Fulranumab in Patients With Pain Associated With Postherpetic Neuralgia and Postraumatic Neuropathy: Efficacy, Safety, and Tolerability Results From a Randomized, Double-blind, Placebo-controlled, Phase-2 Study

Clin J Pain. 2017 Feb;33(2):99-108. doi: 10.1097/AJP.0000000000000388.

Abstract

Objective: Fulranumab is an antibody that specifically neutralizes the biological activity of human nerve growth factor. This multicenter, phase-2, randomized, double-blind (DB), placebo-controlled study evaluated the analgesic efficacy and safety of fulranumab in postherpetic neuralgia (PHN) and posttraumatic neuropathy (PTN) patients.

Methods: Patients (18 to 80 y) with inadequately controlled moderate-to-severe pain received study medication (subcutaneous injection) every 4 weeks. PHN patients were randomized (3:2:2:3) to receive either placebo or one of 3 doses of fulranumab: 1 mg (1 mgQ4 wk), 3 mg (3 mgQ4 wk), or 10 mg (10 mgQ4 wk). PTN patients were randomized (1:1) to receive either placebo or fulranumab 10 mgQ4 wk.

Results: The US Food and Drug Administration placed a clinical hold (December 23, 2010) on all trials of antinerve growth factor drugs, including fulranumab, due to identified risks of osteonecrosis or rapidly progressing osteoarthritis; therefore, only 49 (of 150 planned) PHN patients and 34 (of 50 planned) PTN patients completed the DB efficacy evaluation. There was no significant difference (P>0.05, fulranumab vs. placebo) for change in 7-day average of daily pain intensity scores from DB baseline to end of 12-week DB efficacy phase in PHN or PTN patients (primary endpoint). No significant difference was found with fulranumab versus placebo (P>0.05) in other efficacy measures in either PHN or PTN patients. The most common treatment-emergent adverse events (>10% incidence) in PTN patients were sinusitis, carpal tunnel syndrome, and headache, whereas in PHN patients it was arthralgia.

Discussion: Fulranumab did not demonstrate efficacy in either PHN or PTN patients, but was generally well-tolerated in this small underpowered and abbreviated study.

Trial registration: ClinicalTrials.gov NCT00964990.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics / adverse effects
  • Analgesics / blood
  • Analgesics / therapeutic use*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neuralgia, Postherpetic / drug therapy*
  • Pain Measurement
  • Subcutaneous Absorption
  • Treatment Failure
  • Young Adult

Substances

  • Analgesics
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • fulranumab

Associated data

  • ClinicalTrials.gov/NCT00964990