an open-label study of povetacicept in autoantibody-associated glomerular diseases

Conditions: Lupus Nephritis; Immunoglobulin A Nephropathy; Membranous Nephropathy; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Summary: the goal of this clinical study is to evaluate multiple dose levels of povetacicept in adults with immunoglobulin a (iga) nephropathy, membranous nephropathy, lupus-related kidney disease (lupus nephritis). or anti-neutrophil cytoplasmic antibody (anca) associated vasculitis to determine if povetacicept is safe and potentially beneficial in treating these diseases. during the study treatment period, participants will receive povetacicept approximately every 4 weeks for 6 months, with the possibility of participating in a 6-month treatment extension period and an optional 52 week treatment extension period .


Eligibility criteria:
key inclusion criteria summary: 1. biopsy-confirmed autoantibody-associated glomerular disease: immunoglobulin a nephropathy (igan), primary membranous nephropathy (pmn), or lupus nephritis (ln) 2. indication-specific criteria: a. igan * biopsy-confirmed diagnosis less than or equal to (≤)10 years prior to the start of screening and screening upcr greater than or equal to (≥)0.5 g/g. * no background immunosuppression therapies. pmn * a historical biopsy-confirmed diagnosis with positive anti-pla2r1 antibodies or anti-thsd7a antibodies at screening and screening upcr ≥1 g/g * inadequate reduction of proteinuria determined by the principal investigator (pi) despite optimal supportive care for at least 12 weeks. * no background immunosuppression therapies except for optional calcineurin inhibitors. ln * a biopsy-confirmed diagnosis of active, proliferative class iii, iv, (with or without class v) ln ≤6 months prior to the start of screening and * screening upcr ≥1 g/g, * positive anti-dsdna at screening * on stable background immunosuppression ≥ 8 weeks prior to day 1 aav • past diagnosis of renal aav, defined as either of the following: * history of renal biopsy consistent with renal aav. * history of clinically diagnosed renal aav. * myeloperoxidase (mpo)-anca or proteinase 3 (pr3)-anca positive by enzyme-linked immunosorbent assay at screening. * at least 4 weeks since initiation of aav induction therapy, if applicable. 3. on maximal dose or the maximally tolerated dose aceis/arbs for ≥12 weeks prior to study day 1 key exclusion criteria summary: 1. prior diagnosis of, or fulfills diagnostic criteria for, another renal disease 2. egfr \<30 (milliliter per minute per square meter (ml/min/1.73m\^2) or rapidly progressive glomerulonephritis 3. recent serious or ongoing infection; risk or history of serious infection 4. receipt of b cell depleting therapies or anti-baffand/or april therapies within protocol specified timeframes

Keywords: iga nephropathy glomerulonephritis, iga immunoglobulin a nephropathy berger disease lupus nephritis lupus glomerulonephritides primary membranous nephropathy membranous nephropathy glomerulonephritis, membranous pla2r thsd7a alpn-303 povetacicept ruby-3 ruby3 gd-iga1 gdiga1 anti-neutrophil cytoplasmic antibody associated vasculitis (anca) vasculitis aav microscopic polyangiitis granulomatosis with polyangiitis eosinophilic granulomatosis with polyangiitis wegener's granulomatosis churg-strauss disease myeloperoxidase (mpo) proteinase 3 (pr3)