Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Trial

Authors

  • L. Stefan Lohmander,

    Corresponding author
    1. Lund University, Lund, Sweden
    2. University of Southern Denmark, Odense, Denmark
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    • Dr. Lohmander has received consulting fees, speaking fees, and/or honoraria from Merck Serono, Flexion, Össur, and Servier (less than $10,000 each).

  • Scarlett Hellot,

    1. Merck Serono, Geneva, Switzerland
    Current affiliation:
    1. SEA Stats Consulting, Gaillard, France
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  • Don Dreher,

    1. Totzke & Dreher Scientific, Geneva, Switzerland
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    • Dr. Dreher has received consulting fees from Merck Serono, Actelion, Novartis, and Vifor Pharma (more than $10,000 each), and is a former employee of Merck Serono, Geneva, Switzerland.

  • Eduard F. W. Krantz,

    1. Farmovs-Parexel, Bloemfontein, South Africa
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    • Dr. Krantz has previously served as a principal investigator in studies conducted for Merck Serono.

  • Dawie S. Kruger,

    1. Parexel Early Phase, George, South Africa
    Current affiliation:
    1. GVI Oncology, George, South Africa
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    • Dr. Kruger has previously served as a principal investigator in studies conducted for Merck Serono.

  • Ali Guermazi,

    1. Boston University School of Medicine and Boston Imaging Core Lab, Boston, Massachusetts
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    • Dr. Guermazi has received consulting fees from Merck Serono, Sanofi Aventis, and TissueGene (less than $10,000 each).

  • Felix Eckstein

    1. Paracelsus Medical University, Salzburg, Austria
    2. Chondrometrics, Ainring, Germany
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    • Dr. Eckstein has received consulting fees from AbbVie (less than $10,000) and Merck Serono and Sanofi-Aventis (more than $10,000 each) and has received honoraria from Medtronic and Synthes (less than $10,000 each).

    • Dr. Eckstein also has received research grants from Merck Serono, Novartis, Stryker, Pfizer, GlaxoSmithKline, Eli Lilly, Wyeth, Centocor, Kolon, and Synarc.


Abstract

Objective

To evaluate the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA).

Methods

The study was a randomized, double-blind, placebo-controlled, proof-of-concept trial. Intraarticular sprifermin was evaluated at doses of 10 μg, 30 μg, and 100 μg. The primary efficacy end point was change in central medial femorotibial compartment cartilage thickness at 6 months and 12 months as determined using quantitative magnetic resonance imaging (qMRI). The primary safety end points were nature, incidence, and severity of local and systemic treatment-emergent adverse events (AEs) and acute inflammatory reactions, as well as results of laboratory assessments. Secondary end points included changes in total and compartment femorotibial cartilage thickness and volume as assessed by qMRI, changes in joint space width (JSW) seen on radiographs, and pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results

One hundred ninety-two patients were randomized and evaluated for safety, 180 completed the trial, and 168 were evaluated for the primary efficacy end point. We found no statistically significant dose response in change in central medial femorotibial compartment cartilage thickness. Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume and in JSW narrowing in the lateral femorotibial compartment. All groups had improved WOMAC pain scores, with statistically significantly less improvement at 12 months in patients receiving the 100-μg dose of sprifermin as compared with those receiving placebo. There was no significant difference in serious AEs, treatment-emergent AEs, or acute inflammatory reactions between sprifermin and placebo groups.

Conclusion

No statistically significant relationship between treatment group and reduction in central medial femorotibial compartment cartilage thickness was observed; however, prespecified structural secondary end points showed statistically significant dose-dependent reductions after sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns.

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