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

Study Overview
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Brief Summary
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A randomized open-label study of fixed-dose versus concentration-controlled mycophenolate mofetil for treatment of active lupus nephritis.

Official Title
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A Randomized Open-label Study of Fixed-dose Versus Concentration-controlled Mycophenolate Mofetil for the Treatment of Active Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Mycophenolate Mofetil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: FD arm<br>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. | Drug: Mycophenolate Mofetil<br>* Description Each capsule contains Mycophenolate mofetil 250 mg. Presentation / Packing Cap 250 mg (white to off white powder, light blue/peach hard gelatin, imprinting with MMF on cap and 250 on body) x 10 x 10's. Storage Store below 30 degree Celcius.<br>|
| Active Comparator: CC Arm<br>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 | Drug: Mycophenolate Mofetil<br>* Description Each capsule contains Mycophenolate mofetil 250 mg. Presentation / Packing Cap 250 mg (white to off white powder, light blue/peach hard gelatin, imprinting with MMF on cap and 250 on body) x 10 x 10's. Storage Store below 30 degree Celcius.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate at 48 week of therapy |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | 48 weeks | 
| Mycophenolic acid trough levels |  | 48 weeks | 
| MPA-area under the curve (AUC) 0-4 hour at 12 week |  | 12 weeks | 
| C3 levels |  | 48 weeks | 
| Urine IP-10 levels |  | 48 weeks | 
| Anti-dsDNA |  | 48 weeks | 
| Relapse free survival at 96, 144 and 240 week |  | 96, 144 and 240 weeks | 
| eGFR at 96, 144 and 240 week |  | 96, 144 and 240 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 |