A Study to Evaluate Efficacy of CellCept (Mycophenolate Mofetil) in Patients With Lupus Nephritis

Study Overview
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Brief Summary
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This study will compare the efficacy of CellCept [0.5-2 grams per day (g/day) orally (p.o.)] and cyclophosphamide [0.5-1 grams per square meter (g/m2) quarterly] as maintenance treatment for patients with lupus nephritis. All patients will receive induction treatment with cyclophosphamide (0.5-1g/m2 monthly) for 6 months, and will then be randomized to the maintenance phase of the study for a further 6 months, followed by 6 months of treatment-free follow-up. The anticipated time on study treatment is 12 months.

Official Title
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A Study to Evaluate the Efficacy of CellCept, Administered in a Sequential Treatment Scheme, in Delaying Progressive Renal Damage in Patients With Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Mycophenolate mofetil (MMF)
* Drug: Cyclophosphamide, Maintenance Phase
* Drug: Cyclophosphamide, Induction Phase
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients >=18 years of age; diagnosis of systemic lupus erythematosus and lupus nephritis (class III, IV or V). Exclusion Criteria: patients who have received cytotoxic drugs in previous 8 weeks; systemic infections; hepatitis B or C, or HIV.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: MMF, Prednisone<br>Induction Phase (Months 1 through 6): Participants received cyclophosphamide, 0.5 to (-) 1 grams per square meter (g/m^2), intravenously (IV) pulse once per month. Participants also received prednisone, 1 milligram per kilogram per day (mg/kg/day), orally (PO); the dose was reduced by 5 mg/day to a final dose of 10 mg/day. Maintenance Phase (Months 7 through 12): Participants received mycophenolate mofetil (MMF), 1 g/day, PO, twice daily (BID) for 2 weeks; 1.5 g/day, PO, three times daily (TID) for the next 2 weeks; 2 g/day, PO, BID for the remainder of the Maintenance Phase. Participants also received prednisone, as in the Induction Phase. | Drug: Mycophenolate mofetil (MMF)<br>* 1 g/day, PO BID for 2 weeks; 1.5 g/day PO TID for the next 2 weeks; and 2 g/day PO BID for the remainder of the Maintenance Phase.<br>* Other names: CellCept;Drug: Cyclophosphamide, Induction Phase<br>* 0.5 - 1 g/m^2 IV pulse once per month<br>Drug: Prednisone<br>* 1 mg/kg PO once per day; reduced by 5 mg every 2 weeks up to 20 mg/day; followed by a reduction of 2.5 mg every 2 weeks until reaching the maintenance phase of 10 mg/day.<br>|
| Active Comparator: Maintenance Cyclophosphamide, Prednisone<br>Induction Phase (Months 1 through 6): Participants received cyclophosphamide, 0.5 - 1 g/m^2, IV, pulse once per month. Participants also received prednisone, 1 mg/kg/day), PO; the dose was reduced by 5 mg/day to a final dose of 10 mg/day. Maintenance Phase (Months 7 through 12): Participants received cyclophosphamide, 0.5-1 g/m^2, IV, pulse once every 3 months. Participants also received prednisone, as in the Induction Phase. | Drug: Cyclophosphamide, Maintenance Phase<br>* 0.5-1 g/m^2 IV pulse once every 3 months<br>Drug: Cyclophosphamide, Induction Phase<br>* 0.5 - 1 g/m^2 IV pulse once per month<br>Drug: Prednisone<br>* 1 mg/kg PO once per day; reduced by 5 mg every 2 weeks up to 20 mg/day; followed by a reduction of 2.5 mg every 2 weeks until reaching the maintenance phase of 10 mg/day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Creatinine Clearance | Creatinine clearance in an indicator of kidney function. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult values are 97 to 137 milliliters per minute (mL/min) for males and 88 to 128 mL/min for females. | 18 months | 
| Urinary Protein | Protein in urine is an indicator of kidney function. An increased urinary protein level indicates decreased kidney function. Normal values are approximately 0 to 8 milligrams per deciliter (mg/dL). | 18 months | 
| Serum Creatinine | Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 mg/dL for females and 0.6 to 1.2 mg/dL for males, however the normal values are age-dependent as elderly participants typically have smaller muscle mass. | 18 months | 
| Serum Albumin | Albumin is a protein made by the liver. A serum albumin test measures the amount of this protein in the clear liquid portion of the blood. Decreased serum albumin levels can be an indicator of liver and/or kidney disease, The normal range is 3.4 - 5.4 grams (g)/dL. | 18 months |