Atacicept for IgA Nephropathy (ORIGIN EXTEND Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Vera Therapeutics, Inc.
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to collect long-term safety and tolerability data for atacicept in patients with IgAN that completed Vera trial investigating atacicept in IgAN population.
What safety data is available for Atacicept?Atacicept has been evaluated for safety in several studies. In healthy volunteers, it was assessed for safety, pharmacokinetics, and pharmacodynamics. A study in patients with lupus nephritis was prematurely terminated, but aimed to evaluate its safety in combination with other treatments. In a randomized trial, its safety and tolerability were compared in healthy Caucasian and Japanese subjects. Additionally, in patients with systemic lupus erythematosus, its safety was studied in both subcutaneous and intravenous forms, showing consistent and predictable pharmacokinetic profiles across doses and regimens.12345
Is Atacicept a promising drug for IgA Nephropathy?Yes, Atacicept is a promising drug for IgA Nephropathy because it targets B-cells, which are involved in the disease, and helps reduce harmful proteins in the body that can lead to kidney failure.13567
What data supports the idea that Atacicept for IgA Nephropathy is an effective treatment?The available research shows that Atacicept is a drug that targets specific proteins involved in immune system activity, which are important in the development of IgA Nephropathy. Although the studies provided do not directly show Atacicept's effectiveness for IgA Nephropathy, they indicate its potential by demonstrating its ability to reduce immune system activity in related conditions. For example, Atacicept has been shown to reduce levels of certain immune proteins in patients with autoimmune diseases, suggesting it could help manage IgA Nephropathy by targeting similar immune pathways. Additionally, another treatment, telitacicept, which works similarly to Atacicept, has shown promise in reducing symptoms like blood and protein in urine, which are key issues in IgA Nephropathy.12357
Do I need to stop my current medications to join the trial?The trial prohibits the use of systemic corticosteroids, immunosuppressive medications, and certain biologic therapies within specific timeframes before screening. If you are taking these, you may need to stop them to participate. The protocol does not specify other medications, so consult with the trial team for guidance.
Eligibility Criteria
This trial is for patients with IgA Nephropathy, a kidney disease, who have completed the Vera trial. It's designed to gather more information on the long-term safety and effects of Atacicept in this specific group.Inclusion Criteria
My blood pressure is 150/90 mmHg or lower.
Exclusion Criteria
I am unable or unwilling to follow the study's procedures.
My kidney function has rapidly declined by half in the last 3 months.
I have been treated for latent TB for at least 4 weeks without re-exposure.
I have had or am expected to have an organ transplant, except for corneal transplants.
I have not had major surgery in the last 6 weeks and do not plan any during the study.
I have had my spleen removed.
I am on dialysis or will start it within 3 months.
Treatment Details
The study focuses on evaluating the continued use of Atacicept at a dose of 150 mg. The goal is to understand its long-term impact on patients with IgA Nephropathy who previously participated in related research.
1Treatment groups
Experimental Treatment
Group I: Atacicept 150mg once weekly subcutaneous (SC) injectionExperimental Treatment1 Intervention
Other Names:
VT-001
Find a clinic near you
Research locations nearbySelect from list below to view details:
Vera TherapeuticsBrisbane, CA
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Who is running the clinical trial?
Vera Therapeutics, Inc.Lead Sponsor
References
Safety, pharmacokinetics and pharmacodynamics of atacicept in healthy volunteers. [2022]Atacicept, a recombinant fusion protein, blocks the activity of BLyS (a B-lymphocyte stimulator) and APRIL (a proliferation-inducing ligand) and may be a potential treatment for B-cell-mediated diseases. This study assesses the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of atacicept.
