MOR202 for Refractory MN (MONET)

This is an interventional treatment trial for Membranous Nephropathy focused on measuring membranous nephropathy, Anti-CD38, MOR 202 Read More

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.