2547 Humoral response to COVID vaccine and infection is intact during sibeprenlimab treatment of IgAN: data from the ENVISION trial

Abstract Background and Aims In the Phase 2 placebo-controlled ENVISION trial, the APRIL (A Proliferation Inducing Ligand) inhibitor sibeprenlimab significantly decreased proteinuria and stabilized estimated glomerular filtration rate decline in patients with immunoglobulin A nephropathy (IgAN) [1]. A substudy was conducted to evaluate the humoral response to SARS-CoV-2 mRNA vaccination and infection. Here, we report the unblinded analysis of COVID outcomes in the overall and substudy populations of ENVISION. Method Patients enrolled in ENVISION (NCT04287985) received 12 monthly intravenous infusions of sibeprenlimab (2, 4, or 8 mg/kg) or placebo and were followed for 16 months after the first dose of study drug. Recognized COVID infection (reported as an adverse event [AE]) and vaccination data were recorded for all patients. For patients in the substudy, serum antibody responses to SARS-CoV-2 spike and nucleocapsid proteins were measured monthly using a validated Meso Scale Discovery V-PLEX SARS-CoV-2 Panel 24 multiplex assay. Vaccine responses among those who received a primary two-dose mRNA COVID vaccine series, with no recent or concurrent COVID infection, were evaluated. Peak post-vaccine serum SARS-CoV-2 receptor-binding domain (RBD) immunoglobulin G (IgG) titers were reported in World Health Organization binding antibody units (BAU)/mL. Slopes of RBD IgG decline curves were used to generate estimates of time above a protective threshold of 300 BAU/mL. Welch's two-sample t-test was applied to log-transformed peak RBD titers for significance testing. COVID infection–induced antibody responses and severity of COVID symptoms were also assessed. In substudy patients, retrospective serologic diagnosis of COVID infection was established when simultaneous elevation of nucleocapsid and spike antibody titers, unexplained by vaccine history, was observed. Results Among 155 patients who received sibeprenlimab (n = 117) or placebo (n = 38), 56 (36.1%) had COVID infection reported as an AE during the study (Table 1). Overall, proportionally fewer sibeprenlimab recipients (33.3%) had a reported COVID AE compared with placebo recipients (44.7%). Two patients (one each in the sibeprenlimab and placebo groups) were hospitalized with serious COVID AEs in accordance with local management protocols; none were admitted to intensive care or mechanically ventilated and there were no COVID-related deaths. The majority of COVID AEs were of mild severity, regardless of treat