Rituximab Combined With Cyclosporine Versus Rituximab Alone in the Treatment of iMN

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Terminated; Phase 3

Conditions: Idiopathic Membranous Nephropathy

Treatments: Drug: Rituximab; Drug: cyclosporine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04743739

iMN RTX plus CsA

Details and patient eligibility

About

The primary objective of this study is to determine whether or not cyclosporine (CsA) combined with RTX is more effective than RTX alone in the treatment of idiopathic membranous nephropathy (iMN).

Full description

To date, the first-line immunosuppressive therapy of iMN includes corticosteroids combined with cyclophosphamide or Rituximab (RTX) which has been used more and more widely due to superior safety profiles. But the long term remission rate of RTX monotherapy is only 60% and it takes effect relatively slowly.

2 pilot studies reported that the combination therapy of cyclosporine (CsA) and RTX had better efficacy for inducing remission for iMN, with the long term remission rate up to 85%. CsA and RTX may have synergistic effect in the treatment of iMN because they have different time of action and different effects on the immune system and podocytes.

Based on the previous rationale, the investigators designed this trial to determine whether combination of CsA and RTX is more effective than RTX alone in the treatment of iMN.

Enrollment: 12 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• idiopathic MN with or without diagnostic biopsy
• Female, must be post-menopausal, sterile or have effective method of contraception
• must be off steroid or mycophenolate mofetil for >1 month and alkylating agents for > 6 months
• Angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for ≥3 months prior to randomization with controlled blood pressure or if patients is intolerant to ACEI/ARB
• proteinuria ≥4g/24h using the average from two 24-hour urine samples collected within 2 weeks of each other, and decreased ≤50% from baseline.
• estimated glomerular filtration rate (eGFR) ≥40ml/min/1.73m2

Exclusion criteria

• presence of active infection or a secondary cause of MN
• diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy.
• pregnancy or breast feeding
• history of resistance to CsA or other calcineurin inhibitors(CNI), RTX or alkylating agents.
• Patients who previously achieved remission after treatment of CNI, RTX or alkylating agents but relapsed off CNI after 3 months, or relapsed off RTX or alkylating agents after 6 months, are eligible.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Rituximab monotherapy

Active Comparator group

Description:

Rituximab 1000mg I.V. on Days 1 and 181, and will be retreated or not on Days 15 and 195 according to the CD19+ B cells count.

Treatment:

Drug: Rituximab

Rituximab combined with cyclosporine

Experimental group

Description:

Rituximab 1000mg I.V. on Days 1 and 181, and will be retreated or not on Days 15 and 195 according to CD19+ B cells count. cyclosporine (CsA) will be started at a dose of 3mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Doses of CsA will be adjusted according to the blood levels of CsA. CsA will be tapered after 6 months and discontinued over a 3 month period.

Treatment:

Drug: cyclosporine

Drug: Rituximab