TRIAL FAIL

Kolon TissueGene's TG-C fails first Phase 3 knee osteoarthritis trial

ACTiVION-II missed both co-primary pain and function endpoints in 531 patients, leaving a second Phase 3 trial due in October 2026 to decide the program's path.

Kolon TissueGene disclosed that TG-C missed both co-primary endpoints, VAS pain and WOMAC total score at Month 12, in the 531-patient ACTiVION-II Phase 3 trial, and also missed all key secondary endpoints.

By AppliedXLJuly 20, 2026Trial NCT03291470

Executive Summary

Kolon TissueGene's Phase 3 trial of TG-C in knee osteoarthritis missed both co-primary endpoints and every key secondary endpoint, with no statistically significant separation from placebo on pain or function.
The trial was a randomized, placebo-controlled, quadruple-masked study of a single injected cell and gene therapy, run under a Special Protocol Assessment agreed with the FDA.
Safety held up: adverse events were comparable between TG-C and placebo, with no new signals, so the miss is an efficacy result, not a safety one.
A second, required Phase 3 trial of the same therapy is due to read out in October 2026, and its result will determine whether the program advances at all.
Cell therapy remains a lightly tested approach in knee osteoarthritis, and this result adds to a mechanism class with no established regulatory precedent in the indication.

The result

TG-C, a single intra-articular injection of allogeneic cell and gene therapy, did not separate from placebo on either co-primary endpoint in ACTiVION-II (NCT03291470). The trial measured change from baseline in VAS pain score and WOMAC total score, a validated composite of pain, stiffness, and physical function, at Month 12. Kolon TissueGene said the study also failed to meet any of its key secondary endpoints, a broader miss than a narrow co-primary shortfall. Co-CEO Moon Jong Noh said the company was "disappointed by the results from the first of two Phase 3 clinical trials of TG-C" but remained "committed to advancing cell and gene therapy innovation targeting osteoarthritis of the knee". NCT03291470+1

How it was tested

ACTiVION-II randomized 531 subjects across 27 U.S. clinical trial sites to a single intra-articular injection of TG-C or placebo, using quadruple masking (patient, caregiver, investigator, and outcomes assessor all blinded) across two arms. Enrollment ran from December 2021 with primary completion recorded on March 6, 2024, and the trial's status moved to completed in May 2026. Adverse events were comparable in incidence, severity, and pattern between TG-C and placebo, with most events graded 1 or 2, and the company said the safety findings were consistent with TG-C's known profile. NCT03291470+1

What comes next

TG-C is being developed under a Special Protocol Assessment with the FDA, an agreement on trial design reached in advance of the pivotal program, comprising two required Phase 3 trials. Kolon TissueGene said it will determine next steps for the program after topline results from the second trial, ACTiVION-I (NCT03203330), expected in October 2026. That second trial is Active, not recruiting, and Kolon TissueGene's only other active trial of the therapy. Because the program depends on both trials under the SPA, the October readout now carries the weight of the entire filing decision. Kolon

The competitive field

Cell and gene therapy is a thinly tested modality in knee osteoarthritis: the closest analogs on record are other cell-therapy programs in earlier-stage or adjacent settings, including Medipost's CARTISTEM in knee cartilage lesions and CellSeed's CLS2901C chondrocyte sheets, neither of which has produced a Phase 3 readout in this specific indication. No approved cell or gene therapy exists for knee osteoarthritis pain; the approved options identified for the indication are topical diclofenac formulations, a different drug class entirely. Against a field where no cell-based mechanism has yet established efficacy in this setting, a second trial that reproduces a clear separation from placebo, on both pain and function, at the same Month-12 timepoint would be the result needed to keep the mechanism viable here.

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.