Rituximab in the First Episode of Paediatric Nephrotic Syndrome

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Primary Purpose

Status

Not yet recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Rituximab

Corticosteroid

About this trial

This is an interventional treatment trial for Steroid-Sensitive Nephrotic Syndrome focused on measuring Rituximab, Children, Relapse

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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) Estimated glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry Remission at study entry the cluster of differentiation antigen 20 (CD20) positive cells in peripheral blood ≥1% total lymphocytes No immunosuppressive agents have been used within 3 months of enrolment, except for the use of corticosteroid to treat nephrotic syndrome 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: Diagnosis of secondary NS Patients showing one of the following abnormal clinical laboratories 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 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 Live vaccination within last month Patients with poorly controlled hypertension Patients with severe brain, heart, liver, and other important organs, as well as blood and endocrine system diseases Presence or history of autoimmune diseases, primary immunodeficiency, or tumor Patients with a known allergy to Rituximab and its excipients 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)

Sites / Locations

Children's hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai's Children's Medical Center
Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Rituximab

Routine Therapy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

1-year relapse-free survival rate

The rate of no relapse within 1 year. Relapse definition: recurrence of nephrotic-range proteinuria, urine protein/creatinine ratio ≥2 mg/mg or dipstick ≥3+ on 3 consecutive days in the first morning samples.

Secondary Outcome Measures

Time to relapse (days)

Number of days from randomization to occurrence of first relapse. Relapse definition: recurrence of nephrotic-range proteinuria, urine protein/creatinine ratio ≥2 mg/mg or dipstick ≥3+ on 3 consecutive days in the first morning samples.

Peripheral blood T cell subsets

It is a repeat measured variable. Using fluorescence-activated cell sorting, peripheral blood T cells subsets will be studied as percentages and absolute counts.

Peripheral blood B cell subsets

It is a repeat measured variable. Using fluorescence-activated cell sorting, peripheral blood B cells subsets will be studied as percentages and absolute counts.

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

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

Full Information

NCT ID

NCT05850546

First Posted

April 28, 2023

Last Updated

August 29, 2023

Sponsor

Children's Hospital of Fudan University

Collaborators

Shanghai Shen Kang Hospital Development Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Children's Medical Center, Shanghai Children's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05850546

Brief Title

Rituximab in the First Episode of Paediatric Nephrotic Syndrome

Official Title

Efficacy and Safety of Single-dose Rituximab Biosimilar in the Initial Episode of Paediatric Steroid-sensitive Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

September 1, 2023 (Anticipated)

Primary Completion Date

November 30, 2025 (Anticipated)

Study Completion Date

December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Children's Hospital of Fudan University

Collaborators

Shanghai Shen Kang Hospital Development Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Children's Medical Center, Shanghai Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Steroid-Sensitive Nephrotic Syndrome

Keywords

Rituximab, Children, Relapse

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

138 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Rituximab

Arm Type

Experimental

Arm Description

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.

Arm Title

Routine Therapy

Arm Type

Other

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

rituximab biosimilar (HANLIKANG®, Shanghai Henlius Biotech, Inc. China)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Corticosteroid

Other Intervention Name(s)

prednisolone/prednisone

Intervention Description

guideline-recommended corticosteroid therapy

Primary Outcome Measure Information:

Title

1-year relapse-free survival rate

Description

The rate of no relapse within 1 year. Relapse definition: recurrence of nephrotic-range proteinuria, urine protein/creatinine ratio ≥2 mg/mg or dipstick ≥3+ on 3 consecutive days in the first morning samples.

Time Frame

1-year after randomization

Secondary Outcome Measure Information:

Title

Time to relapse (days)

Description

Number of days from randomization to occurrence of first relapse. Relapse definition: recurrence of nephrotic-range proteinuria, urine protein/creatinine ratio ≥2 mg/mg or dipstick ≥3+ on 3 consecutive days in the first morning samples.

Time Frame

1-year after randomization

Title

Peripheral blood T cell subsets

Description

It is a repeat measured variable. Using fluorescence-activated cell sorting, peripheral blood T cells subsets will be studied as percentages and absolute counts.

Time Frame

At basline, 1,3,6,9,12 months after randomization

Title

Peripheral blood B cell subsets

Description

It is a repeat measured variable. Using fluorescence-activated cell sorting, peripheral blood B cells subsets will be studied as percentages and absolute counts.

Time Frame

At basline, 1,3,6,9,12 months after randomization

Title

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Description

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

Time Frame

1-year after randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Estimated glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry Remission at study entry the cluster of differentiation antigen 20 (CD20) positive cells in peripheral blood ≥1% total lymphocytes No immunosuppressive agents have been used within 3 months of enrolment, except for the use of corticosteroid to treat nephrotic syndrome 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: Diagnosis of secondary NS Patients showing one of the following abnormal clinical laboratories 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 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 Live vaccination within last month Patients with poorly controlled hypertension Patients with severe brain, heart, liver, and other important organs, as well as blood and endocrine system diseases Presence or history of autoimmune diseases, primary immunodeficiency, or tumor Patients with a known allergy to Rituximab and its excipients 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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Qian Shen

Phone

+8602164932827

Email

shenqian@shmu.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Qian Shen

Organizational Affiliation

Children's Hospital of Fudan University

Official's Role

Study Chair

Facility Information:

Facility Name

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

City

Shanghai

State/Province

Shanghai

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yulin Kang

Facility Name

Shanghai's Children's Medical Center

City

Shanghai

State/Province

Shanghai

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lei Ying

Facility Name

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

City

Shanghai

State/Province

Shanghai

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yufeng Li

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data will be available to researchers with a clear research plan and hypothesis, with the appropriate team in place to undertake the work.

IPD Sharing Time Frame

When the article has been published with no end date

IPD Sharing Access Criteria

Requests for access to data from the RTXFIRPedINS2 trial should be addressed to the corresponding author at hxu@shmu.edu.cn. The individual participant data collected during the trial (including the data dictionary) will be available, after de-identification. All proposals requesting data access will need to have a research plan and specify how the data will be used, and all proposals will need the approval of the trial coinvestigator team (or individual(s) subsequently delegated this responsibility) before data release

Citations:

PubMed Identifier

36223961

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.

Results Reference

result

Steroid-Sensitive Nephrotic Syndrome

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial