An Open-label Study of Povetacicept (ALPN-303) in Autoimmune Kidney Diseases

Study Overview
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Brief Summary
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The goal of this clinical study is to evaluate multiple dose levels of povetacicept (ALPN-303) in adults with immunoglobulin A (IgA) nephropathy, membranous nephropathy, or lupus-related kidney disease (lupus nephritis) 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 study treatment extension period.

Official Title
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An Open-Label, Multiple-Ascending Dose Study to Assess the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Different Dose Levels of Povetacicept in Subjects With Autoantibody-Associated Glomerular Diseases (RUBY-3)

Conditions
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Lupus Nephritis, Immunoglobulin A Nephropathy, Membranous Nephropathy

Intervention / Treatment
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* Drug: povetacicept
* Drug: povetacicept


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Summary: Biopsy-confirmed autoantibody-associated glomerular disease: immunoglobulin A nephropathy (IgAN), primary membranous nephropathy (pMN), or lupus nephritis (LN) Indication-specific criteria: IgAN Biopsy-confirmed diagnosis ≤10 years prior to the start of screening AND Screening UPCR ≥0.5 g/g. No background immunosuppression therapies. pMN A biopsy-confirmed diagnosis with positive anti-PLA2R1 antibodies or anti-THSD7A antibodies at screening or within 12 weeks prior to the start of screening AND Screening UPCR ≥1 g/g OR A biopsy-confirmed diagnosis ≤5 years prior to the start of screening with both serum and tissue negative for anti-PLA2R1 and anti-THSD7A antibodies AND Screening UPCR ≥3.5 g/g. Less than 50% reduction of proteinuria in the past 24 weeks prior to the start of screening despite on maximally tolerated angiotensin converting enzyme inhibitors (ACEis)/angiotensin II receptor blockers (ARBs) for more than 12 weeks No background immunosuppression therapies except for optional calcineurin inhibitors. LN A Biopsy-confirmed diagnosis of Class III, IV, or V LN ≤3 years prior to the start of screening AND Screening UPCR ≥1 g/g, with active urinary sediment OR additional criteria per protocol Positive anti-dsDNA at screening or within 12 weeks prior to the start of screening Positive anti-nuclear antibody On stable background immunosuppression ≥ 4 weeks prior to the start of screening On maximal dose or the maximally tolerated dose ACEis/ARBs for ≥12 weeks prior to study Day 1 Key Exclusion Criteria Summary: Prior diagnosis of, or fulfills diagnostic criteria for, another renal disease eGFR <30 mL/min/1.73m2 or rapidly progressive glomerulonephritis Recent serious or ongoing infection; risk or history of serious infection Receipt of B cell depleting therapies or anti-BAFF/APRIL therapies within 24 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: povetacicept 80mg<br> | Drug: povetacicept<br>* Administered by subcutaneous injection every 4 weeks<br>* Other names: ALPN-303;|
| Experimental: povetacicept 240mg<br> | Drug: povetacicept<br>* Administered by subcutaneous injection every 4 weeks<br>* Other names: ALPN-303;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Type, incidence, severity, and seriousness of AEs | Study Day 1 through 30 days after last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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