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MOR202 for Refractory MN

NCT04893096 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 10

Last updated 2025-03-25

No results posted yet for this study

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.

Conditions

Interventions

DRUG

MOR202

Each patient will be treated for 24 weeks and received a total of 9 doses. During the first treatment cycle, MOR202 will be administered weekly. For the following 5 months, patients will receive one dose every 4 weeks.

Sponsors & Collaborators

  • MorphoSys AG

    collaborator INDUSTRY

  • Mario Negri Institute for Pharmacological Research

    lead OTHER

Principal Investigators

  • Giuseppe Remuzzi, MD · Istituto Di Ricerche Farmacologiche Mario Negri

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2021-10-22
Primary Completion
2025-02-21
Completion
2025-02-21

Countries

  • Italy

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04893096 on ClinicalTrials.gov