An Open-label Study of Povetacicept (ALPN-303) in Autoimmune Kidney Diseases

Overview

The goal of this clinical study is to evaluate multiple dose levels of povetacicept (ALPN-303) 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

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:
   1. IgAN
      • Biopsy-confirmed diagnosis ≤10 years prior to the start of screening AND Screening UPCR ≥0.5 g/g.
      • No background immunosuppression therapies.
   2. 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 mL/min/1.73m2 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-BAFF/APRIL therapies within protocol specified timeframes