MOR202 for Refractory MN

NCT04893096 | Completed Phase 2 DMC

• 2 other identifiers: MONET2021-000835-30
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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

Membranous Nephropathy

Keywords

membranous nephropathy; Anti-CD38; MOR 202

Outcome Measures

Primary Outcomes (2)

• Change in 24-hour urinary protein excretion

  Changes from screening and baseline, 1, 5,6,9,12,18 and 24 months after the first MOR202 administration.

• Complete remission or partial remission of nephrotic syndrome.

  Complete remission is intended as : 24-hour urinary protein excretion \<0.3 g or urinary protein to creatinine ratio \< 300 mg/g, with serum albumin \> 3.5 g/dL. Partial remission is intended as: 24-hour urinary protein excretion \<3.5 g or urinary protein to creatinine ratio \< 3500 mg/g, with at least 50% reduction compared to baseline.

  Changes from screening and baseline, 1, 5,6,9,12,18 and 24 months after the first MOR202 administration.

Study Arms (1)

MOR202 (felzartamab) infusion

EXPERIMENTAL

Participants will receive active treatment for a total of nine doses during 24 weeks.

Drug: MOR202

Interventions

MOR202 DRUG

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.

Also known as: FELZARTAMAB

MOR202 (felzartamab) infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Biopsy-proven membranous nephropathy with or without detectable circulating anti-PLA2R or anti-THSD7A antibodies.
• Background treatment with RAS blocking agents (ACE inhibitor and/or ARBs), at maximum tolerated doses and adequately controlled blood pressure (BP \<140/90 mmHg in at least three consecutive readings at screening).
• One condition between:
• Anti-CD20 Resistance: residual proteinuria ≥3.5 g/day (mean of three consecutive 24-hour urine collections), with less than 50% reduction compared to pre-treatment values at least 12 months after anti-CD20 antibody therapy.
• Anti-CD20 Dependence: frequently relapsing NS (nephrotic-range proteinuria for \>50% of time in the last five years or since disease onset, whichever is shorter) despite repeated treatments with anti-CD20 antibodies.
• Estimated GFR \>30 ml/min/1.73m2 (CKD-EPI equation) and less than 50% of sclerotic glomeruli in patients receiving renal biopsy.
• A minimum 12-month wash-out from last anti-CD20 therapy with rituximab and/or other monoclonal antibodies.
• No significant (i.e. more than 2 weeks) immunosuppressive therapy over the last 6 months.
• Written informed consent.

You may not qualify if:

• Clinically relevant neutropenia (neutrophils \< 1.5 x 109/L), anemia (Hb levels \<9.0 g/dL), thrombocytopenia (platelet count \< 150.000/mm3), increased liver transaminase or bilirubin levels (total bilirubin, aspartate aminotransferase or alanine aminotransferase \>1.5 x ULN, alkaline phosphatase \>3.0 x ULN).
• Significant uncontrolled cardiovascular disease (including arterial or venous thrombotic or embolic events over the last three months) or cardiac insufficiency (New York Heart Association \[NYHA\] class IV) as judged by the investigator.
• Clinically relevant findings on a 12-lead electrocardiogram (ECG) as determined by the investigator at screening.
• History of significant cerebrovascular disease (stroke or transitory ischemic attack over the last three months) or sensory or motor neuropathy of toxicity ≥ grade 3.
• Any clinical condition that in the investigator judgment could affect the possibility to complete the study or could have a major confounding effect on study findings and data interpretation.
• Known intolerance to the study drug or its excipients
• Any viral, bacterial or fungal infection without complete symptoms resolution from at least two weeks.
• Serologic or virologic markers positive for HIV, hepatitis C (patients with positive antihepatitis C virus \[anti-HCV\] antibody but negative HCV RNA polymerase chain reaction \[PCR\] can enroll) or active or latent hepatitis B (patients with positive hepatitis B surface antigen \[HBsAg\] are excluded). Patients with isolated positive hepatitis B core antibody \[anti-HBc\], hepatitis B virus (HBV) DNA test by PCR must be non-detectable to enroll.
• History of malignancy within the prior 5 years.
• Participation in other clinical trials within 4 weeks of signing the consent form.
• Expected need of anti SARS Cov 2 vaccination during the study period
• Pregnancy or breast-feeding.
• Childbearing potential in males and females non using an highly effective method of contraception according to 2020 CTFG Recommendations related to contraception and pregnancy testing in clinical trials (https://www.hma.eu/fileadmin/dateien/Human\_Medicines/01-About\_HMA/Working\_Groups/CTFG/2020\_09\_HMA\_CTFG\_Contraception\_guidance\_Version\_1.1\_updated.pdf).
• Legal incapacity or limited legal capacity.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• MorphoSys AG: collaborator

Study Sites (2)

ASST HPG23 - Unità di Nefrologia

Bergamo, BG, 24100, Italy

Location

Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"

Ranica, BG, 24020, Italy

Location

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Interventions

felzartamab

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Giuseppe Remuzzi, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: May 19, 2021
• Study Start: October 22, 2021
• Primary Completion: February 21, 2025
• Study Completion: February 21, 2025
• Last Updated: March 25, 2025

Record last verified: 2025-03

Locations

IT (2)