Pharmacokinetics and immunoglobulin response of subcutaneous and intravenous atacicept in patients with systemic lupus erythematosus. [2018]Atacicept, a recombinant fusion protein of the TACI receptor and human IgG, is an inhibitor of B-Lymphocyte Stimulator (BLyS) and APRIL, potent stimulators of B cell maturation, proliferation, and survival. Pharmacokinetics (PKs) and biological activity of intravenous (iv) and subcutaneous (sc) atacicept are described here for patients with systemic lupus erythematosus in two randomized, double-blind, placebo-controlled, Phase Ib studies. Study 1: Six cohorts of eight patients received sc atacicept (single dose: 0.3, 1, 3, or 9 mg/kg; four weekly doses: 1 or 3 mg/kg), or placebo (3:1 ratio). Study 2: Four cohorts of six patients received iv atacicept (single dose: 3, 9, or 18 mg/kg; multiple dose: 2 x 9 mg/kg), or matching placebo (5:1 ratio). PK profiles were determined through serum atacicept and atacicept-BLyS complex, and biological activity through IgA, IgG, and IgM levels. PK profiles of atacicept were influenced by saturable binding between atacicept and its ligands, and were consistent and predictable across doses and regimens. Atacicept's biological activity was compatible with its presumed mechanism of action. Bioavailability was approximately 30-40% following sc or iv administration and similar doses yielded similar biological activity irrespective of administration route. This observation may have a mechanistic foundation and may inform dosing regimen design for future studies.
Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. [2023]Atacicept is a soluble, fully human, recombinant fusion protein that inhibits B cell-stimulating factors APRIL (a proliferation-inducing ligand) and BLyS (B-lymphocyte stimulator). The APRIL- LN study aimed to evaluate the efficacy and safety of atacicept in patients with active lupus nephritis (LN), receiving newly initiated corticosteroids (CS) and mycophenolate mofetil (MMF).
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Atacicept in a Randomized Trial in Healthy Caucasian and Japanese Subjects. [2022]Atacicept is an inhibitor of the B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), and is being studied in relation to immunological disease. Currently, limited data on atacicept are available in non-Caucasian subjects. Pharmacokinetic data from earlier studies of atacicept were derived using an enzyme-linked immunosorbent assay (ELISA), which was subsequently found to have inadequacies. Hence, a new bioanalytical ELISA for total atacicept was developed and validated. We conducted this randomized, double-blind, placebo-controlled phase I study to compare the safety, tolerability, pharmacokinetics, and pharmacodynamics of atacicept in healthy Japanese and Caucasian subjects while generating pharmacokinetic data using the new ELISA.
Randomized Phase II JANUS Study of Atacicept in Patients With IgA Nephropathy and Persistent Proteinuria. [2022]Patients with IgA nephropathy (IgAN) and persistent proteinuria are at risk of progression to kidney failure. Atacicept is a novel B-cell-targeted immunomodulator, shown to reduce immunoglobulin levels in patients with autoimmune diseases.
Telitacicept for autoimmune nephropathy. [2023]B cells and the humoral immunity are important players in the pathogenesis of autoimmune diseases. BAFF (also known as BLYS) and a proliferation-inducing ligand APRIL are required for the maintenance of the B-cell pool and humoral immunity. BAFF and APRIL can promote B-cell differentiation, maturation, and plasma cell antibody secretion. BAFF/APRIL overexpression has been identified in several autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, IgA nephropathy, etc. Telitacicept, a novel fully human TACI-Fc fusion protein that binds both BAFF and APRIL, was approved in China in March 2021 for the treatment of systemic lupus erythematosus at a recommended dose of 160 mg/w subcutaneously and is in clinical trials for the treatment of multiple indications in other autoimmune diseases. In this review, we explored telitacicept's mechanism of action and clinical data. In addition, the immune features of autoimmune nephropathy were discussed, emphasizing lupus nephritis, IgA nephropathy, and membranous nephropathy.
Role of telitacicept in the treatment of IgA nephropathy. [2023]IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and up to 40% of patients with IgAN develop end-stage renal disease (ESRD). At present, an increasing amount of evidence indicates that the pathogenesis of IgAN is related to autoimmunity. In recent years, several studies have shown that B cell activating factors (BAFF), also known as B lymphocyte stimulators (BLyS), and proliferation-inducing ligand APRIL are extremely important for the activation of autoimmune signalling pathways, which have become key targets for the treatment of IgAN. As a dual-target biological agent, telitacicept can inhibit both BLyS and APRIL cytokines, improve the function of renal immune complexes, and reduce haematuria and proteinuria, which play important roles in IgAN pathogenesis and long-term prognosis. This article reviews the role of telitacicept in IgA nephropathy and discusses its potential for use in the treatment of IgAN and other autoimmune diseases where pathogenesis is driven by B cells.