TORONTO – A single intra-articular injection of a novel, sustained-release liposomal formulation of dexamethasone in patients with symptomatic knee osteoarthritis brought at least 6 months of pain control in a multicenter, phase 2a trial, David Hunter, MD, reported at the OARSI 2019 World Congress.
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Dr. David Hunter
This is a product that could fill a significant unmet medical need. Current therapies for knee OA have modest efficacy, and the injectable ones provide only 2-4 weeks of benefit. The ability to obtain significant pain relief with just a couple of intra-articular injections per year would be an important therapeutic advance, observed Dr. Hunter, professor of medicine at the University of Sydney.
He presented a 24-week study of 75 patients with symptomatic knee OA randomized at 13 sites in Australia and Taiwan to a single intra-articular injection of either 12 or 18 mg of the liposomal dexamethasone or to normal saline. One knee per patient was treated.
The primary outcome was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 12. The 12-mg formulation of steroid significantly outperformed placebo at that time point as well as at all others. From a mean baseline WOMAC pain score of 1.49 on the 0-4 scale, patients in the 12-mg group averaged reductions of 0.83 points at 12 weeks, 0.85 at both weeks 16 and 20, and 0.87 at week 24. A statistically significant between-group difference was seen as early as day 3 after injection.
More than half (52%) of recipients of the 12-mg dose of liposomal dexamethasone, a product known for now simply as TLC599, maintained at least 30% pain relief at all visits through the study close at 24 weeks, as did 22% of controls, the rheumatologist reported at the meeting sponsored by the Osteoarthritis Research Society International.
The 12-mg injection also proved superior to placebo for the secondary endpoint of change in WOMAC function score. From a mean baseline score of 1.53, recipients of the 12-mg dose had improvements ranging from 0.82 points at week 12 to 0.85 points at week 24.
Of note, total acetaminophen intake over the course of the trial in the 12-mg steroid group was less than one-third of that in controls.
The 18-mg dose didn’t result in significantly greater reduction in pain scores than placebo. This is because dexamethasone release in the higher-dose formulation as presently constituted turned out to be less efficient, Dr. Hunter explained.
The safety profile was closely similar in all three study arms.
In phase 3 clinical trials, TLC599 will be compared with standard intra-articular triamcinolone, according to the rheumatologist.
He reported serving as a consultant to the Taiwan Liposome Company, which sponsored the phase 2a study, as well as to a handful of other pharmaceutical companies.