- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04531865
Randomized Trial Evaluating Mycophenolate Mofetil in Children With Nephrotic Syndrome After Rituximab Treatment
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 Overview
Status
Intervention / Treatment
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 Type
Phase
- Phase 3
Contacts and Locations
Study Locations
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Shanghai, China
- Shanghai Children's Medical Center
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Shanghai, China
- Shanghai Children's Hospital
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Shanghai, China
- Xinhua Hospital, Shanghai Jiaotong University School of Medicine
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Shanghai
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Shanghai, Shanghai, China, 200000
- Children's Hospital of Fudan University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Rituximab and Mycophenolate Mofetil
First course Course Rituximab at Randomization.
Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards.
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Rituximab: 375 mg/m2 intravenously on day 0 and day 7
Other Names:
Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards.
Dose: 20~30mg/kg/day,BID.
Total duration : 8 months.
Other Names:
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Placebo Comparator: Rituximab Only
First course Course Rituximab at Randomization.
Addition of Maintenance Placebo tablets matching Mycophenolate mofetil from 4 Month onwards.
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Rituximab: 375 mg/m2 intravenously on day 0 and day 7
Other Names:
Addition of Maintenance Placebo tablets matching Mycophenolate Mofetil from 4 Month onwards.
Dose: 20~30mg/kg/day,BID.
Total duration : 8 months.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
1-year relapse-free survival rate
Time Frame: 1-year period after randomization
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The rate of no relapse within 1 year
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1-year period after randomization
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The concentration for MPA-area under curve(AUC)
Time Frame: At 48 weeks
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Blood concentrations of mycophenolic acid (MPA)
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At 48 weeks
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Proportion of patients with a relapse
Time Frame: 6 months period after randomization
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The proportion of patients with relapse
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6 months period after randomization
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Time to relapse (days)
Time Frame: 1-year period after randomization
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Number of days from randomization to occurrence of first relapse
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1-year period after randomization
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B-Cell Recovery Time
Time Frame: 1-year period after randomization
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Time to the first detection of CD19+ cells above 1% of total CD45+ lymphocytes after CD19+ cell depletion
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1-year period after randomization
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Change in growth velocity
Time Frame: 1-year period after randomization
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The standard deviation scores (SDS) for height at 12th month minus that of randomization.
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1-year period after randomization
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adverse events
Time Frame: 1-year period after randomization
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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)
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1-year period after randomization
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Xu Hong, PhD.MD., Children's Hospital of Fudan University
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Kidney Diseases
- Urologic Diseases
- Disease
- Syndrome
- Nephrotic Syndrome
- Nephrosis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antitubercular Agents
- Antibiotics, Antitubercular
- Rituximab
- Mycophenolic Acid
Other Study ID Numbers
- FRSDRM
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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