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
Trial Snapshot
- Phase
- Phase 3
- Status
- Withdrawn
- Locations
- 4
- Primary Endpoint
- 1-year relapse-free survival rate
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 1 Year to 16 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •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.
- •Patients meeting one of the following infection criteria:
- •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.
- •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)).
- •Presence or history of autoimmune diseases or vascular purpura.
- •Presence or history of malignant tumor.
- •History of organ transplantation.
- •History of drug allergies to methylprednisolone, acetaminophen, cetirizine, mycophenolate mofetil,rituximab, or any of the above drugs
- •Uncontrollable hypertension.
- •Having received a live vaccine within 4 weeks prior to enrollment.
- •Patients who do not agree with contraception during the study period.
- •Judged inappropriate for this study by the treating or study physicians.
Arms & Interventions
Rituximab and Mycophenolate Mofetil
First course Course Rituximab at Randomization. Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards.
Intervention: Rituximab (Drug)
Rituximab and Mycophenolate Mofetil
First course Course Rituximab at Randomization. Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards.
Intervention: Mycophenolate Mofetil (Drug)
Rituximab Only
First course Course Rituximab at Randomization. Addition of Maintenance Placebo tablets matching Mycophenolate mofetil from 4 Month onwards.
Intervention: Rituximab (Drug)
Rituximab Only
First course Course Rituximab at Randomization. Addition of Maintenance Placebo tablets matching Mycophenolate mofetil from 4 Month onwards.
Intervention: Placebo tablets matching Mycophenolate Mofetil (Drug)
Outcomes
Primary Outcomes
1-year relapse-free survival rate
Time Frame: 1-year period after randomization
The rate of no relapse within 1 year
Secondary Outcomes
- Time to relapse (days)(1-year period after randomization)
- B-Cell Recovery Time(1-year period after randomization)
- Change in growth velocity(1-year period after randomization)
- The concentration for MPA-area under curve(AUC)(At 48 weeks)
- Proportion of patients with a relapse(6 months period after randomization)
- adverse events(1-year period after randomization)