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

Phase 3TerminatedNCT04743739

Peking Union Medical College Hospital12 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Idiopathic Membranous Nephropathy

Interventions

RituximabDRUG

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

cyclosporineDRUG

cyclosporine (CsA) will be started at a dose of 3mg/kg/d and adjusted according to the blood levels of the CsA. CsA will be tapered after 6 months and discontinued over a three month period.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (7)

Fuwai Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Beijing Tongren Hospital， Capital Medical University

Beijing, Beijing Municipality, China

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Beijing Luhe Hospital, Capital Medical University

Outcomes

Primary Outcomes

complete remission (CR) or partial remission (PR) at 24 month

complete or partial remission at 24 month. complete remission is defined as urine protein≤0.5g/24h and serum albumin≥3.5g/dl. Partial remission is defined as reduction in baseline urine protein ≥50% plus urine protein≤3.5g/24h but \>0.5g/24h

Time frame: 24 months after randomization

Secondary Outcomes

complete remission (CR) or partial remission (PR) on 6 month, 12 month, 18 month

complete or partial remission on month 6, 12 and 18

Time frame: 6, 12, 18 months after randomization

complete remission (CR) on 6, 12, 18, 24 month

complete remission on month 6, 12, 18 and 24

Time frame: 6, 12, 18, 24 months after randomization

Time to complete remission (CR) or partial remission (PR)

Time to complete or partial remission

Time frame: from date of randomization until the date of first remission, assessed up to 24 months

Change of estimated glomerular filtration rate (eGFR)

Change of eGFR from baseline to 24 months

Time frame: 24 months

Serum creatinine increase≥50 percent from baseline

proportion of patients with increase of serum creatinine ≥50 percent from baseline

Time frame: 24 months

Proportion of patients with relapse

Rate of relapse. Relapse is defined as development of nephrotic range proportion of patients with relapse. Relapse is defined as development of proteinuria\>3.5g/24h following CR or PR.

Data from ClinicalTrials.gov

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