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Clinical Trial Summary

Membranous nephropathy (MN) - the leading cause of nephrotic syndrome (NS) in adults - is an immune-mediated disease that results from the deposition of immunoglobulins and complement components onto the sub-epithelial layer of the glomerular capillary wall. The availability for clinical use of rituximab, a monoclonal antibody against the B-cell surface antigen CD20, offered the opportunity to test the effects of specific CD20-targeted intervention aimed to prevent B-cell dependent mechanisms resulting in the production of nephritogenic autoantibodies. Rituximab-induced B-cell depletion reduced proteinuria in eight patients with MN while avoiding the adverse effects of steroids and other immunosuppressants. Subsequent studies confirmed that rituximab is remarkably safer than non-specific immunosuppressive agents, including cyclosporine, and achieves remission in approximately two-thirds of patients with MN-associated nephrotic syndrome. After rituximab-induced remission, however, NS may relapse in approximately one third of patients. Thus, novel therapeutic options are needed for a substantial proportion of patients with MN who may fail rituximab therapy. Conceivably, in patients with MN refractory to CD20-targeted therapy, the production of nephritogenic autoantibodies is sustained by mechanisms that do not depend on autoreactive CD20+ B cells. Recently, it was shown that CD19-negative bone marrow plasma cells, which express CD38, are enriched in chronically inflamed tissue and secrete autoantibodies. Treatment of patients with MN with CD38-targeting antibodies may represent a new therapeutic approach. MOR202 is a fully human recombinant monoclonal antibody against CD38 that has demonstrated in-vitro and in-vivo efficacy in experimental models of multiple myeloma. Antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis are the principal mechanisms of action for MOR202-induced lysis of myeloma cells. The working hypothesis is that CD38-targeted therapy with MOR202 may abrogate autoantibody-dependent mechanisms in patients with plasma-cell mediated forms of MN who failed previous treatment with rituximab and second-generation anti-CD20 monoclonal antibodies such as ofatumumab. With this background, MOR202 therapy may have an indication for patients with MN and NS resistant to CD20 targeted therapy.


Clinical Trial Description

n/a


Study Design


Related Conditions & MeSH terms


NCT number NCT04893096
Study type Interventional
Source Mario Negri Institute for Pharmacological Research
Contact
Status Active, not recruiting
Phase Phase 2
Start date October 22, 2021
Completion date February 2025

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