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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 March 2025
• Main ID: NCT05732402
• Date of registration: 08/02/2023
• Prospective Registration: Yes
• Primary sponsor: Alpine Immune Sciences, Inc.
• Public title: An Open-label Study of Povetacicept in Autoantibody-Associated Glomerular Diseases RUBY-3
• Scientific title: 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)
• Date of first enrolment: March 15, 2023
• Target sample size: 296
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT05732402
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, Austria, Korea, Republic of, Norway, Puerto Rico, Spain, United Kingdom, United States

Contacts

• Name: Medical Information

Key inclusion & exclusion criteria

Key Inclusion Criteria Summary:

1. Biopsy-confirmed autoantibody-associated glomerular disease: immunoglobulin A
nephropathy (IgAN), primary membranous nephropathy (pMN), or lupus nephritis (LN) 2.

Indication-specific criteria:

a. 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.

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,

- Positive anti-dsDNA at screening

- On stable background immunosuppression = 8 weeks prior to Day 1

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.

3. On maximal dose or the maximally tolerated dose ACEis/ARBs for =12 weeks prior
to study Day 1

Key Exclusion Criteria Summary:

1. Prior diagnosis of, or fulfills diagnostic criteria for, another renal disease

2. eGFR <30 (milliliter per minute per square meter (mL/min/1.73m^2) or rapidly
progressive glomerulonephritis

3. Recent serious or ongoing infection; risk or history of serious infection

4. Receipt of B cell depleting therapies or anti-BAFFand/or APRIL therapies within
protocol specified timeframes


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Immunoglobulin A Nephropathy

Lupus Nephritis

Membranous Nephropathy

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Intervention(s)

Drug: Povetacicept

Primary Outcome(s)

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]

Secondary Outcome(s)

Change from Baseline in Peripheral Blood Lymphocytes and Subsets [Time Frame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug]

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]

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]

Change from Baseline at Week 24 in Estimated Glomerular Filtration Rate (eGFR) [Time Frame: Baseline and at Week 24]

Immunological Remission [Time Frame: At 12, 24, 36, 48, and 52 Weeks]

Remission of Vasculitis (Birmingham Vasculitis Activity Score (BVAS = 0)) (for AAV cohorts only) [Time Frame: At Week 24]

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]

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]

Renal Response [Time Frame: At Week 24]

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]

Change from Baseline Over Time In Circulating Levels Of anti-dsDNA in LN; galactose deficient IgA1 (Gd-IgA1); anti-PLA2R1 or anti THSD7A in pMN and anti-PR3 or anti-MPO in Anti-neutrophil Cytoplasmic Antibody Associated Vasculitis (AAV) [Time Frame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug]

Incidence and Titer of Anti-drug Antibodies (ADA) Against Povetacicept [Time Frame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug]

Secondary ID(s)

AIS-D03

Source(s) of Monetary Support

Please refer to primary and secondary sponsors