Wang H.,U.S. National Institutes of Health |
Romano G.,Janssen Research and DevelopmentNJ |
Frustaci M.E.,Janssen Research and DevelopmentNJ |
Bohidar N.,Janssen Research and DevelopmentNJ |
And 7 more authors.
Neurology | Year: 2014
Objective: To assess efficacy and safety of fulranumab, a fully human monoclonal antibody against nerve growth factor, in patients with diabetic peripheral neuropathic pain (DPNP). Methods: In this phase II, double-blind, placebo-controlled trial, patients with moderate to severe DPNP were randomized to treatments with fulranumab (1, 3, or 10 mg) or placebo administered subcutaneously every 4 weeks. Results: Because of early study termination (clinical hold) by the US Food and Drug Administration, 77 (intent-to-treat) of the planned 200 patients were enrolled. The primary endpoint, the mean reduction of average daily pain at week 12 compared with baseline, showed a positive dose-response relationship (p 5 0.014, 1-sided); the pair-wise comparison between the 10-mg group and placebo was significant (unadjusted p 5 0.040, 2-sided). An exploratory responder analysis revealed that a greater proportion of patients in the 10-mg group reported ≥30%reduction in the average DPNP intensity compared with placebo at week 12 (p 5 0.006). Although not statistically significant, several secondary endpoints showed directionally similar results to the primary efficacy dose-response relationship. During the combined efficacy and safety extension phases, the top 3 treatment-emergent adverse events in the combined fulranumab group were arthralgia (11%), edema peripheral (11%), and diarrhea (9%). No cases of joint replacement or death were reported. Conclusion: Despite early study termination, fulranumab treatment resulted in dose-dependent efficacy and was generally well tolerated. Classification of evidence: This study provides Class I evidence that in patients with DPNP, fulranumab 10 mg reduces pain by 1.2 points on an 11-point scale compared with placebo. © 2014 American Academy of Neurology.