Back to resultsRandomized Trial Evaluating Mycophenolate Mofetil in Children With Nephrotic Syndrome After Rituximab Treatment
Primary Purpose
Frequently Relapsing Nephrotic Syndrome, Steroid-Dependent Nephrotic Syndrome
Status
Withdrawn
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Rituximab
Mycophenolate Mofetil
Placebo tablets matching Mycophenolate Mofetil
Sponsored by
About this trial
This is an interventional treatment trial for Frequently Relapsing Nephrotic Syndrome
Eligibility Criteria
Inclusion Criteria:
- Children between 1 and 16 years with Frequently-relapsing or Steroid-dependent Nephrotic Syndrome
- Estimated glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry.
- Remission at study entry
- Patients in whom ≥5 CD20-positive cells/μL are observed in the peripheral blood.
- Parents willing to give informed written and audiovisual consent.
Exclusion Criteria:
- Patients who have been diagnosed with nephritic- NS, such as immunoglobulin A(IgA) nephropathy, prior to assignment or in whom secondary NS is suspected.
- Patients showing one of the following abnormal clinical laboratory values:
1) Leukocytes < 3000/μL. 2) Neutrophils < 1500/μL. 3) Platelets < 50,000/μL. 4) Alanine aminotransferase (ALT) > 2.5× upper limit of normal value. 5) Aspartate aminotransferase (AST) > 2.5× upper limit of normal value. 6) Positive for hepatitis B surface (HBs) antigen, HBs antibody, hepatitis B core (HBc) antibody, or hepatitis C virus (HCV) antibody. 7) Positive for HIV antibody.
3. Patients meeting one of the following infection criteria:
1) Presence or history of severe infections within 6 months prior to assignment.2) Presence or history of opportunistic infections within 6 months prior to assignment.3) Presence of active tuberculosis.4) Patients with a history of tuberculosis or in whom tuberculosis is suspected.5) Presence or history of active hepatitis B or hepatitis C or hepatitis B virus carrier.6) Presence of human immunodeficiency virus (HIV) infection.
4. Presence or history of angina pectoris, cardiac failure, myocardial infarction, or serious arrhythmia (findings observed under Grade 4 of the Common Terminology Criteria for Adverse Events (CTCAE)).
5. Presence or history of autoimmune diseases or vascular purpura.
6. Presence or history of malignant tumor.
7. History of organ transplantation.
8. History of drug allergies to methylprednisolone, acetaminophen, cetirizine, mycophenolate mofetil,rituximab, or any of the above drugs
9. Uncontrollable hypertension.
10. Having received a live vaccine within 4 weeks prior to enrollment.
11. Patients who do not agree with contraception during the study period.
12. Judged inappropriate for this study by the treating or study physicians.
Sites / Locations
- Children's hospital of Fudan university
- Shanghai Children's Hospital
- Shanghai Children's Medical Center
- Xinhua Hospital, Shanghai Jiaotong University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Rituximab and Mycophenolate Mofetil
Rituximab Only
Arm Description
First course Course Rituximab at Randomization. Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards.
First course Course Rituximab at Randomization. Addition of Maintenance Placebo tablets matching Mycophenolate mofetil from 4 Month onwards.
Outcomes
Primary Outcome Measures
1-year relapse-free survival rate
The rate of no relapse within 1 year
Secondary Outcome Measures
The concentration for MPA-area under curve(AUC)
Blood concentrations of mycophenolic acid (MPA)
Proportion of patients with a relapse
The proportion of patients with relapse
Time to relapse (days)
Number of days from randomization to occurrence of first relapse
B-Cell Recovery Time
Time to the first detection of CD19+ cells above 1% of total CD45+ lymphocytes after CD19+ cell depletion
Change in growth velocity
The standard deviation scores (SDS) for height at 12th month minus that of randomization.
adverse events
It is a binary variable (1/0). The varibale would be setted as "1" if any adverse events occours including early infusion termination, acute infusion reaction Infection, pulmonary fibrosis, encephalopathy, neutropenia. Adverse events graded according to Common Terminology Criteria For Adverse Events (NCI-CTCAE v4.03)
Full Information
NCT ID
NCT04531865
First Posted
August 26, 2020
Last Updated
December 25, 2020
Sponsor
Children's Hospital of Fudan University
Collaborators
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
NCT04531865
Brief Title
Randomized Trial Evaluating Mycophenolate Mofetil in Children With Nephrotic Syndrome After Rituximab Treatment
Official Title
Efficacy and Safety of Mycophenolate Mofetil as Maintenance Therapy After Rituximab Treatment in Childhood-onset, Frequently-relapsing or Steroid-dependent Nephrotic Syndrome: a Multicenter Double-blind, Randomized, Placebo-controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Withdrawn
Why Stopped
lack of funding
Study Start Date
January 1, 2021 (Anticipated)
Primary Completion Date
September 1, 2022 (Anticipated)
Study Completion Date
October 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital of Fudan University
Collaborators
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
5. Study Description
Brief Summary
The aim of this study is to evaluate the efficacy and safety of maintenance Mycophenolate Mofetil following single course of Rituximab in maintaining remission over 12 months among Children with frequently-relapsing or steroid-dependent nephrotic syndrome
Detailed Description
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 complicated steroid-dependent/ frequently-relapsing nephrotic syndrome (SDFRNS) without corticosteroid or immunosuppressive therapy. Single rituximab infusion has been shown to be efficacious for 6 to 12 months, the reported median relapse-free period was 9 months. Our previous study found that Mycophenolate mofetil can further improve the sustained remission time.
