title: Fulranumab for treatment of diabetic peripheral neuropathic pain: A randomized controlled trial.
abstract: 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 = 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.
  
  
  CONCLUSIONS
  Despite early study termination, fulranumab treatment resulted in dose-dependent efficacy and was generally well tolerated.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Gary
authors.initials: G
authors.lastname: Romano
authors.affiliation: 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.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Frustaci
authors.affiliation: 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.
authors.forename: Norm
authors.initials: N
authors.lastname: Bohidar
authors.affiliation: 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.
authors.forename: Huizhong
authors.initials: H
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Panna
authors.initials: P
authors.lastname: Sanga
authors.affiliation: 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.
authors.forename: Seth
authors.initials: S
authors.lastname: Ness
authors.affiliation: 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.
authors.forename: Lucille J
authors.initials: LJ
authors.lastname: Russell
authors.affiliation: 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.
authors.forename: Margaret
authors.initials: M
authors.lastname: Fedgchin
authors.affiliation: 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.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Kelly
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Thipphawong
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003929:Diabetic Neuropathies / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000628:therapy*; D059408:Pain Management; D010147:Pain Measurement; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; C000592179:fulranumab