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

Phase 2Active Not RecruitingNCT05732402

Alpine Immune Sciences, Inc.72 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria Summary: 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. Key Exclusion Criteria Summary: 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. Other protocol defined Inclusion/Exclusion criteria will apply

Outcomes

Primary Outcomes

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

Time frame: 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)

Time frame: Study Day 1 Through 12 Weeks After Last Dose Of Study Drug

Secondary Outcomes

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

Time frame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug

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

Time frame: 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)

Time frame: 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)

Time frame: 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).

Time frame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug

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

Time frame: Study Day 1 Through 12 Weeks After Last Dose Of Study Drug

Part A: Change from Baseline in Peripheral Blood Lymphocytes and Subsets

Time frame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug

Part B: Change from Baseline in Peripheral Blood Lymphocytes and Subsets

Time frame: Study Day 1 Through 12 Weeks After Last Dose Of Study Drug

Part A:Change from Baseline Over Time In Circulating Levels Of anti-dsDNA in LN; galactose deficient IgA1 (Gd-IgA1) and anti-Gd-IgA1 in IgAN; anti-PLA2R1 or anti THSD7A in pMN and anti-PR3 or anti-MPO in AAV

Time frame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug

Part B: Change from Baseline Over Time In Circulating Levels Of galactose deficient IgA1 (Gd-IgA1) and anti-Gd-IgA1 in IgAN; anti-PLA2R1 or anti THSD7A in pMN

Time frame: Study Day 1 Through 12 Weeks After Last Dose Of Study Drug

Part A: Change From Baseline Over Time In Complement Components (C3, C4, CH50)

Time frame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug

Part B: Change From Baseline Over Time In Complement Components (C3, C4, CH50)

Time frame: Study Day 1 Through 12 Weeks After Last Dose Of Study Drug

Part A: Immunological Remission (pMN only)

Time frame: Study Day 1 Through Week 24 After Dose of Study Drug

Part B: Immunological Remission (pMN only)

Time frame: Study Day 1 Through Week 12 After Dose of Study Drug

Part A: Change from Baseline at Week 24 in UPCR (Urine protein/creatinine ratio) (based on assessment of 24-hour urine)

Time frame: Baseline and at Week 24

Part A: Change from Baseline at Week 24 in Estimated Glomerular Filtration Rate (eGFR)

Time frame: Baseline and at Week 24

Part B: Change from Baseline at Week 24 in Estimated Glomerular Filtration Rate (eGFR)

Time frame: Baseline and at Week 24

Part A: Renal Response

Time frame: At Week 24

Part A: Remission of Vasculitis (Birmingham Vasculitis Activity Score (BVAS = 0)) (for AAV cohorts only)

Time frame: At Week 24

Part A: Changes in Biomarkers Including Cytokines and Autoantibodies After Treatment with Povetacicept

Time frame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug

Part B: Changes in Biomarkers Including Cytokines and Autoantibodies After Treatment with Povetacicept

Time frame: Study Day 1 Through 12 Weeks After Last Dose Of Study Drug

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

Overview

Conditions

Interventions

Eligibility

Locations (30)

Outcomes

Primary Outcomes

Secondary Outcomes