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

Steroid-Sensitive Nephrotic Syndrome Clinical Trial

— RTXFIRPedINS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04783675
• Other study ID #: RTXFIRPedINS
• Status: Completed
• Phase: Phase 2
• Start date: April 13, 2021
• Est. completion date: January 17, 2023

Study information

• Verified date: July 2023
• Source: Children's Hospital of Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 17, 2023
• Est. primary completion date: January 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Nephrosis
• Nephrotic Syndrome
• Steroid-Sensitive Nephrotic Syndrome
• Syndrome

Intervention

Drug:
• Rituximab
Rituximab (375 mg/m2) will be given as a single intravenous infusion after remission

Locations

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

Sponsors (8)

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year relapse-free survival rate	The rate of no relapse within 1 year	1-year period after randomization
Secondary	Time to relapse (days)	Number of days from randomization to occurrence of first relapse	1-year period after administration of rituximab therapy
Secondary	Proportion of patients with a relapse	The proportion of patients with relapse	6 months period after administration of rituximab therapy
Secondary	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
Secondary	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
Secondary	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