A Phase IIb Trial of a Novel Extended-Release Microsphere Formulation of Triamcinolone Acetonide for Intraarticular Injection in Knee Osteoarthritis

Objective. FX006 is a novel, microsphere-based, extended-release formulation of triamcinolone acetonide for intraarticular (IA) injection designed to maintain treatment concentration in the joint and provide prolonged analgesic benefits in patients with osteoarthritis (OA) of the knee. This study was undertaken to compare the analgesic benefits of 2 FX006 doses with saline placebo injection. Methods. In this phase IIb study, participants with knee OA (Kellgren/Lawrence grade 2-3) and average daily pain (ADP) intensity >= 5 to >= 9 (on a 0-10 Numerical Rating Scale) were randomized (1: 1: 1) to receive single IA injections of FX006 32 mg (n = 104) or 16 mg (n = 102) or saline placebo (n = 100). The primary end point was the least squares mean (LSM) change from baseline to week 12 in weekly mean ADP intensity scores for FX006 32 mg versus saline placebo. Results. The primary end point was not met (LSM change at week 12 -3.1 with FX006 32 mg versus -2.5 with saline placebo; LSM difference [95% confidence interval] -0.58 [-1.22, 0.07]) (P = 0.08). However, improvements in ADP intensity were significantly greater with FX006 32 mg than saline placebo at weeks 1-11 and week 13. Improvements in ADP intensity were significantly greater with FX006 16 mg versus saline placebo at weeks 1-9. A dose-response effect in duration of maximal analgesic effect was evident (13 weeks with 32 mg versus 9 weeks with 16 mg), with FX006 32 mg providing increased therapeutic benefit relative to FX006 16 mg. All treatments were well tolerated. Conclusion. Although the primary end point was not met, our findings indicate a prolonged reduction in symptoms with FX006 with an evident dose response and a safety profile similar to saline placebo.