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

Fudan University

Status and phase: Withdrawn; Phase 3

Conditions: Frequently Relapsing Nephrotic Syndrome; Steroid-Dependent Nephrotic Syndrome

Treatments: Drug: Mycophenolate Mofetil; Drug: Rituximab; Drug: Placebo tablets matching Mycophenolate Mofetil

Study type: Interventional

Funder types: Other

Identifiers

NCT04531865

FRSDRM

Details and patient eligibility

About

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

Full 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.

Sex: All

Ages: 1 to 16 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

Rituximab and Mycophenolate Mofetil

Experimental group

Description:

First course Course Rituximab at Randomization. Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards.

Treatment:

Drug: Mycophenolate Mofetil

Drug: Rituximab

Rituximab Only

Placebo Comparator group

Description:

First course Course Rituximab at Randomization. Addition of Maintenance Placebo tablets matching Mycophenolate mofetil from 4 Month onwards.

Treatment:

Drug: Rituximab

Drug: Placebo tablets matching Mycophenolate Mofetil