Efficacy and Safety of Rituximab in the First Episode of Pediatric Idiopathic Nephrotic Syndrome (RTXFIRPedINS)

The main objective is to demonstrate, from the initial episode of nephrotic syndrome (NS) in children with standard prednisolone treatment, once complete remission has occurred, that the use of Rituximab (a single intravenous infusion of 375 mg/m2) may reduce the risk of subsequent relapse during 12-month of follow-up.

Study Overview

• Status: Completed
• Conditions: Steroid-Sensitive Nephrotic Syndrome
• Intervention / Treatment: Drug: Rituximab

Detailed Description

NS is the most frequent glomerular disease in children. Between 80% and 90% of children with steroid-sensitive nephrotic syndrome (SSNS) will relapse following an initial response to corticosteroids. Half of these children will experience frequent relapses (FRNS) or become steroid-dependent (SDNS).

The results of multiple observational studies and randomized control trials have shown that Rituximab, a chimeric monoclonal antibody against the cluster of differentiation antigen 20 (CD20) antigen on B cells, is safe and effective for children with FRNS/SDNS without corticosteroid or immunosuppressive therapy. To the investigators' knowledge, Rituximab has never been investigated for the initial episode of NS with the aim to reduce the subsequent risk of relapse that is a major concern in the management of children with NS.

Children aged 1-18 years with the first episode of the SSNS will be treated with a single intravenous infusion of Rituximab 375 mg/m2. The prednisolone at a dose of 2 mg/kg per day (maximum 60 mg in single or divided doses) for 6 weeks, followed by 1.5 mg/kg (maximum 40 mg) as a single morning dose on alternate days for the next 6 weeks; therapy is then discontinued.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xu Hong, PhD.MD.; Phone Number: +8602164932829; Email: hxu@shmu.edu.cn
• Study Contact Backup: Name: Shen qian, PhD.MD.; Phone Number: +8602164932827; Email: shenqian@shmu.edu.cn

Study Locations

• China
  • Guanzhou, China
    • The First Affiliated Hospital of Zhongshan University
  • Shandong, China
    • Shandong Provincial Hospital Affiliated to Shandong University
  • Shanghai, China, 201102
    • Children's Hospital of Fudan University
  • Xuzhou, China
    • Xuzhou Children's Hospital
  • Anhui
    • Hefei, Anhui, China
      • Anhui Provincial Children's Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Wuhan Children's Hospital,Tongji Medical College, Huazhong University of Science and Technology.
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Children's Hospital of Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Children between 1 and 18 years with Steroid-Sensitive Nephrotic Syndrome
• 2. Estimated glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry.
• 3. Remission at study entry
• 4.CD20 positive cells in peripheral blood ≥1% total lymphocytes
• 5.No immunosuppressive agents have been used within 3 months of enrollment, except for the use of corticosteroid to treat nephrotic syndrome.
• 6. Provision of consent by a legal representative (parents or legal guardians) using a document approved by the institutional review board after receiving an adequate explanation regarding the implementation of this clinical trial. For children/youth ages 10-18, written assent is required using age-appropriate and background-appropriate documents.

Exclusion Criteria:

