Kolon TissueGene's TG-C Fails to Meet Co-Primary Endpoints in First U.S. Phase 3 Osteoarthritis Trial
核心洞察
TG-C, a first-in-class cell and gene therapy for knee osteoarthritis, failed to demonstrate statistically significant improvements over placebo in VAS pain and WOMAC function scores at 12 months in the ACTiVION-II Phase 3 trial.
The study enrolled 531 patients across 27 U.S. sites; both TG-C and placebo groups showed similar improvements from baseline, with a higher-than-expected placebo response potentially influencing results.
No new safety concerns emerged, and the rate of total knee replacement was lower in the TG-C group (0.6%) compared to placebo (5.3%).
Kolon TissueGene (搜索) announced on July 20, 2026 that TG-C, its investigational first-in-class cell and gene therapy for knee osteoarthritis (OAK), failed to meet its co-primary endpoints in the first of two U.S. Phase 3 clinical trials. The ACTiVION-II study (NCT03291470) showed no statistically significant difference between TG-C and placebo in reducing pain or improving joint function at the 12-month mark, dealing a setback to the company's lead program.
Trial Design and Topline Results
The ACTiVION-II study enrolled 531 patients with Kellgren-Lawrence (KL) grade 2 or 3 moderate knee osteoarthritis across 27 clinical trial sites in the United States. Participants were randomized 2:1 to receive either a single intra-articular injection of TG-C or a saline placebo, with efficacy and safety evaluated over a 24-month period.
At 12 months, the mean reduction in VAS (Visual Analogue Scale) pain score was 38.6 points in the TG-C group compared to 39.1 points in the placebo group. The mean total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score decreased by 26.34 points in the TG-C group versus 27.57 points in the placebo group. Neither difference reached statistical significance. Additionally, the study did not meet any of its key secondary endpoints.
Placebo Response Under Scrutiny
Kolon TissueGene (搜索) attributed the outcome, at least in part, to an unexpectedly robust placebo response. The company noted that both the TG-C and placebo groups demonstrated similar degrees of improvement from baseline in pain and joint function.
"For clinical trials involving diseases such as osteoarthritis that are accompanied by pain — especially when using intra-articular injection — it has been reported that a relatively high placebo response is often observed," the company stated. "We are thoroughly examining these related factors, as these characteristics may have influenced the results in this trial."
Nam Moonjong, CEO of Kolon TissueGene (搜索), added: "In this first trial, the higher-than-expected placebo response appears to have significantly affected result interpretation. We are currently conducting multifaceted and detailed analyses of various variables, including the possibility of site-specific differences identified through additional analyses."
Safety Profile and Joint Replacement Signal
TG-C was generally safe and well-tolerated, with no new or unexpected safety signals identified in the topline results. The overall incidence, severity, and pattern of treatment-emergent adverse events were comparable between the TG-C and placebo groups, with the majority of events reported as Grade 1 or Grade 2 in severity.
Notably, the percentage of patients who required total knee replacement due to worsening osteoarthritis was lower in the TG-C group at 0.6% (2 of 310 patients) compared to 5.3% (8 of 151 patients) in the placebo group.
Looking Ahead to ACTiVION-I
Kolon TissueGene (搜索)'s Phase 3 program for TG-C consists of two independent trials conducted under the same protocol but at different clinical sites, by different investigators, and with different patient populations. Topline results from ACTiVION-I (NCT03203330), the second Phase 3 trial, are anticipated in October 2026.
"The second trial is not a simple repetition of the first but an independent study performed under different conditions, so we are paying close attention to the results to be announced in October," said CEO Nam Moonjong.
Co-CEO Seng Ho Jeon stated: "We are deeply grateful to the study participants, investigators and clinical trial sites for their contributions to the ACTiVION-II study over the last several years. We continue to analyze the full data set for additional insights."
As part of its strategic response, Kolon TissueGene (搜索) intends to appoint orthopedic specialist Andy Weymann, who previously served as Chief Medical Officer for 14 years at Smith & Nephew, as its new CMO. The company plans to refine its future development strategy based on detailed analysis of the ACTiVION-II results.