A Double-Blind, Randomized, Saline-Controlled Study of the Efficacy and Safety of EUFLEXXA® for Treatment of Painful Osteoarthritis of the Knee, With an Open-Label Safety Extension (The FLEXX Trial)

• Published in: Seminars in arthritis and rheumatism 2009-08, Vol.39 (1), p.1-9
• Main Authors: Altman, Roy D., MD, Rosen, Jeffrey E., MD, Bloch, Daniel A., PhD, Hatoum, Hind T., PhD, Korner, Paul, MD, MBA
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; Adjuvants, Immunologic - therapeutic use; Aged; Arthralgia - etiology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; hyaluronate; hyaluronic acid; Hyaluronic Acid - administration & dosage; Hyaluronic Acid - adverse effects; Hyaluronic Acid - therapeutic use; Injections, Intra-Articular; intra-articular therapy; knee; Male; Medical sciences; Middle Aged; Miscellaneous. Osteoarticular involvement in other diseases; Molecular Weight; Osteoarthritis; Osteoarthritis, Knee - complications; Osteoarthritis, Knee - drug therapy; Osteoarthritis, Knee - physiopathology; Outcome Assessment (Health Care); Pain Measurement; Pharmacology. Drug treatments; Quality of Life; Rheumatology; therapy; Treatment Outcome; United States; Walking - physiology
• ISSN: 0049-0172; 1532-866X
• DOI: 10.1016/j.semarthrit.2009.04.001

Objective To report the FLEXX trial, the first well-controlled study assessing the safety and efficacy of Euflexxa (1% sodium hyaluronate; IA-BioHA) therapy for knee osteoarthritis (OA) at 26 weeks. Methods This was a randomized, double-blind, multicenter, saline-controlled study. Subjects with chronic knee OA were randomized to 3 weekly intra-articular (IA) injections of either buffered saline (IA-SA) or IA-BioHA (20 mg/2 ml). The primary efficacy outcome was subject recorded difference in least-squares means between IA-BioHA and IA-SA in subjects' change from baseline to week 26 following a 50-foot walk test, measured via 100-mm visual analog scale (VAS). Secondary outcome measures included Osteoarthritis Research Society International responder index, Western Ontario McMaster University Osteoarthritis Index VA 3.1 subscales, patient global assessment, rescue medication, and health-related quality of life (HRQoL) by the SF-36. Safety was assessed by monitoring and reporting vital signs, physical examination of the target knee following injection, adverse events, and concomitant medications. Results Five hundred eighty-eight subjects were randomized to either IA-BioHA ( n = 293) or IA-SA ( n = 295), with an 88% 26 week completion rate. No statistical differences were noted between the treatment groups at baseline. In the IA-BioHA group, mean VAS scores decreased by 25.7 mm, compared with 18.5 mm in the IA-SA group. This corresponded to a median reduction of 53% from baseline for IA-BioHA and a 38% reduction for IA-SA. The difference in least-squares means was −6.6 mm ( P = 0.002). Secondary outcome measures were consistent with significant improvement in Osteoarthritis Research Society International responder index, HRQoL, and function. Both IA-SA and IA-BioHA injections were well tolerated, with a low incidence of adverse events that were equally distributed between groups. Injection-site reactions were reported by 1 (