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J Bone Joint Surg Am. 2018 Apr 18;100(8):666-677. doi: 10.2106/JBJS.17.00154.

Effects of a Single Intra-Articular Injection of a Microsphere Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study.

Author information

1
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom.
2
NIHR Leeds Biomedical Research Centre, Leeds, United Kingdom.
3
Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia.
4
Department of Rheumatology, Metroplex Clinical Research Center, Dallas, Texas.
5
Department of Rheumatology and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina.
6
Department of Rheumatology, Sorbonne Université, INSERM, AP-HP hôpital Saint-Antoine, DHU i2B, Paris, France.
7
Keck School of Medicine, University of Southern California, Los Angeles, California.
8
Ochsner Sports Medicine Institute, New Orleans, Louisiana.
9
Department of Orthopaedic Surgery, Cedars-Sinai Orthopaedic Center, Los Angeles, California.
10
Department of Orthopaedics, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
11
Analgesic Solutions, Natick, Massachusetts.
12
Department of Anesthesia, Tufts University School of Medicine, Boston, Massachusetts.
13
School of Pharmacy, University of Connecticut, Storrs, Connecticut.
14
Clinical Operations (J.L.) and Clinical Research and Medical Affairs (N.B.), Flexion Therapeutics, Inc., Burlington, Massachusetts.
15
Biostatistics, Summit Analytical, LLC, Cary, North Carolina.

Abstract

BACKGROUND:

Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs.

METHODS:

In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit.

RESULTS:

The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: -3.12 versus -2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments.

CONCLUSIONS:

FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point).

LEVEL OF EVIDENCE:

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

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