A novel recombinant anti-cluster of differentiation 20 humanized monoclonal antibody (B001) for the treatment of neuromyelitis optica spectrum disorder: a phase 1, multicenter randomized, double-blind trial

Introduction B001 is a recombinant humanized anti-CD20 monoclonal antibody targeting CD20+ B cells, that has demonstrated superior B cell depletion and anti-proliferative and cytotoxic effects compared to rituximab in a pre-clinical study. The present phase 1b trial assessed the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of B001 in aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (NMOSD). Methods This phase 1b randomized, double-blind, placebo-controlled trial screened 25 NMOSD patients (April 2022–June 2024). Twenty-two patients received intravenous B001 (350, 700 or 1,000 mg) or placebo via a 3 + 3 dose escalation design, randomized 3:1 to active drug or placebo on days 1 and 15. The primary endpoints were the occurrence of dose-limiting toxicity (DLT) and to recommend the dosage for the phase 2 trial. Results Among 22 randomized patients (350 mg: n = 3; 700 mg: n = 8; 1,000 mg: n = 6; placebo: n = 5), 20 (90.9%) completed the study. No DLT occurred in evaluable patients. Treatment-related adverse events (TRAEs) occurred in 7/21 (33.3%) patients, including urinary tract infection (14.3%), infusion-related reactions (9.5%), abnormal blood routine tests (9.5%) and hyperlipidemia (4.8%). No TRAEs led to discontinuation, dose reduction or death. Pharmacokinetic analysis revealed that supra-proportional exposure increased at 1,000 mg vs . 700 mg. Pharmacodynamics showed sustained B cell depletion (nearly 0/μL) for 24 weeks. No NMOSD relapses occurred during the 24-week study. Conclusion B001 demonstrated favorable safety and tolerability, with 700 mg selected as the recommended phase 2 dose. Clinical Trial Registration https://clinicaltrials.gov/study/NCT05145361 , identifier NCT05145361.