Clinical trial NCT05732402: An Open-label Study of Povetacicept in Autoantibody-Associated Glomerular Diseases
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lupus Nephritis
Immunoglobulin A Nephropathy
Membranous Nephropathy
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
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)
Lead sponsor: Alpine Immune Sciences, Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-17
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical study is to evaluate multiple dose levels of povetacicept in adults with immunoglobulin A (IgA) nephropathy, membranous nephropathy, lupus-related kidney disease (lupus nephritis). or anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis 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 .


Eligibility 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

Primary outcomes:
measure: Safety as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug
Secondary outcomes:
measure: Incidence and Titer of Anti-drug Antibodies (ADA) Against Povetacicept
timeFrame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug
measure: Time Required for Povetacicept To Reach Half its Concentration (t1/2)
timeFrame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug
measure: Change from Baseline in Serum Ig Isotypes (IgM, total IgA, IgA1, IgA2, total IgG, IgG1, IgG2, IgG3, IgG4, IgE).
timeFrame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug
measure: Change from Baseline in Peripheral Blood Lymphocytes and Subsets
timeFrame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug
measure: 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)
timeFrame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug
measure: Change From Baseline Over Time In Complement Components (C3, C4, CH50)
timeFrame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug
measure: Immunological Remission
timeFrame: At 12, 24, 36, 48, and 52 Weeks
measure: Change from Baseline at Week 24 in UPCR(Urine protein/creatinine ratio) (based on assessment of 24-hour urine)
timeFrame: Baseline and at Week 24
measure: Change from Baseline at Week 24 in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline and at Week 24
measure: Renal Response
timeFrame: At Week 24
measure: Remission of Vasculitis (Birmingham Vasculitis Activity Score (BVAS = 0)) (for AAV cohorts only)
timeFrame: At Week 24
measure: Changes in Biomarkers Including Cytokines and Autoantibodies After Treatment with Povetacicept
timeFrame: Study Day 1 Through 24 Weeks After Last Dose Of Study Drug
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Investigational Site (523)
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site (501)
state: Arizona
city: Tucson
country: United States
facility: Investigational Site (524)
state: Arizona
city: Valencia
country: United States
facility: Investigational Site (506)
state: California
city: Arvada
country: United States
facility: Investigational Site (513)
state: Colorado
city: Orlando
country: United States
facility: Investigational Site (512)
state: Florida
city: Tamarac
country: United States
facility: Investigational Site (525)
state: Florida
city: Lawrenceville
country: United States
facility: Investigational Site (502)
state: Georgia
city: Baltimore
country: United States
facility: The Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Investigational Site (503)
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Newark
country: United States
facility: Investigational Site (509)
state: New Jersey
city: Albany
country: United States
facility: Investigational Site (511)
state: New York
city: Brooklyn
country: United States
facility: Investigational Site (508)
state: New York
city: Bethlehem
country: United States
facility: Investigational Site (518)
state: Pennsylvania
city: Colleyville
country: United States
facility: Investigational Site (118)
state: Texas
city: Houston
country: United States
facility: Investigational Site (516)
state: Texas
city: Irving
country: United States
facility: Investigational Site (526)
state: Texas
city: Concord
country: Australia
facility: Investigational Site (519)
state: New South Wales
city: Saint Albans
country: Australia
facility: Investigational Site (515)
state: Victoria
city: Nedlands
country: Australia
facility: Investigational Site (102)
state: Western Australia
city: Cheonan
country: Korea, Republic of
facility: Investigational Site (507)
state: Chungcheongnam-do
city: Anyang-si
country: Korea, Republic of
facility: Investigational Site (505)
state: Gyeonggi-do
city: Goyang-si
country: Korea, Republic of
facility: Investigational Site (504)
state: Gyeonggi-do
city: Guri-si
country: Korea, Republic of
facility: Investigational Site (510)
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Investigational Site (125)
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Investigational Site (520)
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Investigational Site (521)
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: Investigational Site (116)
state: Gyeonggi-do
city: Caguas
country: Puerto Rico
facility: Investigational Site (191)
Study officials:
References: