Clinical trial NCT04531865: Randomized Trial Evaluating Mycophenolate Mofetil in Children With Nephrotic Syndrome After Rituximab Treatment
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Frequently Relapsing Nephrotic Syndrome
Steroid-Dependent Nephrotic Syndrome
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
Collaborators: name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Shanghai Children's Medical Center
name: Shanghai Children's Hospital
First posted: 2020-08-31
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 1-year relapse-free survival rate
timeFrame: 1-year period after randomization
Secondary outcomes:
measure: The concentration for MPA-area under curve(AUC)
timeFrame: At 48 weeks
measure: Proportion of patients with a relapse
timeFrame: 6 months period after randomization
measure: Time to relapse (days)
timeFrame: 1-year period after randomization
measure: B-Cell Recovery Time
timeFrame: 1-year period after randomization
measure: Change in growth velocity
timeFrame: 1-year period after randomization
measure: adverse events
timeFrame: 1-year period after randomization
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children's hospital of Fudan university
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Children's Hospital
city: Shanghai
country: China
facility: Shanghai Children's Medical Center
city: Shanghai
country: China
facility: Xinhua Hospital, Shanghai Jiaotong University School of Medicine
Study officials:
affiliation: Children's Hospital of Fudan University
name: Xu Hong, PhD.MD.
role: PRINCIPAL_INVESTIGATOR
References: