Rituximab, Cyclophosphamide, and Corticosteroids in Primary Membranous Nephropathy

NCT05679336 | Recruiting

• 1 other identifier: VD-266/MN
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Membranous Nephropathy - PLA2R Induced

Keywords

Rituximab; Corticosteroids; Cyclophosphamide; Clinical and immunological remissions; Membranous nephropathy; Nephrotic syndrome

Outcome Measures

Primary Outcomes (2)

• Partial clinical remission (PR) and complete clinical remission (CR)

  Including the proportion of participants with complete and partial responses by month 12 since the treatment initiation; CR defined as proteinuria of \<0.3 g/1.73 m2/24h and serum albumin \>30 g/l; PR defined as a ≥50% reduction in proteinuria from baseline accompanied by a regress of nephrotic syndrome (NS)

  Up to 1 year

• Time to clinical remission

  Cumulative rate of overall (complete and partial) clinical remission and complete clinical remission by month 12

  Up to 1 year

Secondary Outcomes (7)

• The time to immunologic remission

  Through study completion, an average of 2 years

• The change in circulating CD19+ cells

  Up to 1 year

• The change in proteinuria

  Up to 1 year

• The change in estimated GFR (eGFR)

  Through study completion, an average of 2 years

• The change in serum albumin

  Up to 1 year

Study Arms (1)

Rituximab, Cyclophosphamide, and Corticosteroids group

EXPERIMENTAL

The experimental treatment group: 40 participants will receive combined immunosuppressive therapy with Rituximab, Cyclophosphamide, and Corticosteroids.

Drug: Rituximab, Cyclophosphamide, and Corticosteroids

Interventions

Rituximab, Cyclophosphamide, and Corticosteroids DRUG

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).

Rituximab, Cyclophosphamide, and Corticosteroids group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years.
• Signed informed consent
• Increased serum level of anti-PLA2R antibodies (\>20 RU/ml).
• Absence of contraindications to immusuppressive therapy.
• Presence of nephrotic syndrome (NS) with one of the following conditions:
• persistence for \>6 months despite treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker with or without immunosuppression and NS complications.
• 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%.
• recurrence after remission with a prior immunosuppressive treatment.
• treatment failure of an alternative immunosuppressive regimen.

You may not qualify if:

• Presence of a secondary cause of membranous nephropathy (e.g. hepatitis B, systemic lupus erythematosus, medications, malignancies).
• Presence of Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy.
• 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.
• Women of child-bearing potential who are pregnant, nursing, or unwilling to be sexually inactive or use FDA-approved contraception until study week.
• 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).
• A history of immunodeficiency, including other acquired or congenital immunodeficiency diseases, or organ transplantation.
• Vaccination with a live vaccine within the past 30 days.
• Evidence of current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence in the past 12 months.
• Inability to comply with study and follow-up procedures.
• 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.
• Any patient judged by the investigator to be ineligible for enrollment in the trial.
• eGFR ≤30 ml/min/1.73m2 in one measurement performed at baseline

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

St. Petersburg State Pavlov Medical University

Saint Petersburg, 197022, Russia

RECRUITING

MeSH Terms

Conditions

Glomerulonephritis, Membranous; Nephrotic Syndrome

Interventions

Rituximab; Cyclophosphamide; Adrenal Cortex Hormones

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; Nephrosis

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Vladimir Dobronravov, Professor

  St. Petersburg State Pavlov Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vladimir Dobronravov, Professor

CONTACT

+7(812)338-69-01; dobronravov@nephrolog.ru

Zinaida Kochoyan

CONTACT

zinshak@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-director for science RM Gorbacheva Institute

Study Record Dates

• First Submitted: November 28, 2022
• First Posted: January 11, 2023
• Study Start: May 1, 2018
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)