Fixed-dose Versus Concentration-controlled Mycophenolate Mofetil for the Treatment of Active Lupus Nephritis

Recruitment & Eligibility

Inclusion Criteria

Age 18-65 year
Diagnosis of SLE according to ACR criteria. At least 4 criteria must have been present for the diagnosis of SLE
Active lupus nephritis (both new and flare patients can be included) defined as:
- Within 16 weeks of randomization, had Biopsy-proven ISN class III or IV [exclude III(c), IV-S(c) and IV-G(c). Patients are permitted to have co-existing class V and
- At screening day, has urine protein creatinine ratio (UPCR) or 24-hour urinary protein ≥ 1.0 g/g or g/day

Exclusion Criteria

Pregnancy or breast feeding
Child-bearing age women who refuse to use effective birth-control
Poor compliance
Estimated-GFR < 20 mL/min/1.73 m2
Crescentic glomeruli more than 30 percent
Severe extra-renal involvement of SLE
History of severe allergic reactions or adverse effects to MMF
Uncontrolled concomitant disease
Known active, clinically significant infection of any kind
History of serious recurrent or chronic infection
History of malignancy (except basal cell carcinoma, squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been excised and cured)
Concomitant conditions which has required treatment with systemic corticosteroid (excluding topical or inhaled steroids) at any time in the 52 weeks prior to screening
Treatment with more than 1 g cyclophosphamide within the past 24 weeks
Receipt more than 3 g of IV pulse methylprednisolone within the past 12 weeks
Receipt prednisolone more than 30 mg/day for longer than 30 days within the past 12 weeks
Treatment with MMF at ≥ 1.5 g/day for over 4 weeks within the past 12 weeks
On treatment with Tacrolimus or Cyclosporine on the day of screening
Treatment with any biologic B-cell depleting therapy (e.g. anti CD-20, anti CD 22) within 52 weeks
Receiving concomitant medication interfering PK of MPA
- Cholestyramine
- Rifampin

Study & Design

Arm && Interventions

Group	Intervention	Description
FD arm	Mycophenolate Mofetil	MMF will be prescribed at a starting dose of 1.5 g/day and increased to 2 g/day at week 4 (if body weight ≥ 45 kg) and continue the same dose until week 24. After week 24, MMF will be lowered to 1.5 g/day.
CC Arm	Mycophenolate Mofetil	MMF will be prescribed at a starting dose of 1.5 g/day. MPA-C0 (trough) level will be measured weekly and MMF dose will be increased by 500 mg/day every week until the MPA-C0 level ≥ 3 mg/L or the MMF dosage is 3000 mg/day. After achieving the targeted MPA-C0 level, the MMF dose adjustment will be allowed only if the MPA-C0 levels are lower than 3 mg/L for two consecutive monitoring visits. After week 12, MMF will be maintained at the same dose until week 48

Primary Outcome Measures

Name	Time	Method
Response rate at 48 week of therapy	48 weeks

Secondary Outcome Measures

Name	Time	Method
C3 levels	48 weeks
Anti-dsDNA	48 weeks
eGFR at 96, 144 and 240 week	96, 144 and 240 weeks
MPA-area under the curve (AUC) 0-4 hour at 12 week	12 weeks
Urine IP-10 levels	48 weeks
Relapse free survival at 96, 144 and 240 week	96, 144 and 240 weeks
Adverse events	48 weeks
Mycophenolic acid trough levels	48 weeks
Progression to CKD stage 3 or more at 96, 144 and 240 week	96, 144 and 240 weeks
End stage renal disease at 96, 144 and 240 week	96, 144 and 240 weeks

Recruitment & Eligibility