A Randomized Trial Evaluating Various Administration Routes of Natalizumab in Multiple Sclerosis. (3rd March 2016) - Plavina, Tatiana
Abstract: The study's primary objective was to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of single subcutaneous (SC) or intramuscular (IM) 300‐mg doses of natalizumab with IV 300‐mg doses of natalizumab in patients with multiple sclerosis (MS). Secondary objectives included investigation of the safety, tolerability, and immunogenicity of repeated SC and IM natalizumab doses. DELIVER was a 32‐week, open‐label, multicenter study of natalizumab‐naive patients with relapsing‐remitting MS (RRMS) or secondary progressive MS (SPMS) randomized to receive 300 mg natalizumab by SC injection, IM injection, or IV infusion. PK and PD were evaluated over 8 weeks after the first natalizumab treatment (Part 1) and over 24 weeks with repeated dosing every 4 weeks, beginning at week 8 (Part 2). Seventy‐six patients (24 with RRMS and 52 with SPMS) were enrolled in DELIVER. Following SC or IM administration of natalizumab, peak serum concentrations were approximately 40% of those observed with IV administration and showed no major differences in elimination characteristics. Mean bioavailability relative to IV administration was 57.1% to 71.3% with SC administration and 48.7% with IM administration; mean trough serum concentrations were similar with SC or IV administration and lower with IM administration. Following single or multiple doses of natalizumab, PD response was comparable across administration routes and disease stages. No meaningful differences were observed across administration groups in the incidence or nature of overall adverse events, serious adverse events, administration site reactions, hypersensitivity reactions, or antinatalizumab antibodies. These findings support the comparability of PD measures of natalizumab administered IV, SC, or IM.