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RECRUITING

NCT05679336

Rituximab, Cyclophosphamide, and Corticosteroids in Primary Membranous Nephropathy

Sponsor: St. Petersburg State Pavlov Medical University

View on ClinicalTrials.gov

Summary

This exploratory study aims to assess the efficacy, safety of the experimental treatment based on a combination of rituximab (RTX), intravenous (IV) cyclophosphamide (CYC), and corticosteroids (S) administrated at lower cumulative doses (RCP) for the induction of early remission in subjects with anti-PLA2R antibody-positive primary membranous nephropathy (PMN) having nephrotic syndrome (NS).

Official title: Rituximab, Cyclophosphamide, and Corticosteroids at Low Cumulative Doses to Induce Remission in Primary Membranous Nephropathy

Key Details

Gender

All

Age Range

18 Years - 75 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2018-05-01

Completion Date

2024-08-31

Last Updated

2024-05-07

Healthy Volunteers

Conditions

Membranous Nephropathy - PLA2R Induced

Interventions

DRUG

Rituximab, Cyclophosphamide, and Corticosteroids

1. Rituximab (RTX) will be given as a single intravenous (IV) dose of 375 mg/m2. Extra RTX infusion at the same dose will be administered on weeks 12, 24, and 36 in the absence of remission and the occurrence of peripheral B-cell reconstitution. Peripheral B-cell reconstitution is defined as total CD19+ cell count \>5 cells/μL; 2. Concurrent with RTX initiation, a single IV infusion of methylprednisolone 500 mg will be administrated, followed by oral prednisolone 1 mg/kg daily but not exceeding 60 mg daily during week 1. The dosage will be rapidly decreased by 10 mg/weekly as follows: week 2, 50 mg daily; week 3, 40 mg daily; week 4, 30 mg daily; week 5, 20 mg daily; weeks 6-7, 10 mg daily; weeks 8-48, 5 mg daily; week 49, stop; 3. Four IV infusions of Cyclophosphamide will be administered at a dose of 7.5 mg/kg every other week (on weeks 1, 3, 5, and 7).

Inclusion Criteria: 1. Age 18-75 years. 2. Biopsy-proven primary membranous nephropathy (PMN) defined upon the exclusion of any significant concomitant disease (infectious, autoimmune, neoplastic) by careful clinical work-up at the time of kidney biopsy. 3. Signed informed consent 4. Increased serum level of anti-PLA2R antibodies (\>20 RU/ml). 5. Absence of contraindications to immusuppressive therapy. 6. Presence of nephrotic syndrome (NS) with one of the following conditions: 1. persistence for \>6 months despite treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker with or without immunosuppression and NS complications. 2. persistence for \<6 months at the presence of complications related to NS (thromboembolic or infectious event or estimated GFR by CKD-EPI equation (eGFR) decrease \>20%. 3. recurrence after remission with a prior immunosuppressive treatment. 4. treatment failure of an alternative immunosuppressive regimen. Exclusion Criteria: 1. Presence of a secondary cause of membranous nephropathy (e.g. hepatitis B, systemic lupus erythematosus, medications, malignancies). 2. Presence of Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy. 3. Acute or chronic infection, including: current use of suppressive therapy for chronic infection, hospitalization for treatment of infection in the past 60 days, or parenteral anti-microbial (including anti-bacterial, anti-viral, or anti- fungal agents) use in the past 60 days for infection. 4. Women of child-bearing potential who are pregnant, nursing, or unwilling to be sexually inactive or use FDA-approved contraception until study week. 5. A history of mental illness (including any history of suicidal behavior in the last 6 months, any suicidal ideation in the last 2 months, or who, in the investigator's judgment, pose a significant suicide risk). 6. A history of immunodeficiency, including other acquired or congenital immunodeficiency diseases, or organ transplantation. 7. Vaccination with a live vaccine within the past 30 days. 8. Evidence of current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence in the past 12 months. 9. Inability to comply with study and follow-up procedures. 10. Laboratory tests meeting any of the following: Hemoglobin \<80 g/L; Platelet \<80 x 109/ L; Neutrophil \<1.0×109/ L; Aspartate aminotransferase (AST) or amino acid aminotransferase (ALT) \>2.5× upper limit of normal. 11. Any patient judged by the investigator to be ineligible for enrollment in the trial. 12. eGFR ≤30 ml/min/1.73m2 in one measurement performed at baseline

Locations (1)

St. Petersburg State Pavlov Medical University

Saint Petersburg, Russia