Single TLC599 injection superior to placebo for knee osteoarthritis pain over 24 weeks
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SAN DIEGO — A single injection of TLC599, a liposomal formulation of dexamethasone sodium phosphate, bested placebo for osteoarthritis knee pain over 24 weeks, while a second injection extended benefits to week 52, according to data.
“While osteoarthritis is the most common joint disorder in the United States, non-surgical treatment options for knee OA are limited,” David Hunter, MD, of Sydney Musculoskeletal Health, at the University of Sydney, told Healio. “Effective, sustained non-surgical treatment options represent an important unmet medical need for this disorder.”
The potential impact of intraarticular injections has not been fully studied, according to Hunter, who presented the data at ACR Convergence 2023.
“Among commonly use therapies, intra-articular injections of corticosteroids can relieve pain, reduce inflammation, and improve mobility, but their effects are not predictable, the duration of pain relief can be short, and the benefit of repeat injections has not been well established,” he said.
In a smaller phase 2 study, a single injection of TLC599 (Taiwan Liposome Company) improved in OA knee pain, and sustained that improvement to 6 months, according to the researchers. To validate these findings in patients with symptomatic knee OA, and examine the potential benefits of a second injection of TLC599 over 1 year, Hunter and colleagues conducted a phase 3 randomized, double-blinded, three-armed, placebo- and active-controlled study. Eligible participants had K-L Grade 2-to-3 knee OA and average daily pain intensity ranging from five to nine on a scale of 0 to 10, as reported from screening diary completion.
A total of 506 participants were randomized 2:1:1 to receive wither TLC599 12 mg, dexamethasone sodium phosphate 4 mg or placebo. At week 24, eligible participants in the TLC599 and placebo arms received a second blinded injection of the same treatment, while patients in the dexamethasone sodium phosphate arm received a blinded injection of TLC599. Outcomes were assessed at multiple time points through week 52. Parameters included average daily pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, as well as Mixed Models for Repeated Measures (MMRM) and Analysis of Covariance (ANCOVA).
According to the researchers, TLC599 was numerically superior to placebo in terms of WOMAC pain at multiple time points through week 24, and statistically superior at week 12 (P < .05). The study drug also bested placebo numerically and statistically at all time points during the first injection period with regard to average daily pain (P < .05). The reduction in average daily pain for TLC599 was additionally superior to dexamethasone sodium phosphate at week 12 (P < .05).
In the second phase of the study, 203 patients who had initially received TLC599, and 94 of those who initially received placebo, received repeat doses those same injections. TLC599 was numerically superior to placebo, as assessed by average daily pain, at all time points between baseline and week 52, and statistically superior through week 34, according to the researchers.
“The current study further validates the benefits of TLC599 in patients with OA of the knee, with sustained benefits in pain reduction using two validated pain measures — average daily pain and WOMAC,” Hunter said. “Compared to the currently available, FDA-approved, extended-release corticosteroids containing triamcinolone acetonide, which did not show an evident treatment effect by week 24, TLC599 further extended the pain reduction effect up to week 24.”
According to Hunter, a second TLC599 injection provided additional sustained benefit in pain reduction.
Safety data demonstrated that all three intervention groups experienced comparable adverse event profiles. A reduction in mean morning serum cortisol levels was reported in patients who received TLC599 at weeks 1 and 25, after the second injection, but these events were deemed to be transient and returned to normal at weeks 2 and 26. Adrenal insufficiency was not observed in any patient.
“The benefits seen with TLC599 in patients with osteoarthritis of the knee suggests that it may also be effective in other disorders including osteoarthritis of the hip and shoulder, and possibly other joints,” Hunter said.
“Non-surgical treatment options for OA of the knee are limited,” he added. “TLC599 has been shown in this study to provide sustained benefit up to 24 weeks after a single injection, and additional benefit following a second injection. It may be an important new non-surgical treatment option for the treatment of patients with OA of the knee.”
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Hunter D. Abstract L19. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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