• Hao Wang, Gary Romano, Mary Ellen Frustaci, Norm Bohidar, Huizhong Ma, Panna Sanga, Seth Ness, Lucille J Russell, Margaret Fedgchin, Kathleen M Kelly, and John Thipphawong.
• From the National Institute of Neurological Disorders and Stroke (H.W.), Bethesda, MD; and Janssen Research & Development, LLC (G.R., M.E.F., N.B., H.M., P.S., S.N., L.J.R., M.F., K.M.K., J.T.), NJ. wangh16@ninds.nih.gov.
• Neurology. 2014 Aug 12;83(7):628-37.

ObjectiveTo assess efficacy and safety of fulranumab, a fully human monoclonal antibody against nerve growth factor, in patients with diabetic peripheral neuropathic pain (DPNP).MethodsIn 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.ResultsBecause 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 = 0.014, 1-sided); the pair-wise comparison between the 10-mg group and placebo was significant (unadjusted p = 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 = 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.ConclusionDespite early study termination, fulranumab treatment resulted in dose-dependent efficacy and was generally well tolerated.Classification Of EvidenceThis 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.

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