An Update on the Current State of Management and Clinical Trials for IgA Nephropathy
Abstract
:1. Introduction
2. Current Treatment Strategies
3. Systemic Corticosteroid Treatment
4. Clinical Trial Design in IgAN
5. The Gut Mucosal Immune system and IgAN
6. Targeting B Cells
7. Complement System Inhibitors
8. Non-immune Modulators
8.1. Endothelin Receptor Antagonists
8.2. Bardoxolone Methyl
8.3. Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i)
9. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Agent | Mechanism of Action | Clinical Trial Design | Clinical Outcomes (Reported/Being Investigated) |
---|---|---|---|
A. Targeting the Gut Mucosal Immune System | |||
TRF Budesonide | Corticosteroid formulation acts on distal ileum targeting B-cells in mucosal lymphoid tissue | Randomized, double-blind, placebo-controlled Phase II clinical trial (NEFIGAN)—completed * NCT01738035 |
|
Randomized, double-blind, placebo-controlled Phase III clinical trial (NefIgArd)—recruiting * NCT03643965 |
| ||
Fecal microbiota transplantation | Restoration of intestinal microecological balance | Open-Label Phase II clinical trial—recruiting * NCT03633864 |
|
B. Targeting B-cells | |||
Bortezomib | Semi-selective plasma cell proteasome inhibitor | Open-label Phase IV clinical trial—completed * NCT01103778 |
|
Fostamatinib | Oral spleen tyrosine kinase inhibitor | Randomized, double-blind, placebo-controlled Phase II clinical trial—completed * NCT02112838 |
|
Atacicept | Blocks downstream effects of BAFF and APRIL | Randomized, double-blind, placebo-controlled Phase II clinical trial—terminated (slow enrollment) * NCT02808429 |
|
Randomized, double-blind, placebo-controlled Phase II clinical trial (ORIGIN)—not yet recruiting * NCT04716231 |
| ||
Blisibimod | Selective BAFF antagonist | Randomized, double-blind, placebo-controlled Phase II/III clinical trial—completed * NCT02062684 |
|
VIS649 | Monoclonal antibody against APRIL | Randomized, double-blind, placebo-controlled Phase II clinical trial (enVISion)—recruiting * NCT04287985 |
|
BION-1301 | Monoclonal antibody against APRIL | Open-label, non-randomized Phase II Clinical trial—recruiting |
|
Hydroxychloroquine | Immunomodulator, inhibits mucosal and intrarenal Toll-like receptor signaling | Randomized, double-blind, placebo-controlled Phase II clinical trial—completed * NCT02942381 |
|
C. Complement System Inhibitors | |||
Ravulizumab | Humanized monoclonal antibody against C5 | Randomized, double blind, placebo-controlled Phase II clinical trial—recruiting * NCT04564339 |
|
Avacopan (CCX168) | C5a receptor blocker | Open-label Phase II clinical trial—completed * NCT02384317 |
|
Cemdisiran | Small-interfering RNA inhibits synthesis of C5 | Randomized, double-blind, placebo-controlled Phase II clinical trial—recruiting * NCT03841448 |
|
Pegcetacoplan (APL-2) | Peptide inhibitor of C3 | Open-Label Phase II clinical trial—active; not recruiting * NCT03453619 |
|
Iptacopan (LNP023) | Oral inhibitor of complement factor B | Randomized, double blind, placebo-controlled Phase II clinical trial—active, not recruiting * NCT03373461 |
|
Randomized, double blind, parallel-group, placebo-controlled Phase III clinical trial (APPLAUSE-IgAN) —recruiting * NCT04578834 |
| ||
IONIS-FB-LRx | Anti-sense inhibitor of complement factor B | Open-Label Phase II clinical trial—recruiting * NCT04014335 |
|
Narsoplimab (OMS721) | Monoclonal antibody against MASP-2 | Open-Label Phase II clinical trial—recruiting * NCT02682407 |
|
Randomized, double-blind, placebo-controlled Phase III clinical trial (ARTEMIS-IGAN)—recruiting * NCT03608033 |
| ||
D. Non-Immune Modulators | |||
Sparsentan | Selective antagonist of angiotensin II receptor and endothelin A receptor | Open-label Phase II clinical trial (SPARTAN)—recruiting * NCT04663204 |
|
Randomized, double-blind, parallel-group, active-control Phase III clinical trial (PROTECT)—recruiting * NCT03762850 |
| ||
Atrasentan | Selective antagonist of endothelin A receptor | Open-label Phase II clinical trial (AFFINITY)—recruiting * NCT04573920 |
|
Randomized, double-blind, placebo-controlled Phase III clinical trial (ALIGN)—recruiting * NCT04573478 |
| ||
Bardoxolone methyl | Semi-synthetic triterpenoid, activator of Nrf2 pathway, inhibitor of NF-ĸB pathway | Non-randomized, open-label, parallel-assignment Phase II clinical trial (PHOENIX)—completed * NCT03366337 |
|
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Cheung, C.K.; Rajasekaran, A.; Barratt, J.; Rizk, D.V. An Update on the Current State of Management and Clinical Trials for IgA Nephropathy. J. Clin. Med. 2021, 10, 2493. https://doi.org/10.3390/jcm10112493
Cheung CK, Rajasekaran A, Barratt J, Rizk DV. An Update on the Current State of Management and Clinical Trials for IgA Nephropathy. Journal of Clinical Medicine. 2021; 10(11):2493. https://doi.org/10.3390/jcm10112493
Chicago/Turabian StyleCheung, Chee Kay, Arun Rajasekaran, Jonathan Barratt, and Dana V. Rizk. 2021. "An Update on the Current State of Management and Clinical Trials for IgA Nephropathy" Journal of Clinical Medicine 10, no. 11: 2493. https://doi.org/10.3390/jcm10112493
APA StyleCheung, C. K., Rajasekaran, A., Barratt, J., & Rizk, D. V. (2021). An Update on the Current State of Management and Clinical Trials for IgA Nephropathy. Journal of Clinical Medicine, 10(11), 2493. https://doi.org/10.3390/jcm10112493