The drug TLC599 is more effective better than placebo in improving both average daily pain (ADP) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain for patients with osteoarthritis (OA) of the knee, according to new late-breaking data presented at the American College of Rheumatology (ACR) 2023 Convergence.¹

These findings indicated that both ADP and WOMAC pain in individuals with OA of the knee showed improvement following a single injection, and this improvement in pain was sustained up to 24 weeks. The next injection of TLC599 at the 24-week mark led to continued benefits to 52 weeks.

The study was presented by David Hunter, PhD, MBBS, FRACP, from the Sydney Musculoskeletal Health at the University of Sydney. Hunter and colleagues noted that OA of the knee can be relieved by corticosteroid intra-articular injections, as well as reductions in inflammation and greater mobility.

Despite these benefits, the efficacy of such corticosteroids is known to be variable and the relief duration has been frequently shown to be short-lived. The efficacy of repeated injections remains uncertain.

TLC599 is a liposomal formulation of dexamethasone sodium phosphate, and the investigators noted that it was formulated for local injections to allow for extended relief in OA of the knee. The team here sought to validate prior phase 2 findings that demonstrated pain relief in OA patients over 24 weeks and looked at the possibilities for repeat injections over the course of a single-year.

Hunter and colleagues used a randomized, double-blinded, 3-armed, placebo- and active-controlled trial design for the phase 3 study to assess the use of TLC599 in single or repeat doses. The trial involved subjects with knee OA of K-L Grade 2-3, with a ADP ranging from 5 - 9, as reported in the screening diary for the index knee on a scale of 0-10.

The investigators randomized 506 individuals in total in a 2:1:1 ratio, with the subjects being treated with an injection of TLC599 12 mg, an injection of DSP 4 mg, or a saline placebo injection. They gave eligible participants in the placebo and TLC599 groups a second blinded injection of the same type at 24 weeks, but those in the DSP group were given a blinded TLC599 injection.

The research team looked at both effectiveness and safety signals of the drug, which were examined through to 52 weeks. ADP and WOMAC pain were looked into as parameters.

The investigators found that TLC599 was superior to the placebo in ADP both statistically and numerically (P < 0.05), which they found was true across the entire first injection period. They also noted that at the 12-week point, the reduction in ADP with the drug overtook that of DSP (P < 0.05).

The injection of TLC599 also demonstrated numerical superiority with WOMAC pain versus the placebo at all of the time points up to week 24. The investigators reported that statistical significance (P < 0.05) was reached at the primary endpoint of 12 weeks.

Overall, 203 total subjects were given TLC599 injection and 94 who were first given a placebo injection were involved in the research. The research team reported that, up to Week 52, the mean reduction in ADP from the point of baseline for TLC599 was found to be consistently higher than that for placebo, showing statistical superiority up to the 34-week mark.

The team found that the drug showed overall strong tolerability, referencing what they found was a comparable occurrence of adverse events over all 3 treatment arms. By Weeks 1 and 25, following the second injection, the subjects given TLC599 reported a transient decrease in mean morning serum cortisol levels.

The investigators noted, however, that these levels returned to normal by 2 weeks and 26 weeks, and noted that there were no indications of adrenal insufficiency among any of the subjects.

The data offers supplementary insight into the advantages of repeat steroid injections for knee OA, suggesting that TLC599 may help to deliver continued benefits and work as an alternative therapeutic approach for addressing knee pain among OA patients.

References

1. ^{G. Spencer-Green, D. Hunter:, et al. L19: A Phase 3 Study of Repeat Injection of TLC599 in Osteoarthritis of the Knee: Benefits to 52 Weeks. Presented at: American College of Rheumatology Convergence 2023. San Diego, CA. November 10-15, 2023.}