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

May 16, 2021 updated by: Peking Union Medical College Hospital

A Multicenter Randomized Controlled Trial of Rituximab Combined With Cyclosporine Versus Rituximab Alone in the Treatment of Idiopathic Membranous Nephropathy

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

126

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100730
        • Recruiting
        • Peking Union Medical College Hospital
      • Beijing, Beijing, China, 100037
        • Not yet recruiting
        • Fuwai Hospital, Chinese Academy of Medical Sciences
        • Contact:
          • Jianfang Cai
      • Beijing, Beijing, China, 100730
        • Not yet recruiting
        • Beijing Tongren Hospital, Capital Medical University
      • Beijing, Beijing, China, 101149
        • Not yet recruiting
        • Beijing Luhe Hospital, Capital Medical University
        • Contact:
          • Zhongxin Li
    • Henan
      • Nanyang, Henan, China, 473065
        • Not yet recruiting
        • Nanyang Nanshi Hospital, Henan University
        • Contact:
          • Mingwei Zhu
    • Shenzhen
      • Shenzhen, Shenzhen, China
        • Not yet recruiting
        • The Seventh Affiliated Hospital, Sun Yat-sen University
        • Contact:
          • Zhihua Zheng
    • Xinjiang
      • Urumqi, Xinjiang, China, 830054
        • Not yet recruiting
        • The First Affiliated Hospital of Xinjiang Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Rituximab monotherapy
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.
Drug: Rituximab
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.
Other Names:
  • CD20 antibody
Experimental: Rituximab combined with cyclosporine

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.
Drug: Rituximab
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.
Other Names:
  • CD20 antibody
Drug: cyclosporine
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.
Other Names:
  • CsA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
complete remission (CR) or partial remission (PR) at 24 month
Time Frame: 24 months after randomization
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
24 months after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
complete remission (CR) or partial remission (PR) on 6 month, 12 month, 18 month
Time Frame: 6, 12, 18 months after randomization
complete or partial remission on month 6, 12 and 18
6, 12, 18 months after randomization
complete remission (CR) on 6, 12, 18, 24 month
Time Frame: 6, 12, 18, 24 months after randomization
complete remission on month 6, 12, 18 and 24
6, 12, 18, 24 months after randomization
Time to complete remission (CR) or partial remission (PR)
Time Frame: from date of randomization until the date of first remission, assessed up to 24 months
Time to complete or partial remission
from date of randomization until the date of first remission, assessed up to 24 months
Change of estimated glomerular filtration rate (eGFR)
Time Frame: 24 months
Change of eGFR from baseline to 24 months
24 months
Serum creatinine increase≥50 percent from baseline
Time Frame: 24 months
proportion of patients with increase of serum creatinine ≥50 percent from baseline
24 months
Proportion of patients with relapse
Time Frame: 12，18，24 months
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.
12，18，24 months
Anti-PLA2R titer
Time Frame: baseline and 3, 6, 9, 12, 18, 24 months
Auto-antibodies to the M-type phospholipase A2 receptor(PLA2R)
baseline and 3, 6, 9, 12, 18, 24 months
The number of CD19+B cells
Time Frame: baseline and 3, 6, 9, 12, 18, 24 months
CD19+ B cells
baseline and 3, 6, 9, 12, 18, 24 months
Quality of life measured by kidney disease and quality of life (KDQOL-36)
Time Frame: baseline, 12 and 24 month
KDQOL-36 includes 36 questions which are scored positively (higher score indicating better quality of life) on a 0-100 scale using developer-recommended scoring.
baseline, 12 and 24 month
Adverse events
Time Frame: through study completion until 24 months
adverse events
through study completion until 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Beijing Tongren Hospital
Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
Chinese Academy of Medical Sciences, Fuwai Hospital
The Luhe Teaching Hospital of the Capital Medical University
The Seventh Affiliated Hospital of Sun Yat-sen University
First Affiliated Hospital of Xinjiang Medical University
Nanyang Nanshi Hospital of Henan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 14, 2021

Primary Completion (Anticipated)

March 1, 2023

Study Completion (Anticipated)

March 1, 2025

Study Registration Dates

First Submitted

January 30, 2021

First Submitted That Met QC Criteria

February 4, 2021

First Posted (Actual)

February 8, 2021

Study Record Updates

Last Update Posted (Actual)

May 18, 2021

Last Update Submitted That Met QC Criteria

May 16, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • iMN RTX plus CsA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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