An Open-label Study of Povetacicept in Autoantibody-Associated Glomerular Diseases (RUBY-3)

Alpine Immune Sciences

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: Povetacicept

Study type: Interventional

Funder types: Industry

Identifiers

NCT05732402

AIS-D03

Details and patient eligibility

About

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 .

Enrollment: 296 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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296 participants in 1 patient group

Povetacicept

Experimental group

Description:

Participants will receive Povetacicept for 24 weeks with the possibility of participating in treatment extensions through 104 weeks of treatment.

Treatment:

Drug: Povetacicept