Different Immunosuppressive Treatment in iMN

April 18, 2022 updated by: Peking Union Medical College Hospital

Different Immunosuppressive Treatment in Idiopathic Membranous Nephropathy: a Prospective Cohort

The primary objective of this study is to compare the 24 month remission of different immunosuppressive therapies in the treatment of idiopathic membranous nephropathy (iMN)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

To date, the first-line immunosuppressive immunosuppressive therapy of iMN includes corticosteroids combined with cyclophosphamide or rituximab (RTX). In recent randomized trials (MENTOR, GEMRITUX), the long-term remission rate of RTX is about 60%, which is similar to the remission rate of cyclophosphamide combined with corticosteroids in early studies. But there is only one published randomized trial (STARMEN) comparing the efficacy of the two protocols head-to-head. In STRAMEN trial, the long-term remission rate of cyclophosphamide+corticosteroids group was 83%, which was significantly higher than the that (58%) of the tacrolimus-RTX group. But in STRAMEN trial, only one single dose of RTX was given which might influence the efficacy of the tacrolimus-RTX arm. Therefore, head-to-head comparison of RTX (more than one dose) and cyclophosphamide+corticosteroid is needed. The optimal dose of RTX in the treatment of iMN is unclear. In MENTOR trial, RTX was given 1g on D1 and D15, and the rate of complete remission at 6 month was 0, so RTX was repeated at 6 month. Based on the experience of our center, most patients need at least one repeated dose of RTX at 6 month.

Based on the previous rationale, the investigators designed this study to compare the efficacy of cyclophosphamide plus corticosteroids with RTX in the treatment of iMN.

Study Type

Interventional

Enrollment (Anticipated)

200

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 Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100730

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 membranous nephropathy
  • Female, must be post-menopausal, sterile or have effective contraception
  • must be off steroid or mycophenolate mofetil for >1 month and alkylating agents for or RTX> 6 months
  • Angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for ≥ 3 months with controlled blood pressure prior to beginning of immunosuppressive therapy or if patients are intolerant to ACEI/ARB.
  • proteinuria ≥4g/24h and decreased ≤ 50% from baseline

Exclusion Criteria:

  • presence of active infection or a secondary cause of membranous nephropathy
  • proteinuria associated with diabetic nephropathy
  • pregnancy or breast feeding
  • history of resistance to rituximab or alkylating agents or corticosteroid
  • Patients who previously achieved remission after treatment of rituximab or alkylating agents but relapsed off rituximab 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: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: cyclophosphamide and prednisone

Prednisone will be given at 1mg/kg/d p.o. and will be tapered after 2 months and discontinued over a 6-12 month period.

Cyclophosphamide will be given at 1-2mg/kg/d p.o. with a target accumulated dose of 12g.

Azathioprine or mycophenolate mofetil are optional which could be given for a short period of time (<6 months）after discontinuation of cyclophosphamide if patients do not remit at 6 month.
Drug: Prednisone
1mg/kg/d p.o.which will be tapered after 2 months and discontinued over a 6-12 month period.
Drug: Cyclophosphamide
1-2mg/kg/d p.o. with a target accumulated dose of 12g.
Other Names:
  • CTX
ACTIVE_COMPARATOR: Rituximab

Rituximab 1000mg I.V. on Day1 and at 6 month. After 6 months, in patients with response but without complete remission, Rituximab could be stopped or repeated with a 6 month-interval (12 month, 18 month, 24 month) until complete remission. Rituximab 1000mg I.V. will be given on the 15th day after each Rituximab infusion if CD19+ B cell count>5/ul on the 15th day.

Calcineurin inhibitors (CNI) are optional but should be tapered after 6 months and discontinued after 9 months.
Drug: Rituximab
1000mg I.V. on D1 and at 6 month. After 6 month, in patients with response but not complete remission, Rituximab could be stopped or repeated with a 6 month-interval (12 month, 18 month, 24 month) until complete remission. Rituximab 1000mg I.V. will be repeated on the 15th day of each Rituximab infusion if CD19+ B cell count>5/ul.
Other Names:
  • CD20 antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
complete or partial remission on 24 month
Time Frame: 24 months
Complete remission is defined as urine protein < 0.5g/24h and serum albumin≥ 3.5g/dl. Partial remission is defined as reduction in urine protein≥50% plus urine protein ≤3.5g/24h but >0.5g/24h
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
complete or partial remission on 6, 12 and 18 month
Time Frame: 6, 12 and 18 months
complete or partial remission on 6, 12 and 18 month
6, 12 and 18 months
complete remission on 6, 12, 18 and 24 month
Time Frame: 6, 12, 18 and 24 months
complete remission on 6, 12, 18 and 24 month
6, 12, 18 and 24 months
time to complete or partial remission
Time Frame: from date of treatment until the date of first documented remission, up to 24 months
time to complete or partial remission
from date of treatment until the date of first documented remission, up to 24 months
change of estimated glomerular filtration rate (eGFR)
Time Frame: 24 months
change of estimated glomerular filtration rate (eGFR) from baseline
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
rate of relapse
Time Frame: 12, 18, 24 months
proportion of patients with relapse. Relapse is defined as development of urine protein >3.5g/24h following complete or partial remission.
12, 18, 24 months
anti-PLA2R levels
Time Frame: baseline and 3, 6, 9, 12, 18, 24 months
Auto-antibody to the M-type phospholipase A2 receptor (PLA2R)
baseline and 3, 6, 9, 12, 18, 24 months
CD19+ B cell count
Time Frame: baseline and 3, 6, 9, 12, 18, 24 months
CD19+ B cell count
baseline and 3, 6, 9, 12, 18, 24 months
Adverse events
Time Frame: through the study completion until 24 months
Adverse events
through the 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

Investigators

  • Principal Investigator: Yan Qin, Peking Union Medical College Hospital

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, 2025

Study Completion (ANTICIPATED)

March 1, 2027

Study Registration Dates

First Submitted

February 4, 2021

First Submitted That Met QC Criteria

February 4, 2021

First Posted (ACTUAL)

February 9, 2021

Study Record Updates

Last Update Posted (ACTUAL)

April 20, 2022

Last Update Submitted That Met QC Criteria

April 18, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • iMN cohort

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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