Mycophenolate mofetil for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicenter, double-blind, randomised, placebo-controlled trial

Phase 3

• Conditions: Childhood-onset, complicated, frequently relapsing nephrotic syndrome / Steroid-dependent nephrotic; nephrotic syndrome

• Registration Number: JPRN-jRCTs051180081
• Lead Sponsor: ozu Kandai

Brief Summary

The median treatment failure-free period was longer in the MMF group than in the placebo group (throughout the observation and follow-up periods; HR: 0.593, 95% CI: 0.336 -1.049, Log-rank test: P=0.0694) (limited to the observation period; HR: 0.202, 95% CI: 0.081-0.503, Log-rank test: P=0.0001) The frequency and severity of adverse events were similar in both groups. MMF after rituximab may prevent developing FRNS/SDNS again, especially during MMF administration, and is well tolerated.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-02-27
• Study Completion: 2019-11-27
• Results First Posted: 2021-12-08
• Last Update Posted: 17 October 2023

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

1. Diagnosed as idiopathic nephrotic syndrome (INS) according to the ISKDC criteria.
2. The first onset of INS is between 1 - 18 years of age, and 2 years of age or older at assignment.
3. Patients meeting either one of the following criteria:
1) Diagnosed with frequent relapse or steroid dependence and once again diagnosed with frequent relapse or steroid dependence after completion of immunosuppressive drug therapy (cyclosporine, cyclophosphamide, or mizoribine, etc.).
2) Diagnosed with frequent relapse or steroid dependence and once again diagnosed with frequent relapse or steroid dependence during immunosuppressive drug therapy (cyclosporine, cyclophosphamide, or mizoribine, etc.).
3) Diagnosed with steroid resistance following the onset of INS anf diagnosed with frequent relapse or steroid dependence after the completion of immunosuppressive drug therapy (cyclosporine alone or combination of cyclosporine and methylprednisolone, etc.).
4) Diagnosed with steroid resistance following the onset of INS anf diagnosed with frequent relapse or steroid dependence during the immunosuppressive drug therapy (cyclosporine alone or combination of cyclosporine and methylprednisolone, etc.).
4. Patients with records of nearest preceding 3 relapses.
5. Patients in whom steroid sensitivity is observed during treatment of relapse immediately prior to assignment.
6. Patients in whom 5/microL or more CD20-positive cells are observed in the peripheral blood.
7. Patients who can be hospitalized overnight on the first day of rituximab administration.
8. Patients with written informed consent.

Exclusion Criteria

1. Patients who have been diagnosed with nephritic-NS, such as IgA nephropathy prior to assignment or in whom secondary NS is suspected.
2. Patients who used past monoclonal antibodies other than rituximab (regardless of mouse, rat, chimeric, human)
3. Patients meeting either one of the following infection:
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 HIV infection.
4. Presence or history of angina pectoris, cardiac failure, myocardial infarction, or serious arrhythmia (findings observed under Grade 4 of the CTCAE v4.0-JCOG.
5. Presence or history of auto-immune diseases or vascular purpura.
6. Presence or history of malignant tumor.
7. History of organ transplantation.
8. History of drug allergies to methylprednisolone, acetaminophen, or d-chlorpheniramine maleate.
9. Uncontrollable hypertension.
10. Deteriorated kidney function, e.g. estimated GFR<60 mL/min./1.73m2.
11. Having received a live vaccine within 4 weeks prior to enrollment.
12.Patients showing either one of the following abnormal clinical laboratory value:
1) WBC <3,000/microL.
2) neutrophil <1,500/microL.
3) PLT <50,000/microL.
4) ALT >2.5 x upper limit of normal value.
5) AST >2.5 x upper limit of normal value.
6) Positive for HBs antigen, HBs antibody, HBc antibody and HCV antibody.
7) Positive for HIV antibody.
13. Patients who do not agree with contraception during the study period.
14. Women during pregnancy or breast-feeding.
15. Judged inappropriate for this study by the physicians.

Study & Design

• Study Type: Interventional
• Study Design: Not specified