Efficacy, Safety, and Pharmacokinetics of Natalizumab in Japanese Multiple Sclerosis Patients: A Double-blind, Randomized Controlled Trial and Open-label Pharmacokinetic Study

Abstract Background Natalizumab, an anti-α4 integrin monoclonal antibody, has demonstrated efficacy in phase 2 and 3 studies of predominantly Caucasian patients with relapsing-remitting multiple sclerosis (RRMS). Objective To evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of natalizumab in Japanese RRMS patients. Methods This multicenter, phase 2 study included an open-label PK/PD study in 12 patients (part A) and a double-blind, placebo-controlled, randomized (computer-generated sequence) study in 94 patients (part B). For part B, patients received intravenous natalizumab 300 mg (n = 47) or placebo (n = 47) every 4 weeks. The primary efficacy endpoint was the rate of development of new active lesions (gadolinium-enhancing or new/enlarging T2 lesions) over 24 weeks. Clinical relapses and safety were also assessed. Results New active lesions developed at a significantly lower mean rate in natalizumab-treated patients (0.06 lesions/24 weeks) than in placebo-treated patients (0.35 lesions/24 weeks) ( p