Neil Bodick1, Joelle Lufkin1, Christina Willwerth1, Anjali Kumar1, James Bolognese2, Chris Schoonmaker2, Rahul Ballal1, David Hunter3, Michael Clayman1. 1. Flexion Therapeutics, 10 Mall Road, Suite 301, Burlington, MA 01803. E-mail address for N. Bodick: nbodick@flexiontherapeutics.com. 2. Cytel, 675 Massachusetts Avenue, Cambridge, MA 02139. 3. Institute of Bone and Joint Research, Kolling Institute, University of Sydney, and Rheumatology Department, Royal North Shore Hospital, Admin 7C, Pacific Highway, St. Leonards, Sydney, NSW 2065, Australia.
Abstract
BACKGROUND: Intra-articular corticosteroids are a mainstay in the treatment of knee osteoarthritis, and in clinical trials, they demonstrate a large initial analgesic effect that wanes over one to four weeks with the rapid efflux of drug from the joint. The present study was undertaken to determine if FX006, an extended-release formulation of triamcinolone acetonide, can provide pain relief that is superior to the current standard of care, immediate-release triamcinolone acetonide. METHODS: In this Phase-2, double-blind, multicenter study, 228 patients with moderate to severe knee osteoarthritis pain were randomized to a single intra-articular injection of FX006 (containing 10, 40, or 60 mg of triamcinolone acetonide) or 40 mg of immediate-release triamcinolone acetonide. Data on the mean daily pain on the 11-point Numeric Rating Scale were collected over twelve weeks; the primary efficacy end point was the change from baseline to each of eight, ten, and twelve weeks in the weekly mean of the mean daily pain intensity scores analyzed with a longitudinal mixed-effects model. RESULTS: The 10-mg dose of FX006 produced pain relief that was improved relative to immediate-release triamcinolone acetonide at two through twelve weeks, although the difference in pain relief was not significant (p ≥ 0.05). The 40-mg dose of FX006 produced pain relief that was improved at two through twelve weeks and was significantly superior to immediate-release triamcinolone acetonide at five to ten weeks (p < 0.05 at each time point). At the 40-mg dose of FX006, prespecified secondary analyses, including responder analyses and all Western Ontario and McMaster Universities subscales, were significantly superior (p < 0.05) to immediate-release triamcinolone acetonide at eight weeks, and the time-weighted mean pain relief (assessed with mean daily pain intensity scores) was significantly superior to immediate-release triamcinolone acetonide over one to twelve weeks (p = 0.04). The 60-mg dose did not provide additional improvement relative to the 40-mg dose. Adverse events were generally mild and similar across all treatments. CONCLUSIONS: Intra-articular injection of FX006, an extended-release formulation of triamcinolone acetonide, provided a clinically relevant improvement in pain relief in patients with knee osteoarthritis relative to immediate-releasetriamcinolone acetonide, the current standard of care. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
RCT Entities:
BACKGROUND:Intra-articular corticosteroids are a mainstay in the treatment of knee osteoarthritis, and in clinical trials, they demonstrate a large initial analgesic effect that wanes over one to four weeks with the rapid efflux of drug from the joint. The present study was undertaken to determine if FX006, an extended-release formulation of triamcinolone acetonide, can provide pain relief that is superior to the current standard of care, immediate-release triamcinolone acetonide. METHODS: In this Phase-2, double-blind, multicenter study, 228 patients with moderate to severe knee osteoarthritis pain were randomized to a single intra-articular injection of FX006 (containing 10, 40, or 60 mg of triamcinolone acetonide) or 40 mg of immediate-release triamcinolone acetonide. Data on the mean daily pain on the 11-point Numeric Rating Scale were collected over twelve weeks; the primary efficacy end point was the change from baseline to each of eight, ten, and twelve weeks in the weekly mean of the mean daily pain intensity scores analyzed with a longitudinal mixed-effects model. RESULTS: The 10-mg dose of FX006 produced pain relief that was improved relative to immediate-release triamcinolone acetonide at two through twelve weeks, although the difference in pain relief was not significant (p ≥ 0.05). The 40-mg dose of FX006 produced pain relief that was improved at two through twelve weeks and was significantly superior to immediate-release triamcinolone acetonide at five to ten weeks (p < 0.05 at each time point). At the 40-mg dose of FX006, prespecified secondary analyses, including responder analyses and all Western Ontario and McMaster Universities subscales, were significantly superior (p < 0.05) to immediate-release triamcinolone acetonide at eight weeks, and the time-weighted mean pain relief (assessed with mean daily pain intensity scores) was significantly superior to immediate-release triamcinolone acetonide over one to twelve weeks (p = 0.04). The 60-mg dose did not provide additional improvement relative to the 40-mg dose. Adverse events were generally mild and similar across all treatments. CONCLUSIONS:Intra-articular injection of FX006, an extended-release formulation of triamcinolone acetonide, provided a clinically relevant improvement in pain relief in patients with knee osteoarthritis relative to immediate-release triamcinolone acetonide, the current standard of care. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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