P1535: SAFETY AND TOLERABILITY OF SINGLE ESCALATING DOSES OF INTRAVENOUS NIPOCALIMAB IN HEALTHY JAPANESE ADULTS: A RANDOMIZED, PHASE 1 PLACEBO-CONTROLLED STUDY

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Background: Autoimmune hemolytic anemia (AIHA) is a rare, life-threatening disorder characterized by the destruction of red blood cells (RBCs) by autoantibodies. In Japan, the estimated prevalence of AIHA is 3-10 cases per 1 million person-years. Of these, approximately 90% of patients present with warm AIHA (wAIHA), which occurs when pathogenic IgG antibodies bind to RBCs at a temperature of ~37 °C. There is currently no approved treatment for wAIHA, and patients with severe symptomatic anemia are generally managed with corticosteroids, immunosuppressants, rescue therapies, and immune cell depleting biologic therapies. Nipocalimab is a fully human, effectorless IgG1 monoclonal antibody in clinical development for wAIHA. Nipocalimab targets the IgG binding site on the neonatal Fc receptor (FcRn) to reduce circulating IgG including anti-RBC autoantibodies. In a prior phase 1 study in healthy adults receiving single and multiple ascending doses administered by intravenous (IV) infusion, nipocalimab was well-tolerated with an adverse event profile comparable to placebo. However, the proportion of Asian participants in that study was small, and therefore the safety of nipocalimab required further investigation in this population. Aims: To assess the safety and tolerability of single escalating doses of nipocalimab administered as IV infusions in healthy Japanese adults. Methods: The trial was a randomized, double-blind, placebo-controlled, escalating single dose study. Eligible participants were healthy Japanese males or females aged 18-64 years with no clinically significant medical or physical conditions. Dosing cohorts were: nipocalimab 10 mg/kg, 30 mg/kg, and 60 mg/kg or matching placebo, infused IV over 30 min. Escalation to the next dose level only proceeded following review of safety and tolerability by the principal investigator. Safety was assessed by the frequency of treatment-emergent adverse events (TEAEs), as well as abnormalities in clinical laboratory assessments, physical examinations, or vital signs. Results: A total of 24 Japanese participants (92% female) were randomized, received study drug, and completed the study. A total of 3 participants (12.5%) experienced 1 or more TEAE: 2 in the 30 mg/kg nipocalimab cohort and 1 in the 60 mg/kg nipocalimab cohort (Table). Mild (grade 1) dizziness was the most common TEAE, which was reported by 2 participants, 1 each in the 30 mg/kg and 60 mg/kg nipocalimab cohorts. Mild influenza-like illness was reported by 1 participant who received 30 mg/kg nipocalimab and mild diarrhea was reported by 1 participant who received 60 mg/kg nipocalimab; these TEAEs were considered by the investigator as unrelated to study drug. One participant in the 30 mg/kg nipocalimab cohort discontinued study drug infusion after 22 minutes due to a moderate infusion-related reaction, which was considered to be related to study treatment. This AE was managed with an antihistamine, and the participant received only 22 mg of nipocalimab. There were no clinically significant changes in laboratory parameters or vital signs, no injection site reactions, serious adverse events, or deaths. Image:Summary/Conclusion: Single doses of nipocalimab, administered at doses between 10 mg/kg and 60 mg/kg by IV infusion, were generally safe and well-tolerated in healthy Japanese adults, consistent with the prior phase 1 study in a general population, which included Asian and non-Asian participants.