Osteoarthritis
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)

https://doi.org/10.1016/j.semarthrit.2009.04.001Get rights and content

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 (<1%) subject in the IA-SA group and 2 (1%) in the IA-BioHA group.

Conclusions

IA-BioHA therapy resulted in significant OA knee pain relief at 26 weeks compared with IA-SA. Subjects treated with IA-BioHA also experienced significant improvements in joint function, treatment satisfaction, and HRQoL.

Section snippets

Subjects and Methods

The study was conducted in the United States from October 2006 to May 2008 in accordance with the International Conference on Harmonization Guidelines for Good Clinical Practice and the Declaration of Helsinki concerning medical research in humans. Subjects were enrolled at 36 sites. Criteria for inclusion were as follows: OA of the knee by American College of Rheumatology criteria (18); moderate to severe pain score of 41 to 90 mm recorded on 100-mm visual analog scale (VAS) immediately

Results

Subject disposition is reflected in Figure 1. To randomize 588 subjects (IA-BioHA n = 293, IA-SA = 295), 821 were screened. Overall, there was an 88% completion rate in each treatment group. There were no differences in demographics between those completing and those discontinuing the study. There were 34 discontinuations in each group. AE discontinuations included 6 in the IA-SA group and 11 in the IA-BioHA group. Protocol violations caused discontinuation in 6 (3 in each group). Two subjects

Discussion

Treatment with IA-BioHA was superior to IA-SA in reducing knee pain due to OA at 26 weeks. Secondary measurements were generally supportive of the primary outcome measurement. IA-BioHA was well tolerated, with no joint effusions.

It is of interest that 6 months following the series of 3 IA-BioHA injections, almost half (47%) the subjects were pain free (100-mm VAS of <20 mm based on 50-foot walk). This compares favorably with 39% pain free with IA-SA. The OARSI responder criteria require a 50%

References (36)

  • Prevalence of disabilities and associated health conditions among adults: United States, 1999

    MMWR Morb Mortal Wkly Rep

    (2001)
  • L. Freifeld

    Who is your customer?

    License! June

    (2005)
  • Population projections. 2004

  • D.D. Waddell

    Viscosupplementation with hyaluronans for osteoarthritis of the knee: clinical efficacy and economic implications

    Drugs Aging

    (2007)
  • C.M. McKee et al.

    Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophagesThe role of HA size and CD44

    J Clin Invest

    (1996)
  • D. Jiang et al.

    Regulation of lung injury and repair by Toll-like receptors with hyaluronan

    Nat Med

    (2005)
  • R.A. Ottaviani et al.

    Inflammatory and immunological responses to hyaluronan preparationsStudy of a murine biocompatibility model

    J Bone Joint Surg

    (2007)
  • S. Gotoh et al.

    [Experimental knee pain model in rats and analgesic effect of sodium hyaluronate (SPH)]

    Nippon Yakurigaku Zasshi

    (1998)
  • Cited by (0)

    This study was supported by Ferring Pharmaceuticals Inc., Parsippany, New Jersey.

    View full text