Efficacy, safety and tolerability of rozanolixizumab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a randomised, subject-blind, investigator-blind, placebo-controlled, phase 2a trial and open-label extension study

J Neurol Neurosurg Psychiatry. 2024 Aug 16;95(9):845-854. doi: 10.1136/jnnp-2023-333112.

Abstract

Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a peripheral nerve disorder characterised by weakness and sensory loss. We assessed the neonatal Fc receptor inhibitor rozanolixizumab for CIDP management.

Methods: CIDP01 (NCT03861481) was a randomised, subject-blind, investigator-blind, placebo-controlled, phase 2a study. Adults with definite or probable CIDP receiving subcutaneous or intravenous immunoglobulin maintenance therapy were randomised 1:1 to 12 once-weekly subcutaneous infusions of rozanolixizumab 10 mg/kg or placebo, stratified according to previous immunoglobulin administration route. Investigators administering treatment and assessing efficacy, and patients, were blinded. The primary outcome was a change from baseline (CFB) to day 85 in inflammatory Rasch-built Overall Disability Scale (iRODS) score. Eligible patients who completed CIDP01 entered the open-label extension CIDP04 (NCT04051944).

Results: In CIDP01, between 26 March 2019 and 31 March 2021, 34 patients were randomised to rozanolixizumab or placebo (17 (50%) each). No significant difference in CFB to day 85 in iRODS centile score was observed between rozanolixizumab (least squares mean 2.0 (SE 3.2)) and placebo (3.4 (2.6); difference -1.5 (90% CI -7.5 to 4.5)). Overall, 14 (82%) patients receiving rozanolixizumab and 13 (76%) receiving placebo experienced a treatment-emergent adverse event during the treatment period. Across CIDP01 and CIDP04, rozanolixizumab was well tolerated over up to 614 days; no clinically meaningful efficacy results were seen. No deaths occurred.

Conclusions: Rozanolixizumab did not show efficacy in patients with CIDP in this study, although this could be due to a relatively high placebo stability rate. Rozanolixizumab was well tolerated over medium-to-long-term weekly use, with an acceptable safety profile.

Keywords: FC RECEPTOR; MOVEMENT DISORDERS; MYASTHENIA; NEUROMUSCULAR; RANDOMISED TRIALS.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Female
  • Humans
  • Immunoglobulins, Intravenous / adverse effects
  • Immunoglobulins, Intravenous / therapeutic use
  • Male
  • Middle Aged
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating* / drug therapy
  • Single-Blind Method
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • rozanolixizumab
  • Immunoglobulins, Intravenous

Associated data

  • ClinicalTrials.gov/NCT04051944