In patients with knee osteoarthritis, a single injection of the investigation drug FX006 led to greater pain relief than placebo, and persisted for about 2 months for the 20-mg dose and about 3 months for the 40-mg dose, according to results from a phase 2b trial presented at the 2016 Osteoarthritis Research Society International (OARSI) World Congress.
“FX006 is designed to extend the potential of an established therapy [being an] extended-release formulation of triamcinolone acetonide in poly(lactic-co-glycolic acid) microspheres,” explained Philip G. Conaghan, MB, BS, PhD, University of Leeds School of Medicine, Leeds, United Kingdom, speaking here on April 2.
The study included 306 patients with a documented diagnosis of osteoarthritis of the knee. Upon x-ray, the osteoarthritis was required to be Kellgren-Lawrence grade 2 or 3. The pain criterion for study entry was an average daily pain intensity of ≥5 to ≤9 on a numeric rating scale (from 0 = no pain to 10 = pain as bad as you can imagine); the mean score across all patients at baseline was found to be 6.56.
Study treatment was a single intra-articular injection of either FX006 20 mg (n = 102), FX006 40 mg (n = 104), or placebo (n = 100), after which patients were assessed once a week for 24 weeks. The use of acetaminophen (paracetamol) was permitted as rescue medication.
For the primary efficacy endpoint of change from baseline to week 12 in the weekly mean scores for average daily pain intensity, mixed-model repeat-measures (MMRM) analysis did not reveal significant differences between either of the 2 FX006 dose groups compared with placebo (P = .086, 2-sided). At each weekly visit from Weeks 1 to 9, however, the 20-mg dose of FX006 was significantly better than placebo (P < .05, 2-sided) on this measure of pain reduction, as was the 40-mg dose from weeks 1 to 11 and at week 13 (P < .05, 2-sided). From Week 14 onward, the differences between the 3 groups were no longer significant.
Both doses of the active drug “achieved similar maximal analgesic effect at approximately Week 5 post-injection,” said Dr. Conaghan.
In addition, he presented preliminary findings from a phase 3 trial with 3 treatment arms, comparing FX006 40 mg, or standard triamcinolone acetonide suspension 40 mg, or placebo, that used the same definition of primary endpoint as in this phase 2b study. In the phase 3 trial, “FX006 40 mg met the primary endpoint versus placebo at week 12, and provided a clinically meaningful reduction in pain relative to placebo and triamcinolone acetonide suspension,” the investigators reported.
Funding for both studies was provided by Flexion Therapeutics, Burlington, Massachusetts.
Presentation title: Sustained And Profound Analgesic Benefits In People With Osteoarthritis Of The Knee Using FX006, An Intra-Articular Extended-Release Formulation Of Triamcinolone Acetonide: Results From A Double-Blind, Randomized, Parallel-Group, Dose-Ranging Study. Abstract 70]