Combination treatment for primary membranous nephropathy

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

This study is testing a new combination treatment for people with a specific type of kidney disease to see if it can help them feel better faster and reduce the chances of serious complications.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: St. Petersburg State Pavlov Medical University (Academic / other)
• Drugs / interventions: rituximab, cyclophosphamide
• Locations: 1 site (Saint Petersburg)
• Trial ID: NCT05679336 on ClinicalTrials.gov

What this trial studies

This exploratory study evaluates the efficacy and safety of a new treatment regimen combining rituximab, intravenous cyclophosphamide, and corticosteroids for patients with anti-PLA2R antibody-positive primary membranous nephropathy who are experiencing nephrotic syndrome. The goal is to induce early remission using lower cumulative doses of these medications. The study aims to address the high treatment failure rates seen with standard therapies and improve patient outcomes by rapidly inducing remission and reducing the risk of severe complications associated with the disease.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-75 with biopsy-proven primary membranous nephropathy and elevated anti-PLA2R antibody levels experiencing nephrotic syndrome.

Not a fit: Patients with significant concomitant diseases or contraindications to immunosuppressive therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could lead to improved remission rates and reduced complications for patients with primary membranous nephropathy.

How similar studies have performed: While there have been studies on immunosuppressive therapies for membranous nephropathy, this specific combination approach is novel and has not been extensively tested.

Eligibility 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

Where this trial is running

Saint Petersburg

• St. Petersburg State Pavlov Medical University — Saint Petersburg, Russia (Recruiting)

Study contacts

• Principal investigator: Vladimir Dobronravov, Professor — St. Petersburg State Pavlov Medical University
• Study coordinator: Vladimir Dobronravov, Professor

Conditions Membranous Nephropathy - PLA2R Induced; Rituximab; Corticosteroids; Cyclophosphamide; Clinical and immunological remissions; Membranous nephropathy; Nephrotic syndrome