Clinical Study of Rituximab Combined With Corticosteroids or Rituximab Monotherapy in the Treatment of Primary Membranous Nephropathy

April 1, 2024 updated by: Wei Chen, First Affiliated Hospital, Sun Yat-Sen University

A Prospective, Randomized, Multicenter Clinical Trial Comparing the Efficacy and Safety of Rituximab Combined With Corticosteroids or Rituximab Monotherapy in Primary Membranous Nephropathy

This was a prospective, randomized, multicenter clinical trial. Seventy-eight patients with primary membranous nephropathy (PMN) were randomly divided into intervention or control group. Intervention group was given rituximab combined with corticosteroids in induction therapy and the control group was given rituximab monotherapy. After 6 months, patients who had decreased 24h urinary protein by > 25% but did not achieve CR were given rituximab maintenance therapy. The complete response rate at 12 months was measured.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study design A prospective, randomized , multicenter clinical study

Outcomes

  • Primary objective To evaluate the efficacy of rituximab combined with corticosteroids or rituximab monotherapy in primary membranous nephropathy
  • Secondary Objectives The safety of rituximab combined with corticosteroids or rituximab monotherapy in primary membranous nephropathy;

Primary outcome The complete response rate at 12 months;

  • Secondary outcomes

    1. Response rates at 6, 12, 18 and 24 months (including the proportion of participants with complete response and partial response);
    2. Median remission time;
    3. Proportion of patients without recurrence at 12, 18 and 24 months;
    4. Median non-recurrence time;
    5. Cumulative dose of glucocorticoids;
    6. CD19+ cell count, anti-PLA2R antibody expression level;
    7. Renal function index: eGFR;

    8. Incidence of adverse events;

      Study population Seventy-eight male or female treatment-naïve primary membranous nephropathy (PMN) patients

      Description of the study intervention Intervention group: rituximab combined with corticosteroids: 39 cases. Patients are pretreated with diphenhydramine and dexamethasone 30-60 minutes before rituximab infusion.

  • Induction therapy:

Rituximab intravenous infusion of 1g, d1, d15, combined with glucocorticoid therapy, oral prednisolone, initial dose of 0.5mg/(kg·d), once a day, after 8 weeks of treatment, reduce by 5mg every 4 weeks until 0.25mg/kg, this dose was maintained for 8 weeks, and then reduced by 2.5mg every 4 weeks, until 5-10mg is maintained, and the total course of treatment was about one year or so;

- Consolidation therapy after 6 months: Patients who achieve CR do not require consolidation therapy; Patients who had a 24-hour reduction in proteinuria >25% but did not achieve CR received an additional course of rituximab 1g, D1, D15 (independent of CD19+ cell count).

Patients with less than 25% decrease in proteinuria in 24 hours do not require continued medical therapy, and were considered as treatment failure and withdraw from the trial.

Control group: Rituximab monotherapy: 39 cases,

- Treatment regimen: 30-60 minutes before intravenous infusion of rituximab, diphenhydramine 20mg intramuscularly and dexamethasone 5mg intravenously were given for pretreatment.

  • Induction therapy:Rituximab intravenous infusion of 1g, d1, d15
  • Consolidation therapy after 6 months:

Patients who achieve CR do not require consolidation therapy; Patients who had a 24-hour reduction in proteinuria >25% but did not achieve CR received an additional course of rituximab 1g, D1, D15 (independent of CD19+ cell count).

Patients with less than 25% decrease in proteinuria in 24 hours do not require continued medical therapy, and were considered as treatment failure and withdraw from the trial.

The duration of the entire clinical study was 36 months from the date of project initiation.

Duration of visits: 2 years

Study Type

Interventional

Enrollment (Estimated)

78

Phase

  • Phase 4

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
    • Guangdong
      • Guangzhou, Guangdong, China, 510080

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

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Men and women aged 18-75 years;
  2. Patients diagnosed as primary membranous nephropathy (PMN) by renal biopsy;
  3. After treatment with ACE inhibitors or ARBs for at least 3 months, the following two points were met (unless intolerance to ACE inhibitors or ARBs, contraindications, hypotension that may cause side effects, or the investigator judged that the patient was not suitable for RAS inhibitors):

(1) Those who have an average 24-hour urine protein ≥ 3.5g twice a week, or an average 24-hour urine protein ≥ 5g twice in 14 days, the requirement of RASi for at least 3 months is not required (2) Blood pressure≤ 130/80mmHg, 4. Glomerular filtration rate (eGFR) ≥30mL/min/1.73m2 (calculated according to the CKD-EPI formula) 5. If female, must be postmenopausal or postoperatively infertile or on medical contraception (considering the potential risk of thromboembolism in patients with kidney disease); 6. Subjects voluntarily signed the informed consent form;

