Clinical trial NCT04783675: Efficacy and Safety of Rituximab in the First Episode of Pediatric Idiopathic Nephrotic Syndrome
Official title: Efficacy and Safety of Rituximab in the First Episode of Pediatric Idiopathic Nephrotic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Steroid-Sensitive Nephrotic Syndrome
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Nanjing Medical University
name: Wuhan Union Hospital, China
name: Anhui Provincial Children's Hospital
name: Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital
name: The first affiliated hospital of Zhongshan university
name: Shandong Provincial Hospital
name: Xuzhou Children Hospital
First posted: 2021-03-05
Enrollment: 44
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Rituximab
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 1-year relapse-free survival rate
timeFrame: 1-year period after randomization
Secondary outcomes:
measure: Time to relapse (days)
timeFrame: 1-year period after administration of rituximab therapy
measure: Proportion of patients with a relapse
timeFrame: 6 months period after administration of rituximab therapy
measure: B-Cell Recovery Time
timeFrame: 1-year period after administration of rituximab therapy
measure: The effect of rituximab on peripheral blood B cell subsets and T cell subsets to highlight biomarkers useful for monitoring response to rituximab treatment.
timeFrame: 1-year period after administration of rituximab therapy
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 1-year period after administration of rituximab therapy
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Children's Hospital
state: Anhui
city: Zhengzhou
country: China
facility: Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital
state: Henan
city: Wuhan
country: China
facility: Wuhan Children's Hospital,Tongji Medical College, Huazhong University of Science and Technology.
state: Hubei
city: Nanjing
country: China
facility: Children's Hospital of Nanjing Medical University
state: Jiangsu
city: Guanzhou
country: China
facility: The First Affiliated Hospital of Zhongshan University
city: Shandong
country: China
facility: Shandong Provincial Hospital Affiliated to Shandong University
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
city: Xuzhou
country: China
facility: Xuzhou Children's Hospital
Study officials:
References:
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.