Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Immunoglobulin A Nephropathy, Lupus Nephritis, Membranous Nephropathy
Conditions
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)
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.
Interventions
DRUGPovetacicept
Administered by subcutaneous injection every 4 weeks
Sponsors
Alpine Immune Sciences, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Part B: Change from Baseline in Serum Ig Isotypes (IgM, total IgA, IgA1, IgA2, total IgG, IgG1, IgG2, IgG3, IgG4, IgE) | Study Day 1 Through 12 Weeks After Last Dose Of Study Drug |
| Part A: Change from Baseline in Peripheral Blood Lymphocytes and Subsets | Study Day 1 Through 24 Weeks After Last Dose Of Study Drug |
| Part B: Change from Baseline in Peripheral Blood Lymphocytes and Subsets | 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 | Study Day 1 Through 24 Weeks After Last 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) | Baseline and at Week 24 |
| Part A: Change From Baseline Over Time In Complement Components (C3, C4, CH50) | 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) | Study Day 1 Through 12 Weeks After Last Dose Of Study Drug |
| Part A: Immunological Remission (pMN only) | Study Day 1 Through Week 24 After Dose of Study Drug |
| Part B: Immunological Remission (pMN only) | Study Day 1 Through Week 12 After Dose of Study Drug |
| Part B: Change from Baseline at Week 24 in Estimated Glomerular Filtration Rate (eGFR) | Baseline and at Week 24 |
| Part A: Renal Response | At Week 24 |
| Part A: Remission of Vasculitis (Birmingham Vasculitis Activity Score (BVAS = 0)) (for AAV cohorts only) | At Week 24 |
| Part A: Changes in Biomarkers Including Cytokines and Autoantibodies After Treatment with Povetacicept | 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 | Study Day 1 Through 12 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 | Study Day 1 Through 12 Weeks After Last Dose Of Study Drug |
| Part A: Change from Baseline at Week 24 in Estimated Glomerular Filtration Rate (eGFR) | Baseline and at Week 24 |
Countries
Australia, Puerto Rico, South Korea, United States
Outcome results
None listed