All patients will be treated with 2 doses of Rituximab 375 mg/m2 iv at time 0 and 7 days. Addition of Maintenance Mycophenolate Mofetil or placebo from 4 Month onwards. The expected duration of the follow-up is 12 months, consisting of 12 visits.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Frequently Relapsing Nephrotic Syndrome, Steroid-Dependent Nephrotic Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab and Mycophenolate Mofetil
Arm Type
Experimental
Arm Description
First course Course Rituximab at Randomization. Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards.
Arm Title
Rituximab Only
Arm Type
Placebo Comparator
Arm Description
First course Course Rituximab at Randomization. Addition of Maintenance Placebo tablets matching Mycophenolate mofetil from 4 Month onwards.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituximab Biosimilar HLX01
Intervention Description
Rituximab: 375 mg/m2 intravenously on day 0 and day 7
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
Mycophenolate Mofetil Dispersible tablets（CYCOPIN®）
Intervention Description
Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards. Dose: 20~30mg/kg/day，BID. Total duration : 8 months.
Intervention Type
Drug
Intervention Name(s)
Placebo tablets matching Mycophenolate Mofetil
Intervention Description
Addition of Maintenance Placebo tablets matching Mycophenolate Mofetil from 4 Month onwards. Dose: 20~30mg/kg/day，BID. Total duration : 8 months.
Primary Outcome Measure Information:
Title
1-year relapse-free survival rate
Description
The rate of no relapse within 1 year
Time Frame
1-year period after randomization
Secondary Outcome Measure Information:
Title
The concentration for MPA-area under curve(AUC)
Description
Blood concentrations of mycophenolic acid (MPA)
Time Frame
At 48 weeks
Title
Proportion of patients with a relapse
Description
The proportion of patients with relapse
Time Frame
6 months period after randomization
Title
Time to relapse (days)
Description
Number of days from randomization to occurrence of first relapse
Time Frame
1-year period after randomization
Title
B-Cell Recovery Time
Description
Time to the first detection of CD19+ cells above 1% of total CD45+ lymphocytes after CD19+ cell depletion
Time Frame
1-year period after randomization
Title
Change in growth velocity
Description
The standard deviation scores (SDS) for height at 12th month minus that of randomization.
Time Frame
1-year period after randomization
Title
adverse events
Description
It is a binary variable (1/0). The varibale would be setted as "1" if any adverse events occours including early infusion termination, acute infusion reaction Infection, pulmonary fibrosis, encephalopathy, neutropenia. Adverse events graded according to Common Terminology Criteria For Adverse Events (NCI-CTCAE v4.03)
Time Frame
1-year period after randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Children between 1 and 16 years with Frequently-relapsing or Steroid-dependent Nephrotic Syndrome
Estimated glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry.
Remission at study entry
Patients in whom ≥5 CD20-positive cells/μL are observed in the peripheral blood.
Parents willing to give informed written and audiovisual consent.
Exclusion Criteria:
Patients who have been diagnosed with nephritic- NS, such as immunoglobulin A(IgA) nephropathy, prior to assignment or in whom secondary NS is suspected.
Patients showing one of the following abnormal clinical laboratory values:
1) Leukocytes < 3000/μL. 2) Neutrophils < 1500/μL. 3) Platelets < 50,000/μL. 4) Alanine aminotransferase (ALT) > 2.5× upper limit of normal value. 5) Aspartate aminotransferase (AST) > 2.5× upper limit of normal value. 6) Positive for hepatitis B surface (HBs) antigen, HBs antibody, hepatitis B core (HBc) antibody, or hepatitis C virus (HCV) antibody. 7) Positive for HIV antibody.
3. Patients meeting one of the following infection criteria:
1) Presence or history of severe infections within 6 months prior to assignment.2) Presence or history of opportunistic infections within 6 months prior to assignment.3) Presence of active tuberculosis.4) Patients with a history of tuberculosis or in whom tuberculosis is suspected.5) Presence or history of active hepatitis B or hepatitis C or hepatitis B virus carrier.6) Presence of human immunodeficiency virus (HIV) infection.
4. Presence or history of angina pectoris, cardiac failure, myocardial infarction, or serious arrhythmia (findings observed under Grade 4 of the Common Terminology Criteria for Adverse Events (CTCAE)).
5. Presence or history of autoimmune diseases or vascular purpura.
6. Presence or history of malignant tumor.
7. History of organ transplantation.
8. History of drug allergies to methylprednisolone, acetaminophen, cetirizine, mycophenolate mofetil,rituximab, or any of the above drugs
9. Uncontrollable hypertension.
10. Having received a live vaccine within 4 weeks prior to enrollment.
11. Patients who do not agree with contraception during the study period.
12. Judged inappropriate for this study by the treating or study physicians.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xu Hong, PhD.MD.
Organizational Affiliation
Children's Hospital of Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's hospital of Fudan university
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Facility Name
Shanghai Children's Hospital
City
Shanghai
Country
China
Facility Name
Shanghai Children's Medical Center
City
Shanghai
Country
China
Facility Name
Xinhua Hospital, Shanghai Jiaotong University School of Medicine
City
Shanghai
Country
China
12. IPD Sharing Statement
Learn more about this trial
Randomized Trial Evaluating Mycophenolate Mofetil in Children With Nephrotic Syndrome After Rituximab Treatment
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