Steroid-Sensitive Nephrotic SyndromePhase 2RTXFIRPedINSNCT04783675
Efficacy and Safety of Rituximab in the First Episode of Pediatric Idiopathic Nephrotic Syndrome
A Phase 2 study testing Rituximab in people with Steroid-Sensitive Nephrotic Syndrome, run by Children's Hospital of Fudan University at 8 sites in China.
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. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Steroid-Sensitive Nephrotic Syndrome
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 8 sitesChina
- Study dates
- 13 Apr 2021to 17 Jan 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
China8 sites
The First Affiliated Hospital of Zhongshan University
Guanzhou
Anhui Provincial Children's Hospital
Hefei, Anhui
Children's Hospital of Nanjing Medical University
Nanjing, Jiangsu
Shandong Provincial Hospital Affiliated to Shandong University
Shandong
Children's Hospital of Fudan University
Shanghai, 201102
Wuhan Children's Hospital,Tongji Medical College, Huazhong University of Science and Technology.
Wuhan, Hubei
Xuzhou Children's Hospital
Xuzhou
Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital
Zhengzhou, Henan
About this study
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.
Read the 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.
- Conditions
- Steroid-Sensitive Nephrotic Syndrome
- Being tested
- Rituximab
- Medical subject headings
- Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Rituximab (375 mg/m2) will be given as a single intravenous infusion after remission
| Study group | Role | What they receive |
|---|---|---|
| Intervention/treatment | Experimental | Not described Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year relapse-free survival rate
The rate of no relapse within 1 year
Measured: 1-year period after randomization
Secondary outcomes (5)
Time to relapse (days)
Number of days from randomization to occurrence of first relapse
Measured: 1-year period after administration of rituximab therapy
Proportion of patients with a relapse
The proportion of patients with relapse
Measured: 6 months period after administration of rituximab therapy
B-Cell Recovery Time
Time to the first detection of CD19+ cells above 1% of total CD45+ lymphocytes after CD19+ cell depletion
Measured: 1-year period after administration of rituximab therapy
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.
Measured: 1-year period after administration of rituximab therapy
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
Measured: 1-year period after administration of rituximab therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2021
- Study start13 Apr 2021
- Primary completion17 Jan 2023
- Study completion17 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Steroid-Sensitive Nephrotic SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital of Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Rituximab
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04783675
- Sponsor's protocol ID
- RTXFIRPedINS
- Acronym
- RTXFIRPedINS
- Status last verified
- Jul 2023
- First submitted
- 28 Feb 2021
- Last updated
- 11 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be available to researchers with a clear research plan and hypothesis, with the appropriate team in place to undertake the work.
Publications
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.
PubMed 36223961
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Rituximab in the First Episode of Pediatric Idiopathic Nephrotic Syndrome
- ClinicalTrials.gov ID
- NCT04783675
- Acronym / sponsor ID
- RTXFIRPedINS / RTXFIRPedINS
- Conditions
- Steroid-Sensitive Nephrotic Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Children's Hospital of Fudan UniversityUniversity, hospital or other
- Collaborators
- 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
- Study start
- 13 Apr 2021 (actual)
- Primary completion
- 17 Jan 2023 (actual)
- Study completion
- 17 Jan 2023 (actual)
- First posted
- 5 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Rituximab
| Arm | Type | Receives |
|---|---|---|
| Intervention/treatment | Experimental | Drug: Rituximab |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabRituximab (375 mg/m2) will be given as a single intravenous infusion after remission | Drug | Intervention/treatment |
Primary outcome
1-year relapse-free survival rate
Time frame: 1-year period after randomization
The rate of no relapse within 1 year
5 secondary outcomes
Time to relapse (days)
Time frame: 1-year period after administration of rituximab therapy
Proportion of patients with a relapse
Time frame: 6 months period after administration of rituximab therapy
B-Cell Recovery Time
Time frame: 1-year period after administration of rituximab therapy
The effect of rituximab on peripheral blood B cell subsets and T cell subsets to highlight biomarkers useful for monitoring response to rituximab treatment.
Time frame: 1-year period after administration of rituximab therapy
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 1-year period after administration of rituximab therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2023.
- Derived from this study: PubMed 36223961Liu 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.
- Individual participant dataSharing planned: Yes. Data will be available to researchers with a clear research plan and hypothesis, with the appropriate team in place to undertake the work.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Steroid-Sensitive Nephrotic Syndrome, run by Children's Hospital of Fudan University at 8 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year relapse-free survival rate (time frame: 1-year period after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04783675, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2023.