An Open-label Study of Povetacicept in Autoantibody-Associated Glomerular Diseases

NCT ID: NCT05732402

Last Updated: 2025-10-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-15
• Study Completion Date: 2028-03-02

Brief Summary

The goal of this clinical study is to evaluate multiple dose levels of povetacicept in adults with immunoglobulin A (IgA) nephropathy (IgAN), primary membranous nephropathy (pMN), lupus-related kidney disease (lupus nephritis - LN), or anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) 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. Participants with IgAN and pMN may also receive povetacicept for an additional 52 weeks, if eligible.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Povetacicept

Part A: Participants will receive povetacicept for 24 weeks with the possibility of participating in treatment extensions through 104 weeks of treatment.

Part B: Participants with IgAN and pMN will receive povetacicept for an additional 52 weeks.

Group Type: EXPERIMENTAL

Povetacicept

Intervention Type: DRUG

Administered by subcutaneous injection every 4 weeks

Interventions

Povetacicept

Administered by subcutaneous injection every 4 weeks

Intervention Type: DRUG

Other Intervention Names

ALPN-303

Eligibility Criteria

Inclusion Criteria

Part A:

• Biopsy-confirmed autoantibody-associated glomerular disease: immunoglobulin A nephropathy (IgAN), primary membranous nephropathy (pMN), or lupus nephritis (LN)
• On maximal dose or the maximally tolerated dose ACEis/ARBs for ≥12 weeks prior to study Day 1
• Indication-specific criteria:

1. 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.

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.

3. 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,
• Anti-dsDNA at screening. Anti-dsDNA testing is required but the result need not be positive.
• On stable background immunosuppression ≥ 8 weeks prior to Day 1

4. 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.

Part B:

• Participants meet at least 1 of the following criteria:

• Completed investigational product (IP) treatment and 24 weeks of follow-up in Part A, or
• Had IP interruption(s) in Part A, but did not permanently discontinue IP, and completed study visits up to the last scheduled visit of the follow-up period of Part A.

Exclusion Criteria

Part A:

• Prior diagnosis of, or fulfills diagnostic criteria for, another renal disease
• eGFR <30 milliliter per minute per square meter (mL/min/1.73m^2) or rapidly progressive glomerulonephritis
• Recent serious or ongoing infection; risk or history of serious infection
• Receipt of B cell depleting therapies or anti-BAFF and/or APRIL therapies within protocol specified timeframes

Part B:

• History of poor compliance with IP and/or procedures in Part A, as deemed by the investigator or Sponsor
• History of any AEs or clinical conditions during Part A or emerging thereafter that may pose a safety concern for participation in Part B as deemed by investigator or Sponsor.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alpine Immune Sciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Investigational Site (523)

Phoenix, Arizona, United States

Investigational Site (501)

Phoenix, Arizona, United States

Investigational Site (524)

Tucson, Arizona, United States

Investigational Site (506)

Valencia, California, United States

Investigational Site (513)

Arvada, Colorado, United States

Investigational Site (512)

Orlando, Florida, United States

Investigational Site (525)

Tamarac, Florida, United States

Investigational Site (502)

Lawrenceville, Georgia, United States

The Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Investigational Site (503)

Boston, Massachusetts, United States

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Investigational Site (509)

Newark, New Jersey, United States

Investigational Site (511)

Albany, New York, United States

Investigational Site (508)

Brooklyn, New York, United States

Investigational Site (518)

Bethlehem, Pennsylvania, United States

Investigational Site (118)

Colleyville, Texas, United States

Investigational Site (516)

Houston, Texas, United States

Investigational Site (526)

Irving, Texas, United States

Investigational Site (519)

Concord, New South Wales, Australia

Investigational Site (515)

Saint Albans, Victoria, Australia

Investigational Site (102)

Nedlands, Western Australia, Australia

Investigational Site (191)

Caguas, , Puerto Rico

Investigational Site (507)

Cheonan, Chungcheongnam-do, South Korea

Investigational Site (505)

Anyang-si, Gyeonggi-do, South Korea

Investigational Site (504)

Goyang-si, Gyeonggi-do, South Korea

Investigational Site (510)

Guri-si, Gyeonggi-do, South Korea

Investigational Site (125)

Seoul, Gyeonggi-do, South Korea

Investigational Site (520)

Seoul, Gyeonggi-do, South Korea

Investigational Site (521)

Seoul, Gyeonggi-do, South Korea

Investigational Site (116)

Suwon, Gyeonggi-do, South Korea

Countries

United States; Australia; Puerto Rico; South Korea

Other Identifiers

AIS-D03

Identifier Type: -

Identifier Source: org_study_id