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

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 95; no. 9; pp. 845 - 854
• Main Authors: Querol, Luis, De Sèze, Jérôme, Dysgaard, Tina, Levine, Todd, Rao, T Hemanth, Rivner, Michael, Hartung, Hans-Peter, Kiessling, Peter, Shimizu, Saori, Marmol, Dominika, Bozorg, Ali, Colson, Anny-Odile, Massow, Ute, Eftimov, Filip, Bleecker, Jan De, Claeys, Kristl G, Debien, Elisa, Noordhout, Alain Maertens de, Sommer, Claudia, Garz, Katharina, Stettner, Mark, Schmidt, Jens, Fernández, Nuria Vidal, Gámez, Josep, Segura, Anna Canovas, Morales, Raúl Juntas, Hewamadduma, Channa, Haslam, Liam, Quarles, Brandy, Gable, Karissa
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.09.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antigens; Apheresis; Disease; FC RECEPTOR; Female; Humans; Immunoglobulins; Immunoglobulins, Intravenous - adverse effects; Immunoglobulins, Intravenous - therapeutic use; Male; Middle Aged; MOVEMENT DISORDERS; MYASTHENIA; Neuromuscular; Neuromuscular diseases; Patients; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating - drug therapy; RANDOMISED TRIALS; Single-Blind Method; Treatment Outcome; Tuberculosis; RANDOMISED TRIALS; MOVEMENT DISORDERS; MYASTHENIA; FC RECEPTOR; NEUROMUSCULAR
• ISSN: 0022-3050; 1468-330X; 1468-330X
• DOI: 10.1136/jnnp-2023-333112

BackgroundChronic 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.MethodsCIDP01 (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).ResultsIn 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.ConclusionsRozanolixizumab 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.