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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT04783675

Recruitment Status : Recruiting

First Posted : March 5, 2021

Last Update Posted : December 7, 2021

See Contacts and Locations

Sponsor:

Collaborators:

Children's Hospital of Nanjing Medical University

The Children's Hospital of Zhejiang University School of Medicine

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

Information provided by (Responsible Party):

Children's Hospital of Fudan University

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.

Condition or disease	Intervention/treatment	Phase
Steroid-Sensitive Nephrotic Syndrome	Drug: Rituximab	Phase 2

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 Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	44 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Intervention Model Description:	Rituximab
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Efficacy and Safety of Rituximab in the First Episode of Pediatric Idiopathic Nephrotic Syndrome
Actual Study Start Date :	April 13, 2021
Estimated Primary Completion Date :	March 24, 2023
Estimated Study Completion Date :	May 24, 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Congenital nephrotic syndrome

Drug Information available for: Rituximab

U.S. FDA Resources

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1-year relapse-free survival rate [ Time Frame: 1-year period after randomization ]
The rate of no relapse within 1 year

Secondary Outcome Measures :

Time to relapse (days) [ Time Frame: 1-year period after administration of rituximab therapy ]
Number of days from randomization to occurrence of first relapse
Proportion of patients with a relapse [ Time Frame: 6 months period after administration of rituximab therapy ]
The proportion of patients with relapse
B-Cell Recovery Time [ Time Frame: 1-year period after administration of rituximab therapy ]
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. [ Time Frame: 1-year period after administration of rituximab therapy ]
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 [ Time Frame: 1-year period after administration of rituximab therapy ]
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

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	1 Year to 18 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04783675

Contacts

Layout table for location contacts

Contact: Xu Hong, PhD.MD.	+8602164932829	hxu@shmu.edu.cn
Contact: Shen qian, PhD.MD.	+8602164932827	shenqian@shmu.edu.cn

Locations

Layout table for location information

China, Anhui
Anhui Provincial Children's Hospital	Recruiting
Hefei, Anhui, China
Contact: Deng Fang
Contact: Zhou huiqin
China, Henan
Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital	Recruiting
Zhengzhou, Henan, China
Contact: Liu Cuihua
China, Hubei
Wuhan Children's Hospital,Tongji Medical College, Huazhong University of Science and Technology.	Recruiting
Wuhan, Hubei, China
Contact: Wang Xiaowen
China, Jiangsu
Children's Hospital of Nanjing Medical University	Recruiting
Nanjing, Jiangsu, China
Contact: Zhang Aihua
China, Zhejiang
The Children's Hospital of Zhejiang University School of Medicine	Recruiting
Hangzhou, Zhejiang, China
Contact: Mao Jianhua
China
The First Affiliated Hospital of Zhongshan University	Recruiting
Guanzhou, China
Contact: Jiang Xiaoyun
Shandong Provincial Hospital Affiliated to Shandong University	Recruiting
Shandong, China
Contact: Sun Shuzheng
Children's Hospital of Fudan University	Recruiting
Shanghai, China, 201102
Contact: Xu Hong, PhD,MD +86-02164932829 hxu@shmu.edu.cn
Xuzhou Children's Hospital	Recruiting
Xuzhou, China
Contact: Zhang ruifeng

Sponsors and Collaborators