Steroid-Sensitive Nephrotic Syndrome
Conditions
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.
Interventions
DRUGRituximab
Rituximab (375 mg/m2) will be given as a single intravenous infusion after remission
Sponsors
Children's Hospital of Nanjing Medical University
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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 Hospital
Children's Hospital of Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Rituximab
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year relapse-free survival rate | 1-year period after randomization | The rate of no relapse within 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to relapse (days) | 1-year period after administration of rituximab therapy | Number of days from randomization to occurrence of first relapse |
| Proportion of patients with a relapse | 6 months period after administration of rituximab therapy | The proportion of patients with relapse |
| B-Cell Recovery Time | 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. | 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 | 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 |
Countries
China
Outcome results
None listed