Design of a randomized, placebo-controlled, phase 2 study evaluating the safety and efficacy of tanezumab for treatment of schwannomatosis-related pain

Contemp Clin Trials. 2022 Oct:121:106900. doi: 10.1016/j.cct.2022.106900. Epub 2022 Aug 26.


Background: Schwannomatosis (SWN) is a rare tumor suppressor syndrome that predisposes affected individuals to develop multiple schwannomas and, less often, meningiomas. The most common symptom is chronic, severe pain. No medications are broadly effective in treating SWN-associated pain. The clinical trial described in this manuscript is a phase 2, randomized, double-blind, placebo-controlled study investigating the safety and efficacy of tanezumab - a humanized monoclonal antibody that inhibits nerve growth factor - for treatment of SWN-related pain. As the first therapeutic trial for SWN-related pain, it also aims to evaluate trial endpoints, understand recruitment patterns, and improve clinical trial design in this rare disease.

Aims: The primary objective of this trial is to assess the analgesic efficacy of subcutaneous tanezumab 10 mg in subjects with SWN who continue pre-existing pain therapy (excluding non-steroidal anti-inflammatory drugs). The secondary objective is to assess safety in this population. Exploratory objectives include assessment of pain features, quality of life, and predictive biomarkers.

Methods: The study is comprised of four periods (pre-treatment, double-blind treatment, single-arm treatment, safety follow-up) across 10 months with a delayed-start trial design to allow all participants to receive tanezumab. Forty-six participants will be enrolled and randomized 1:1 to receive either tanezumab or placebo subcutaneously in the double-blind treatment period; all participants receive tanezumab during the single-arm treatment period.

Conclusions: This study is the first therapeutic trial for SWN patients and targets a biological driver of SWN-related pain. It aims to establish a model for future pain studies in SWN and other rare diseases.

Clinical trial registration: NCT04163419 on

Keywords: Clinical trial design; Clinical trial recruitment; Nerve growth factor; Pain; Schwannomatosis; Tanezumab.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Chronic Pain* / drug therapy
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Humans
  • Neurilemmoma* / complications
  • Neurilemmoma* / drug therapy
  • Neurofibromatoses
  • Osteoarthritis, Knee* / complications
  • Pain Measurement
  • Quality of Life
  • Skin Neoplasms
  • Treatment Outcome


  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal, Humanized
  • tanezumab

Supplementary concepts

  • Schwannomatosis

Associated data