Frequently Relapsing Nephrotic Syndrome, Steroid-Dependent Nephrotic Syndrome
Conditions
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.
Interventions
DRUGRituximab
Rituximab: 375 mg/m2 intravenously on day 0 and day 7
DRUGMycophenolate Mofetil
Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards. Dose: 20\ 30mg/kg/day，BID. Total duration : 8 months.
DRUGPlacebo tablets matching Mycophenolate Mofetil
Addition of Maintenance Placebo tablets matching Mycophenolate Mofetil from 4 Month onwards. Dose: 20\ 30mg/kg/day，BID. Total duration : 8 months.
Sponsors
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai Children's Medical Center
Shanghai Children's Hospital
Children's Hospital of Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
1. Children between 1 and 16 years with Frequently-relapsing or Steroid-dependent Nephrotic Syndrome 2. Estimated glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry. 3. Remission at study entry 4. Patients in whom ≥5 CD20-positive cells/μL are observed in the peripheral blood. 5. Parents willing to give informed written and audiovisual consent.
Exclusion criteria
1. Patients who have been diagnosed with nephritic- NS, such as immunoglobulin A(IgA) nephropathy, prior to assignment or in whom secondary NS is suspected. 2. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year relapse-free survival rate | 1-year period after randomization | The rate of no relapse within 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The concentration for MPA-area under curve(AUC) | At 48 weeks | Blood concentrations of mycophenolic acid (MPA) |
| Proportion of patients with a relapse | 6 months period after randomization | The proportion of patients with relapse |
| Change in growth velocity | 1-year period after randomization | The standard deviation scores (SDS) for height at 12th month minus that of randomization. |
| B-Cell Recovery Time | 1-year period after randomization | Time to the first detection of CD19+ cells above 1% of total CD45+ lymphocytes after CD19+ cell depletion |
| adverse events | 1-year period after randomization | 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 to relapse (days) | 1-year period after randomization | Number of days from randomization to occurrence of first relapse |
Countries
China
Outcome results
None listed