpoints, dealing a setback to one of the field’s more advanced regenerative medicine programs.
ACTiVION-II enrolled 531 patients with Kellgren–Lawrence Grade 2 or 3 knee osteoarthritis across 27 US sites and evaluated a single intra-articular injection of TG-C against placebo. The study did not show a statistically significant difference between the treatment and placebo groups in either co-primary endpoint: change from baseline in VAS pain score and WOMAC total score at Month 12.
None of the key secondary endpoints were met. Kolon TissueGene said it will continue analyzing the full dataset, but the topline results showed that TG-C did not improve pain or physical function compared with placebo over 12 months.
Treatment-emergent adverse events were comparable between the two groups in incidence, severity, and pattern. Most were Grade 1 or 2, and no new safety signals were reported.
TG-C is an allogeneic cell and gene therapy comprising genetically modified chondrocytes engineered to express TGF-β1, with the aim of promoting cartilage repair following a single intra-articular injection.
The therapy was approved in South Korea in 2017 under the trade name Invossa but withdrawn from the market in 2019 after a discrepancy was identified in the composition of its cell component. The US development program has proceeded separately under a Special Protocol Assessment agreement with the US FDA, supported by Phase II findings that suggested improvements in pain and mobility and potential effects on structural progression.
Attention now shifts to ACTiVION-I, a companion Phase III study also being conducted under the SPA agreement. Topline results are expected in October 2026, after which Kolon TissueGene said it will determine the program’s next steps.