Randomized Trial Evaluating Mycophenolate Mofetil in Children With Nephrotic Syndrome After Rituximab Treatment

Steroid-Dependent Nephrotic Syndrome Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04531865
• Other study ID #: FRSDRM
• Status: Withdrawn
• Phase: Phase 3
• Start date: January 1, 2021
• Est. completion date: October 1, 2022

Study information

• Verified date: December 2020
• Source: Children's Hospital of Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 1, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 16 Years

Eligibility

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.

Related Conditions & MeSH terms

• Frequently Relapsing Nephrotic Syndrome
• Nephrosis
• Nephrotic Syndrome
• Steroid-Dependent Nephrotic Syndrome
• Syndrome

Intervention

Drug:
• Rituximab
Rituximab: 375 mg/m2 intravenously on day 0 and day 7
• Mycophenolate Mofetil
Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards. Dose: 20~30mg/kg/day,BID. Total duration : 8 months.
• Placebo 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.

Locations

Country	Name	City	State
China	Children's hospital of Fudan university	Shanghai	Shanghai
China	Shanghai Children's Hospital	Shanghai
China	Shanghai Children's Medical Center	Shanghai
China	Xinhua Hospital, Shanghai Jiaotong University School of Medicine	Shanghai

Sponsors (4)

Lead Sponsor	Collaborator
Children's Hospital of Fudan University	Shanghai Children's Hospital, Shanghai Children's Medical Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year relapse-free survival rate	The rate of no relapse within 1 year	1-year period after randomization
Secondary	The concentration for MPA-area under curve(AUC)	Blood concentrations of mycophenolic acid (MPA)	At 48 weeks
Secondary	Proportion of patients with a relapse	The proportion of patients with relapse	6 months period after randomization
Secondary	Time to relapse (days)	Number of days from randomization to occurrence of first relapse	1-year period after randomization
Secondary	B-Cell Recovery Time	Time to the first detection of CD19+ cells above 1% of total CD45+ lymphocytes after CD19+ cell depletion	1-year period after randomization
Secondary	Change in growth velocity	The standard deviation scores (SDS) for height at 12th month minus that of randomization.	1-year period after randomization
Secondary	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)	1-year period after randomization