Exclusion Criteria:

  1. Patients with type 1 diabetes mellitus or type 2 diabetes mellitus complicated with diabetic nephropathy. Patients with a recent history of steroid-induced diabetes were eligible if renal biopsies show no evidence of secondary diabetic nephropathy within 6 months before the screening period
  2. Patients with secondary membranous nephropathy (such as hepatitis B and C, systemic lupus erythematosus, drug therapy, malignant tumors and other secondary causes);
  3. Previous treatment with rituximab, steroids, alkylating agents, calcineurin inhibitors, synthetic ACTH, mycophenolate (MMF), and azathioprine;
  4. Receipt of any other study medication (within the last month);
  5. Suspected or known allergy or immune reaction to rituximab, corticosteroids or any of their components (including excipients);
  6. Active infection, such as active hepatitis B or hepatitis C, tuberculosis (evidence of active tuberculosis infection within 1 year), or human immunodeficiency virus HIV infection (positive for anti-HIV antibodies), etc.
  7. A history of immunodeficiency, including other acquired or congenital immunodeficiency diseases, or organ transplantation;
  8. Females with a positive pregnancy screening test or lactating or planning to become pregnant in the next 24 months. Female or male patients who were unwilling to use contraceptive methods throughout the study;
  9. A history of mental illness;
  10. Laboratory tests that meet the following criteria need to be excluded:

(1) Hemoglobin<80g/L; (2) Platelet < 80×109/L; (3) Neutrophil <1.0×109/L; (4) Aspartate aminotransferase (AST) or amino aminotransferase (ALT) > 2.5× upper limit of normal except in relation to the primary disease; 11. Very high-risk patients: presenting with life-threatening nephrotic syndrome, or unexplained rapid deterioration of renal function 12. Any patient judged by the investigator to be unsuitable for inclusion in the trial.

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
Experimental: Intervention arm
rituximab combined with corticosteroids treatment group
Drug: rituximab combined with corticosteroids

Induction therapy:

Rituximab intravenous infusion of 1g, d1, d15, combined with glucocorticoid therapy, oral prednisolone, initial dose of 0.5mg/(kg·d), once a day, after 8 weeks of treatment, reduce by 5mg every 4 weeks until 0.25mg/kg, this dose was maintained for 8 weeks, and then reduced by 2.5mg every 4 weeks, until 5-10mg is maintained, and the total course of treatment was about one year or so;

Other Names:
  • Intervention arm
Active Comparator: Control arm
Rituximab monotherapy treatment
Drug: rituximab
Control group (treated with Rituximab monotherapy treatment) :Rituximab intravenous infusion of 1g, d1, d15
Other Names:
  • Control arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The complete response rate at 12 months;
Time Frame: 12 months
The complete response rate at 12 months;
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rates at 6, 12, 18 and 24 months (including the proportion of participants with complete response and partial response);
Time Frame: 24 months
Response rates at 6, 12, 18 and 24 months (including the proportion of participants with complete response and partial response);
24 months
Median remission time;
Time Frame: 24 months
Median remission time;
24 months
Proportion of patients without recurrence at 12, 18 and 24 months;
Time Frame: 24 months
Proportion of patients without recurrence at 12, 18 and 24 months;
24 months
Median non-recurrence time;
Time Frame: 24 months
Median non-recurrence time;
24 months
Cumulative dose of glucocorticoids;
Time Frame: 24 months
Cumulative dose of glucocorticoids;
24 months
CD19+ cell count, anti-PLA2R antibody expression level;
Time Frame: 24 months
CD19+ cell count, anti-PLA2R antibody expression level;
24 months
Renal function index: eGFR;
Time Frame: 24 months
Renal function index: eGFR;
24 months
Incidence of adverse events;
Time Frame: 24 months
Incidence of adverse events;
24 months

Collaborators and Investigators

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

Sponsor

First Affiliated Hospital, Sun Yat-Sen 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 (Estimated)

March 29, 2024

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

August 14, 2022

First Submitted That Met QC Criteria

August 22, 2022

First Posted (Actual)

August 24, 2022

Study Record Updates

Last Update Posted (Actual)

April 2, 2024

Last Update Submitted That Met QC Criteria

April 1, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HLK-202302

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

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.

Clinical Trials on Primary Membranous Nephropathy

Clinical Trials on rituximab combined with corticosteroids

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Iran

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe