Efficacy of Rituximab Combined With Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy

Efficacy and Safety of Low Dose Rituximab Combined With Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy

Idiopathic membranous nephropathy (IMN) is one of the common types of primary glomerular diseases and the most common cause of nephrotic syndrome in adults.

Poticelli regimen is the classic treatment, but cyclophosphamide has many toxic side effects. The period of glucocorticoid therapy is relatively long, and the adverse reactions caused by glucocorticoid therapy cannot be ignored. For patients who are unwilling to receive glucocorticoids and cyclophosphanide or who have treatment contraindications, cyclosporine can be used, mainly cyclosporine and tacrolimus, with the rapid overall effect but a high short-term relapse rate. In recent years, rituximab therapy has become a first-line treatment, with a high remission rate, and few side effects, but expensive. In terms of efficacy alone, the above regimen did not exceed Poticelli regimen. However, the toxic side effects of rituximab, cyclosporine may be lower than that of Poticelli regimen. Based on the preliminary experiment, this study explored a new treatment plan: low-dose rituximab combined with cyclosporine in the treatment of IMN, the efficacy is not inferior to Poticelli regimen, but the side effects are significantly reduced. The result will provide a good choice for IMN patients.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Membranous Nephropathy
• Intervention / Treatment: Drug: Rituximab; Drug: Modified Ponticelli regimen

• Study Type: Interventional
• Enrollment (Anticipated): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100050
    • Recruiting
    • Beijing Friendship Hospital, Capital Medical University
    • Contact: Zongli Diao, M.D.; Phone Number: +861063138679; Email: diaozl@ccmu.edu.dn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age 18-70 years; serum albumin level <30 g/L;
2. estimated glomerular filtration rate (eGFR according to the CKD-EPI formula) ≥60 mL/min per 1.73 m2;
3. patients with a moderate risk of IMN and decline <50% in proteinuria despite blockade of the renin-angiotensin system 3 months before randomization;
4. patients at high risk or very high risk of IMN.

Exclusion Criteria:

1. secondary causes of MN;
2. being pregnant or breastfeeding;
3. uncontrollable active infectious disease;
4. immunosuppressive treatment in the preceding 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rituximab; Patients received rituximab 100 and 500 mg of intravenous medication on days 1 and 2, respectively. If proteinuria was reduced from baseline by no more than 25% at 3 months, cyclosporine was administered. In addition, CD19+ B-cell count was monitored every 3 months, and another rituximab 100 and 500 mg will be administered if CD19+ B-cell count >5 cells/mL.	Drug: Rituximab; Rituximab combined with or without cyclosporine
Active Comparator: Modified Ponticelli regimen; Patients received corticosteroids at months 1, 3, and 5 (methylprednisolone 0.5 g at days 1, 2, and 3, then prednisone 0.5 mg/kg/d from day-4 to day-30). At months 2, 4, and 6, patients received cyclophosphamide adjusted for age and renal function (1.0-2.0 mg/kg/day for 30 days, maximum dose 100 mg/d).	Drug: Modified Ponticelli regimen; Corticosteroid and cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
remission of nehprotic syndrome	The primary clinical outcome was a composite outcome with complete remission or partial remission of nehprotic syndrome at 12 months. Complete remission was defined as a reduction of proteinuria to ≤ 0.3 g/24 h plus stable kidney function (eGFR ≥45 mL/min per 1.73 m2). Partial remission was defined as a reduction of proteinuria of ≥ 50% from baseline, and <3.5 g/24 h plus stable renal function (eGFR ≥45 mL/min per 1.73 m2).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission of nehprotic syndrome	Complete remission was defined as a reduction of proteinuria to ≤ 0.3 g/24 h plus stable kidney function (eGFR ≥45 mL/min per 1.73 m2).	12 months
adverse events	The prevalence of adverse events including infections, hyperglycemia etc will be recored.	12 months

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2022
• Primary Completion (Anticipated): December 4, 2023
• Study Completion (Anticipated): December 4, 2023

Study Registration Dates

• First Submitted: December 18, 2022
• First Submitted That Met QC Criteria: March 23, 2023
• First Posted (Actual): March 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, Membranous; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 2022-P2-250-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No