Rituximab in the First Episode of Paediatric Nephrotic Syndrome

NCT ID: NCT05850546

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-01
• Study Completion Date: 2026-12-28

Brief Summary

The study will be a randomized, open-label trial in children with the initial episode of SSNS and whose state of complete remission after received standard prednisolone, to determine whether rituximab (a single intravenous infusion of 375 mg/m2) would be noninferior to corticosteroid alone in maintaining complete disease remission during 12-month of follow-up.

Detailed Description

The 12-month relapse-free survival rate is less than 30% in steroid-sensitive nephrotic syndrome (SSNS) children after the standard corticosteroid therapy, with approximately half becoming frequent relapsers or steroid dependent and necessitating the need for alternative immunosuppressive agents. The first relapse of SSNS most occurs within 6-12 months of onset, and contemporary cohorts suggest up to 16-42% of children with SSNS continue to have relapses in adulthood. Rituximab and rituximab biosimilar appear effective in reducing the relapse in children with frequent relapse or steroid dependent nephrotic syndrome. Accordingly, we hypothesize in paediatric SSNS, rituximab added to guideline-recommended corticosteroid therapy is noninferior to corticosteroid alone for maintaining remission for the first year of onset, expected to improve long-term outcomes.

An open-label, single-arm, multicentre trial was performed at eight centers in China with a 12-month follow-up (NCT04783675). The study found that in children with the initial episode of SSNS, rituximab appears to be an effective and safe treatment for maintaining disease remission.

The goal of this prospective study is to determine whether rituximab (a single intravenous infusion of 375 mg/m2) would be noninferior to corticosteroid alone in maintaining complete disease remission during 12-month of follow-up. The study will be a randomized, open-label, parallel group, in a 1:1 ratio, active controlled, multicenter trial.

Conditions

Steroid-Sensitive Nephrotic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab

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

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Rituximab 375 mg/m2 added to guideline-recommended corticosteroid therapy

Corticosteroid

Intervention Type: DRUG

guideline-recommended corticosteroid therapy

Routine Therapy

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.

Group Type: OTHER

Corticosteroid

Intervention Type: DRUG

guideline-recommended corticosteroid therapy

Interventions

Rituximab

Rituximab 375 mg/m2 added to guideline-recommended corticosteroid therapy

Intervention Type: DRUG

Corticosteroid

guideline-recommended corticosteroid therapy

Intervention Type: DRUG

Other Intervention Names

rituximab biosimilar (HANLIKANG®, Shanghai Henlius Biotech, Inc. China); prednisolone/prednisone

Eligibility Criteria

Inclusion Criteria

1. Children between 1 and 18 years with Steroid-Sensitive Nephrotic Syndrome (nephrotic-range proteinuria and either hypoalbuminemia or edema when albumin level is not available)

2. Estimated glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry

3. Remission at study entry

4. the cluster of differentiation antigen 20 (CD20) positive cells in peripheral blood ≥1% total lymphocytes

5. No immunosuppressive agents have been used within 3 months of enrolment, except for the use of corticosteroid to treat nephrotic syndrome

6. Provision of consent by a legal representative using a document approved by the institutional review board after receiving an adequate explanation of this clinical trial. For children ages 8-18, 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 laboratories

3. 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; Alanine aminotransferase or aspartate aminotransferase > 2.5× upper limit of normal value

4. Presence of severe or chronic infections within 6 months before assignment: tuberculosis or in whom tuberculosis is suspected; Epstein-Barr virus or cytomegalovirus; hepatitis B or hepatitis C or hepatitis B virus carrier, human immunodeficiency virus or other active viral infections

5. Live vaccination within last month

6. Patients with poorly controlled hypertension

7. Patients with severe brain, heart, liver, and other important organs, as well as blood and endocrine system diseases

8. Presence or history of autoimmune diseases, primary immunodeficiency, or tumor

9. Patients with a known allergy to Rituximab and its excipients

10. Assessed to be unfit for participation by the investigators (patients highly likely to be lost to follow-up or provide inaccurate data, for example, patients with alcohol or other substance misuse disorders, and patients with psychological disorders)

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Shanghai Shen Kang Hospital Development Center

OTHER

Sponsor Role: collaborator

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: collaborator

Shanghai Children's Medical Center

OTHER

Sponsor Role: collaborator

Shanghai Children's Hospital

OTHER

Sponsor Role: collaborator

Children's Hospital of Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Qian Shen

Role: STUDY_CHAIR

Children's Hospital of Fudan University

Locations

Children's hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Shanghai's Children's Medical Center

Shanghai, Shanghai Municipality, China

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Countries

China

Central Contacts

Qian Shen

Role: CONTACT

shenqian@shmu.edu.cn

+8602164932827

Facility Contacts

Yulin Kang

Role: primary

Lei Ying

Role: primary

Yufeng Li

Role: primary

References

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.

Reference Type: RESULT

PMID: 36223961 (View on PubMed)

Other Identifiers

RTXFIRPedINS2

Identifier Type: -

Identifier Source: org_study_id