Objective. We evaluated in a proof-of-concept double-blind placebo-controlled randomized trial the efficacy and safety of intra-articular sprifermin (recombinant human fibroblast growth factor 18) in patients with symptomatic knee OA. Methods. Sprifermin was evaluated as intra-articular injection at 10, 30, and 100μg. Primary efficacy endpoint was change in central medial femorotibial compartment (cMFTC) cartilage thickness at 6 and 12 months using quantitative MRI (qMRI). Primary safety endpoints were nature, incidence and severity of local and systemic treatment-emergent adverse events, acute inflammatory reactions and laboratory assessments. Secondary endpoints included changes in total and compartment femorotibial cartilage thickness and volume by qMRI, joint space width (JSW) from radiographs, and Western Ontario McMaster Universities (WOMAC) pain. Results. 192 patients were randomized and evaluated for safety, 180 completed the trial, 168 evaluated for primary efficacy endpoint. We found no statistically significant dose-response in change in cMFTC 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 improved in WOMAC pain, with statistically significant less improvement at 12 months in patients receiving 100μg sprifermin than placebo. There was no significant difference in SAEs, TEAEs, AIRs between sprifermin and placebo groups. Conclusion. There was no statistically significant relationship between treatment group and reduction in cMFTC cartilage thickness. However, pre-specified structural secondary endpoints showed statistically significant dose-dependent reductions following sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns. Clinicaltrials.gov identification: NCT01033994. © 2014 American College of Rheumatology.
Subject classification (UKÄ)
- Rheumatology and Autoimmunity