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

Primary Purpose

Steroid-Sensitive Nephrotic Syndrome

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Rituximab
Sponsored by
Children's Hospital of Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Steroid-Sensitive Nephrotic Syndrome

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention/treatment

Arm Description

Outcomes

Primary Outcome Measures

1-year relapse-free survival rate
The rate of no relapse within 1 year

Secondary Outcome Measures

Time to relapse (days)
Number of days from randomization to occurrence of first relapse
Proportion of patients with a relapse
The proportion of patients with relapse
B-Cell Recovery Time
Time to the first detection of CD19+ cells above 1% of total CD45+ lymphocytes after CD19+ cell depletion
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.
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

Full Information

First Posted
February 28, 2021
Last Updated
July 9, 2023
Sponsor
Children's Hospital of Fudan University
Collaborators
Children's Hospital of Nanjing Medical University, Wuhan Union Hospital, China, Anhui Provincial Children's Hospital, Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital, The first affiliated hospital of Zhongshan university, Shandong Provincial Hospital, Xuzhou Children's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04783675
Brief Title
Efficacy and Safety of Rituximab in the First Episode of Pediatric Idiopathic Nephrotic Syndrome
Acronym
RTXFIRPedINS
Official Title
Efficacy and Safety of Rituximab in the First Episode of Pediatric Idiopathic Nephrotic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
April 13, 2021 (Actual)
Primary Completion Date
January 17, 2023 (Actual)
Study Completion Date
January 17, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital of Fudan University
Collaborators
Children's Hospital of Nanjing Medical University, Wuhan Union Hospital, China, Anhui Provincial Children's Hospital, Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital, The first affiliated hospital of Zhongshan university, Shandong Provincial Hospital, Xuzhou Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Steroid-Sensitive Nephrotic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Rituximab
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention/treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab (375 mg/m2) will be given as a single intravenous infusion after remission
Primary Outcome Measure Information:
Title
1-year relapse-free survival rate
Description
The rate of no relapse within 1 year
Time Frame
1-year period after randomization
Secondary Outcome Measure Information:
Title
Time to relapse (days)
Description
Number of days from randomization to occurrence of first relapse
Time Frame
1-year period after administration of rituximab therapy
Title
Proportion of patients with a relapse
Description
The proportion of patients with relapse
Time Frame
6 months period after administration of rituximab therapy
Title
B-Cell Recovery Time
Description
Time to the first detection of CD19+ cells above 1% of total CD45+ lymphocytes after CD19+ cell depletion
Time Frame
1-year period after administration of rituximab therapy
Title
The effect of rituximab on peripheral blood B cell subsets and T cell subsets to highlight biomarkers useful for monitoring response to rituximab treatment.
Description
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.
Time Frame
1-year period after administration of rituximab therapy
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
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
Time Frame
1-year period after administration of rituximab therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Anhui Provincial Children's Hospital
City
Hefei
State/Province
Anhui
Country
China
Facility Name
Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital
City
Zhengzhou
State/Province
Henan
Country
China
Facility Name
Wuhan Children's Hospital,Tongji Medical College, Huazhong University of Science and Technology.
City
Wuhan
State/Province
Hubei
Country
China
Facility Name
Children's Hospital of Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
The First Affiliated Hospital of Zhongshan University
City
Guanzhou
Country
China
Facility Name
Shandong Provincial Hospital Affiliated to Shandong University
City
Shandong
Country
China
Facility Name
Children's Hospital of Fudan University
City
Shanghai
ZIP/Postal Code
201102
Country
China
Facility Name
Xuzhou Children's Hospital
City
Xuzhou
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
36223961
Citation
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.
Results Reference
derived

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

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