• 1.Diagnosis of secondary NS
• 2.Patients showing one of the following abnormal clinical laboratory values: leukopenia (white blood cell count ≤3.0*109/L); moderate and severe anemia (hemoglobin <9.0g/dL); thrombocytopenia (platelet count <100*1012/ L); positivity of autoimmunity tests (ANA, Anti DNA antibody, ANCA) or reduced C3 levels; Positive for hepatitis B surface (HBs) antigen, HBs antibody, hepatitis B core (HBc) antibody, or hepatitis C virus (HCV) antibody ; Positive for HIV antibody; Alanine aminotransferase (ALT) > 2.5× upper limit of normal value. Aspartate aminotransferase (AST) > 2.5× upper limit of normal value.
• 3. Presence or history of severe or opportunistic infections within 6 months before assignment; Presence of active tuberculosis or with a history of tuberculosis or in whom tuberculosis is suspected; Presence or history of chronic active infections such as Epstein-Barr virus and CMV virus; presence or history of active hepatitis B or hepatitis C or hepatitis B virus carrier. Presence of human immunodeficiency virus (HIV) infection or other active viral infections
• 4. Receipt of a live vaccine within 4 weeks before enrollment.
• 5. Prior receipt of monoclonal antibodies of any type
• 6. History of angina pectoris, cardiac failure, myocardial infarction, or serious arrhythmia，or poorly controlled hypertension
• 7. Presence or history of autoimmune diseases or vascular purpura.
• 8. Presence or history of malignant tumor
• 9. History of organ transplantation (excluding corneal and hair transplants).
• 10. Patients with a known allergy to steroid and their excipients or to Rituximab and its excipients or to acetaminophen and its excipients or to cetirizine and its excipients or to the protein of murine origin
• 11. Assessed to be unfit for participation by the investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention/treatment	Drug: Rituximab; Rituximab (375 mg/m2) will be given as a single intravenous infusion after remission

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year relapse-free survival rate	The rate of no relapse within 1 year	1-year period after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to relapse (days)	Number of days from randomization to occurrence of first relapse	1-year period after administration of rituximab therapy
Proportion of patients with a relapse	The proportion of patients with relapse	6 months period after administration of rituximab therapy
B-Cell Recovery Time	Time to the first detection of CD19+ cells above 1% of total CD45+ lymphocytes after CD19+ cell depletion	1-year period after administration of rituximab therapy
The effect of rituximab on peripheral blood B cell subsets and T cell subsets to highlight biomarkers useful for monitoring response to rituximab treatment.	Using fluorescence-activated cell sorting (FACS), peripheral blood B cell subsets and T cell subsets will be measured as at baseline, before and after infusion of rituximab at 3,6,12 months, and when relapse.	1-year period after administration of rituximab therapy
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	It is a binary variable (1/0). The variable would be setted as "1" if any adverse events occurs including infusion-related reactions, infection (upper respiratory tract infection, hepatitis B virus reactivation, herpes zoster infection, pneumocystis pneumonia, etc), persistent hypogammaglobulinaemia, encephalopathy, severe neutropenia, fatal pulmonary fibrosis, ulcerative colitis, Crohn's disease and fulminant myocarditis etc. Adverse events will be graded according to the Common Terminology Criteria for Adverse Events	1-year period after administration of rituximab therapy

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Collaborators: Shandong Provincial Hospital; Wuhan Union Hospital, China; Children's Hospital of Nanjing Medical University; Anhui Provincial Children's Hospital; Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital; The first affiliated hospital of Zhongshan university; Xuzhou Children's Hospital

Publications and helpful links

General Publications

• Liu J, Shen Q, Xie L, Wang J, Li Y, Chen J, Fang X, Tang X, Qian B, Xu H. Protocol for an open-label, single-arm, multicentre clinical study to evaluate the efficacy and safety of rituximab in the first episode of paediatric idiopathic nephrotic syndrome. BMJ Open. 2022 Oct 12;12(10):e064216. doi: 10.1136/bmjopen-2022-064216.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Actual): January 17, 2023
• Study Completion (Actual): January 17, 2023

Study Registration Dates

• First Submitted: February 28, 2021
• First Submitted That Met QC Criteria: March 3, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 9, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Syndrome; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: RTXFIRPedINS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be available to researchers with a clear research plan and hypothesis, with the appropriate team in place to undertake the work.
• IPD Sharing Time Frame: When the article has been published with no end date
• IPD Sharing Access Criteria: Requests for access to data from the RTXFIRPedINS trial should be addressed to the corresponding author at hxu@shmu.edu.cn. The individual participant data collected during the trial (including the data dictionary) will be available, after de-identification. All proposals requesting data access will need to have a research plan and specify how the data will be used, and all proposals will need the approval of the trial coinvestigator team (or individual(s) subsequently delegated this responsibility) before data release.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No