A PHASE 1 PLACEBO-CONTROLLED SINGLE-DOSE STUDY OF NIPOCALIMAB ADMINISTERED AT DIFFERENT RATES OF INTRAVENOUS INFUSION IN HEALTHY ADULTS

Abstract

Warm autoimmune hemolytic anemia (wAIHA) is a rare, life-threatening disorder characterized by the destruction of red blood cells by pathogenic IgG autoantibodies. There is currently no approved treatment for wAIHA. Nipocalimab is a fully human, aglycosylated, effectorless IgG1 monoclonal antibody that blocks the IgG binding site on the neonatal Fc receptor (FcRn) with high affinity, which is in clinical development for the treatment of wAIHA. In a prior phase 1 study in healthy adults receiving single and multiple ascending doses infused intravenously (IV) over 2 hours, nipocalimab was well-tolerated with an adverse event profile comparable to placebo. However, shorter durations of nipocalimab infusion may be more convenient for patients. Here we assess the safety and tolerability of single doses of nipocalimab administered at different IV infusion rates in healthy adults to support the potential use of shortened infusions in future studies. The trial was a single dose, sequential, randomized, double-blind, placebo-controlled, escalating dose and infusion rate study. Eligible participants were males or females aged 18-55 years with no clinically significant medical or physical conditions. Participants were randomized to 1 of 5 cohorts (n = 8 per cohort [6 nipocalimab, 2 placebo]) to receive nipocalimab 30 mg/kg IV infused over 60, 30, 15 or 7.5 min (0.5, 1, 2, or 4 mg/kg/min), nipocalimab 60 mg/kg IV infused over 15 min (4 mg/kg/min) or matching placebo. Escalation to the next dose level was permitted following review by a safety monitoring committee. Safety was assessed by the frequency and nature of treatment-emergent adverse events (TEAEs). A total of 40 participants (70% female, 93% white) received study drug and were included in the safety analysis; 39 completed the study. A total of 12 participants (40%) experienced TEAEs across all nipocalimab dosing cohorts and 1 (10%) participant experienced TEAEs following administration of placebo. The most frequently reported TEAE was headache, reported by 6 participants with nipocalimab and 1 participant with placebo. Nausea was reported by 3 participants receiving nipocalimab. Grade 2 injection site reactions were reported by 2 participants but were considered unrelated to the investigational agent. None of the TEAEs were severe, and no participants discontinued treatment due to TEAEs; there were no serious adverse events or deaths. Only 4 participants experienced AEs that occurred within 24 hours after the infusion that were considered related to the study drug. Lower rates of nipocalimab infusion were associated with fewer TEAEs, while participants receiving 4 mg/kg/min (as either 30 mg/kg infused over 7.5 min or 60 mg/kg infused over 15 min) reported more TEAEs. Single doses of nipocalimab, when administered at doses up to 60 mg/kg and infusion rates up to 4 mg/kg/min were safe and well-tolerated in healthy adults. The frequency of reported TEAEs was lower in participants receiving IV nipocalimab at rates of 1 or 2 mg/kg/min, providing a target infusion rate for current and future studies. JHL, AV, LEL are employees of Janssen Research & Development, LLC, and AMBP is an employee of Janssen Latin America, which are a wholly owned subsidiaries of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson.