Rituximab, Cyclophosphamide, and Corticosteroids in Primary Membranous Nephropathy

• Status: Recruiting
• Trial end date: 2024-08-31
• Target enrollment: 0
• Participant gender: All

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).

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Petersburg State Pavlov Medical University
• Treatments: Cyclophosphamide; Rituximab

Criteria

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