Efficacy of Individualized Rituximab in Maintaining Remission of Moderate and Severe Systemic Lupus Erythematosus

A Multicenter, Randomized Controlled Clinical Study About Efficacy and Safety of Standard Dose and Individualized Dose of Rituximab in Maintaining Remission in Patients With Moderate to Severe Systemic Lupus Erythematosus

Several clinical studies have shown that rituximab is safe and effective for the induction of remission in moderate to severe systemic lupus erythematosus, and has been recommended by several guidelines for the induction of remission in refractory lupus with important organ involvement. However, there are few studies on the use of rituximab in the long-term maintenance and remission of the disease. There is no recognized scheme for the dose, interval and course of treatment of the drug. In this study, patients with moderate and severe systemic lupus erythematosus who achieved remission after standardized treatment were randomly divided into two groups at 1:1 and followed up every 3 months for 24 months. The basic situation and disease activity score of each subject were recorded. The recurrence rate of each observation group was calculated, the influencing factors of disease recurrence were analyzed, and a more reasonable drug use scheme was explored.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases
• Intervention / Treatment: Drug: Standard dose of rituximab; Drug: Individualized dose of rituximab

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jing Xue; Phone Number: 13858121751; Email: jingxue@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Second affiliated hospital of zhejiang university，school of medical
      • Contact: Jing Xue; Phone Number: 13858121751; Email: jingxue@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age, 18-65 years old, weight ≥ 40 kg, sex unlimited.
2. Clearly diagnosed with systemic lupus erythematosus.
3. There was at least one BILAG B or above score in the kidney, blood system and nervous system.
4. After standardized treatment with high dose glucocorticoid combined with immunosuppressants such as CTX,MMF or RTX, complete or partial remission of the disease was achieved (up to 1 BILAG B score, and at least 1 BILAG A or BILAG B score less than before).
5. Glucocorticoid: prednisone or the equivalent of prednisone less than or equal to 20 mg daily dose, and can be increased or decreased within 20 mg during the study.
6. Subjects are willing to participate in this study and sign informed consent voluntarily.
7. Prospective subjects agreed to use effective contraception throughout the study period.

Exclusion Criteria:

1. Abnormal liver function: ALT or AST >2ULN，or ALP or TBil >1.5ULN
2. Severe cardiopulmonary disease;
3. Severe blood system disease
4. Patient with malignant tumor;
5. Concurrent infection：Subjects were hospitalized for infection or treated with parenteral antibiotics within 30 days before random; Hepatitis B surface antigen positive or active hepatitis, not treated with hepatitis B antivirus; T-SPOT positive or active tuberculosis, not treated with antituberculous therapy; Any positive in HCV-Ab, HIV-Ab, or TPPA ;
6. Pregnant patients or patients with recent fertility requirements;
7. Received cyclophosphamide treatment within 30 days before random;
8. For any other reason, the investigator believes that it is inappropriate to participate in the trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard dose group	Drug: Standard dose of rituximab; Patients in this group will accept RTX 500mg treatment on the first day and on the 6th, 12th,18th and 24th month after that.
Experimental: Individualized dose group	Drug: Individualized dose of rituximab; Patients in this group will accept RTX 500mg treatment on the first day of admission. Patients will be followed-up every 3 months, and will receive one RTX 500mg treatment, if CD19 B cell count ≥ 1%, or dsDNA titer increased (dsDNA antibody positive, and increased more than 100% compared with the previous time), or complement C3 level decreased (lower than normal value, and decreased more than 50% compared with the previous time).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease recurrence rate within 24 months.	Evaluate the efficacy of individualized and standard dose rituximab in maintaining remission in moderate to severe SLE patients	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Times of use of rituximab in 2 years	24 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Yongmei Han, Sir Run Run Shaw Hospital; Principal Investigator: Hongzhi Wang, First Affiliated Hospital of Jiaxing University; Principal Investigator: Fei Han, Zhejiang University; Principal Investigator: Zhichun Liu, The second affiliated hospital of Suzhou University, school of medicine; Principal Investigator: Wenfeng Tan, The people's hospital of Jiangsu province; Principal Investigator: Xiudi Wu, The First Hospital of Ningbo; Principal Investigator: Hongwei Du, Jinhua Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 15, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: rituximab; Systemic lupus erythematosus
• Additional Relevant MeSH Terms: Immune System Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Autoimmune Diseases; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 2019-233

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