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Lupus NephritisPhase 1/2RUBY-3NCT05732402

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

A Phase 1/2 study testing Povetacicept in people with Lupus Nephritis and Immunoglobulin A Nephropathy, run by Alpine Immune Sciences, Inc. at 30 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Povetacicept
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
30 sitesin 4 countries
Study dates
15 Mar 2023to 2 Mar 2028
Phase
Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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,
  • 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
  • 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.

Who cannot join

  • 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:
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  • 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

Trial locations and contacts

30 sites in 4 countries.

30 sites in 4 countries

United States18 sites

  • Investigational Site (511)

    Albany, New York, 12209

  • Investigational Site (513)

    Arvada, Colorado, 80002

  • The Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21224

  • Investigational Site (518)

    Bethlehem, Pennsylvania, 18017

  • Investigational Site (503)

    Boston, Massachusetts, 02115

  • Investigational Site (508)

    Brooklyn, New York, 11203

  • Investigational Site (118)

    Colleyville, Texas, 76034

  • Investigational Site (516)

    Houston, Texas, 77054

  • Investigational Site (526)

    Irving, Texas, 75061

  • Investigational Site (502)

    Lawrenceville, Georgia, 30046

  • Investigational Site (509)

    Newark, New Jersey, 07103

  • Investigational Site (512)

    Orlando, Florida, 32806

  • Investigational Site (523)

    Phoenix, Arizona, 85016

  • Investigational Site (501)

    Phoenix, Arizona, 85302

  • Washington University School of Medicine in St. Louis

    St Louis, Missouri, 63110

  • Investigational Site (525)

    Tamarac, Florida, 33321

  • Investigational Site (524)

    Tucson, Arizona, 85712

  • Investigational Site (506)

    Valencia, California, 91335

Other trials in United States

South Korea8 sites

  • Investigational Site (505)

    Anyang-si, Gyeonggi-do, 14068

  • Investigational Site (507)

    Cheonan, Chungcheongnam-do, 31151

  • Investigational Site (504)

    Goyang-si, Gyeonggi-do, 10444

  • Investigational Site (510)

    Guri-si, Gyeonggi-do, 11923

  • Investigational Site (125)

    Seoul, Gyeonggi-do, 03080

  • Investigational Site (520)

    Seoul, Gyeonggi-do, 03181

  • Investigational Site (521)

    Seoul, Gyeonggi-do, 05278

  • Investigational Site (116)

    Suwon, Gyeonggi-do, 16499

Other trials in South Korea

Australia3 sites

  • Investigational Site (519)

    Concord, New South Wales, 2139

  • Investigational Site (102)

    Nedlands, Western Australia, 6009

  • Investigational Site (515)

    Saint Albans, Victoria, 3021

Other trials in Australia

Puerto Rico1 site

  • Investigational Site (191)

    Caguas, 00725

Other trials in Puerto Rico

About this study

Official 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)

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.

Being tested
Povetacicept
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
Medical subject headings
Lupus Nephritis, Glomerulonephritis, IGA, Glomerulonephritis, Membranous, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Microscopic Polyangiitis, Granulomatosis with Polyangiitis, Churg-Strauss Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PovetaciceptDrug

    Also called ALPN-303

    Administered by subcutaneous injection every 4 weeks

Study groups in NCT05732402
Study groupRoleWhat they receive
PovetaciceptExperimentalPart 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.
Receives: Drug: Povetacicept

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

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

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

Secondary outcomes (21)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  9. 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

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

  10. 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

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

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

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

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

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

  13. Part A: Immunological Remission (pMN only)

    Measured: Study Day 1 Through Week 24 After Dose of Study Drug

  14. Part B: Immunological Remission (pMN only)

    Measured: Study Day 1 Through Week 12 After Dose of Study Drug

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

    Measured: Baseline and at Week 24

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

    Measured: Baseline and at Week 24

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

    Measured: Baseline and at Week 24

  18. Part A: Renal Response

    Measured: At Week 24

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

    Measured: At Week 24

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

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

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2023
  2. Study start15 Mar 2023
  3. Primary completion2 Mar 2028 (estimated)
  4. Study completion2 Mar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05732402
Sponsor's protocol ID
AIS-D03
Acronym
RUBY-3
Status last verified
Oct 2026
First submitted
8 Feb 2023
Last updated
20 Oct 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

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