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

NCT05732402 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: AIS-D03
• Study Type: interventional
• Target: 72
• Locations: 4 countries
• Sites: 30

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

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)

Outcome Measures

Primary Outcomes (2)

• Part A: Safety as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Study Day 1 Through 24 Weeks After Last Dose Of Study Drug

• Part B: Safety as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Study Day 1 Through 12 Weeks After Last Dose Of Study Drug

Secondary Outcomes (21)

• Part A: Incidence and Titer of Anti-drug Antibodies (ADA) Against Povetacicept

  Study Day 1 Through 24 Weeks After Last Dose Of Study Drug

• Part B: Incidence and Titer of Anti-drug Antibodies (ADA) Against Povetacicept

  Study Day 1 Through 12 Weeks After Last Dose Of Study Drug

• Part A: Time Required for Povetacicept To Reach Half its Concentration (t1/2)

  Study Day 1 Through 24 Weeks After Last Dose Of Study Drug

• Part B: Time Required for Povetacicept To Reach Half its Concentration (t1/2)

  Study Day 1 Through 12 Weeks After Last Dose Of Study Drug

• Part A: Change from Baseline in Serum Ig Isotypes (IgM, total IgA, IgA1, IgA2, total IgG, IgG1, IgG2, IgG3, IgG4, IgE).

  Study Day 1 Through 24 Weeks After Last Dose Of Study Drug

Study Arms (1)

Povetacicept

EXPERIMENTAL

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.

Drug: Povetacicept

Interventions

Povetacicept DRUG

Administered by subcutaneous injection every 4 weeks

Also known as: ALPN-303

Povetacicept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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
• AAV

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alpine Immune Sciences, Inc.: lead

Study Sites (30)

Investigational Site (523)

Phoenix, Arizona, 85016, United States

Location

Investigational Site (501)

Phoenix, Arizona, 85302, United States

Location

Investigational Site (524)

Tucson, Arizona, 85712, United States

Location

Investigational Site (506)

Valencia, California, 91335, United States

Location

Investigational Site (513)

Arvada, Colorado, 80002, United States

Location

Investigational Site (512)

Orlando, Florida, 32806, United States

Location

Investigational Site (525)

Tamarac, Florida, 33321, United States

Location

Investigational Site (502)

Lawrenceville, Georgia, 30046, United States

Location

The Johns Hopkins University School of Medicine

Baltimore, Maryland, 21224, United States

Location

Investigational Site (503)

Boston, Massachusetts, 02115, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Investigational Site (509)

Newark, New Jersey, 07103, United States

Location

Investigational Site (511)

Albany, New York, 12209, United States

Location

Investigational Site (508)

Brooklyn, New York, 11203, United States

Location

Investigational Site (518)

Bethlehem, Pennsylvania, 18017, United States

Location

Investigational Site (118)

Colleyville, Texas, 76034, United States

Location

Investigational Site (516)

Houston, Texas, 77054, United States

Location

Investigational Site (526)

Irving, Texas, 75061, United States

Location

Investigational Site (519)

Concord, New South Wales, 2139, Australia

Location

Investigational Site (515)

Saint Albans, Victoria, 3021, Australia

Location

Investigational Site (102)

Nedlands, Western Australia, 6009, Australia

Location

Investigational Site (191)

Caguas, 00725, Puerto Rico

Location

Investigational Site (507)

Cheonan, Chungcheongnam-do, 31151, South Korea

Location

Investigational Site (505)

Anyang-si, Gyeonggi-do, 14068, South Korea

Location

Investigational Site (504)

Goyang-si, Gyeonggi-do, 10444, South Korea

Location

Investigational Site (510)

Guri-si, Gyeonggi-do, 11923, South Korea

Location

Investigational Site (125)

Seoul, Gyeonggi-do, 03080, South Korea

Location

Investigational Site (520)

Seoul, Gyeonggi-do, 03181, South Korea

Location

Investigational Site (521)

Seoul, Gyeonggi-do, 05278, South Korea

Location

Investigational Site (116)

Suwon, Gyeonggi-do, 16499, South Korea

Location

MeSH Terms

Conditions

Lupus Nephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Granulomatosis with Polyangiitis; Churg-Strauss Syndrome

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: February 17, 2023
• Study Start: March 15, 2023
• Primary Completion (Estimated): March 2, 2028
• Study Completion (Estimated): March 2, 2028
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); US (18); AU (3); KR (8)