Intervention: MONOMETHYL FUMARATE
Trial phase: Phase 3
SMILES: COC(=O)/C=C/C(=O)O
Sex: All
Age groups: Child | Adult
Healthy volunteers: No
Participants at risk: 3
Group description: Mycophenolate Mofetil will be continued in the patients in the MMF arm at a standard oral dose of 600 mg/m2 PO, BID starting on Study week 1 and continuing for 12 months

MMF: Subjects randomized to MMF, will continue MMF as scheduled by the investigator
Eligibility criteria:
Inclusion Criteria:

SDNS or FRNS
Complete remission, defined by absence of edema and 3 consecutive daily urine dipstick readings of trace or negative for protein
Must be taking MMF and have had at least one relapse while taking MMF in the prior 6 months that responded to corticosteroid treatment by re-entering complete remission at least 2 weeks prior to study entry.
BMI prior to onset of NS <99th percentile
Age 1-18 years
Estimated GFR >40 ml/min/1.73m² (by Modified Schwartz formula)
Negative serum pregnancy test (for females who are tanner stage 4 or 5)
Males and females of reproductive potential (sexually active in boys or post-menarche in girls) must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment

Exclusion Criteria:

• Prior therapy with rituximab, tacrolimus or cyclosporine

Prior therapy with cytotoxic agents in the past 90 days
History of genetic defects known to directly cause nephrotic syndrome (i.e. NPHS2 (podocin), NPHS1 (nephrin), PLCE1, WT1)
History of or concomitant severe, active infection (e.g. HIV, hepatitis B, hepatitis C)
History of diabetes mellitus
History of organ or bone marrow transplant
Secondary nephrotic syndrome (i.e. reflux nephropathy, IgA nephropathy, lupus nephritis, etc)
Live viral vaccines administered in the past 6 weeks (42 days)
Participation in another therapeutic trial within 30 days of enrollment
Allergy to study medications
ANC < 1.5 x 103
Hemoglobin: < 8.0 gm/dL
Platelets: < 100,000/mm
AST or ALT >2.5 x Upper Limit of Normal at the local institutions laboratory
Positive Hepatitis B or C serology (Hep B Surface antigen, Hep B Core antibody, and Hep C antibody)
History of HIV infection
Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
Receipt of a live vaccine within 4 weeks prior to randomization
Previous treatment with Natalizumab (Tysabri®)
Previous Treatment with Rituximab (Rituxan®)
Known hypersensitivity to Rituximab, to any of its excipients, or to murine proteins
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
History of recurrent significant infection or history of recurrent bacterial infections
Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
Lack of peripheral venous access
History of drug, alcohol, or chemical abuse within 6 months prior to screening
Pregnant, lactating, or refusal of birth control in an adolescent of child-bearing potential
Concomitant malignancies or previous malignancies
History of psychiatric disorder that would interfere with normal participation in this protocol
Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
Inability to comply with study and follow-up procedures

Patients who fail screening due to an abnormal laboratory parameter may be rescreened within the next 6 months if the local PI believes that the abnormality was transient and not related to a chronic underlying disease. Rescreening may only occur once and may not occur within 2 weeks of the initial screen failure.

If a patient has a clinically significant laboratory abnormality, the PI will be asked to define a follow-up plan (timing of repeating the laboratory test and/or additional work-up).