TLC has reported top-line results from the phase I/II trial of TLC599 for sustained pain management in patients with osteoarthritis of the knee. The trial demonstrated a positive safety profile for a single intra-articular injection of either a 6mg or 12mg dose of TLC599. In addition, the trial demonstrated a trend of sustained, clinically meaningful decrease from baseline through week 12 in several widely-used assessments of pain. These results support the potential for TLC599 to address the problem of a limited duration of action for steroid therapy in patients with osteoarthritis.
Therapies for osteoarthritis can be divided into approximately three categories depending on the severity of the disease. Often, physical therapy and non-steroidal anti-inflammatory drugs are used at early stages. As the disease progresses, injectable steroids are a typical treatment option. However, clinical practice guidelines advise against administering injections more than four times a year. These steroids only last for one to two weeks, meaning that many patients suffer from pain for months in between treatments.
“Aging populations across the globe are leading to an increased prevalence of osteoarthritis but current treatment options are inadequate,” commented TLC President George Yeh. “The results of this trial demonstrate that TLC599 may address the critical issue of short duration of action that limits the therapeutic potential of corticosteroid treatments in wide use today. We are encouraged by these results as we move ahead with our phase II trial. We are optimistic that TLC599 will ultimately reduce burdens for patients and the healthcare system.”
The randomized, open-label, single-dose study of 40 patients found no significant adverse events over the 12 week period following injection. In addition, results in the 12mg dose group demonstrated a trend of decrease from baseline in subject-rated Visual Analogue Scale (VAS) pain score at each study evaluation at week one, four, eight and 12 (with a -3.14 point mean change from baseline at week 12; p=0.0156; per-protocol (PP) population), consistent with results in patients treated with the 6mg dose (-1.95 point mean change from baseline at week 12; p=0.3125; PP). Results also demonstrated a trend of decrease relative to baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) A pain subset measurement at each study evaluation (a mean change of -3.75 points at week 12; p=0.0625; PP). These measurements were consistent with the trend observed in patients treated with the 6mg dose (a mean change of -1.5 points from baseline in WOMAC A score; p=0.2500; PP). The positive safety profile and sustained efficacy observed in the trial support the potential of TLC599 for further development at 12mg or higher doses.
TLC plans to initiate a phase II trial of TLC599 at sites in Taiwan and Australia, with investigational new drug (IND) approval already granted in Taiwan by the Taiwan Food and Drug Administration (TFDA). The trial will involve 24 weeks of observation following a single intra-articular injection of TLC599 and investigate sustained control of pain for three groups: placebo, 12mg and 18mg, with 24 patients in each group. WOMAC measurements will be conducted at regular intervals over the observation period to evaluate efficacy of pain management. Data will be un-blinded once the 24 week data are available for all 72 patients. This phase II clinical trial will help to determine the sample size and the efficacy period for a pivotal trial.