A Study of CellCept (Mycophenolate Mofetil) in Patients With Lupus Nephritis.

Study Overview
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Brief Summary
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This 2 arm study will compare the efficacy and safety of CellCept plus corticosteroids, versus cyclophosphamide plus corticosteroids in the induction phase followed by azathioprine in the maintenance phase, in maintaining remission and renal function in patients with lupus nephritis. Patients will be randomized to receive CellCept 1g bid po plus corticosteroids for 24 weeks, followed by CellCept 0.75g bid po plus corticosteroids for the following 24 weeks, or cyclophosphamide 0.5-1.0g/m2 monthly plus corticosteroids for 24 weeks, followed by azathioprine 2mg/kg/day po plus corticosteroids for the following 24 weeks. Response rate will be assessed at the end of the induction phase, and at the end of study. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Official Title
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A Randomized, Open-label Study to Compare the Effect of CellCept Plus Corticosteroids, and Cyclophosphamide Plus Corticosteroids Followed by Azathioprine, on Remission Rate in Patients With Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Mycophenolate Mofetil
* Drug: Corticosteroids
* Drug: Azathioprine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-75 years of age; systemic lupus erythematosus; histological diagnosis of lupus nephritis. Exclusion Criteria: not in need of immunosuppressive treatment (in addition to corticosteroids); continuous dialysis starting >2 weeks before randomization, with an anticipated duration of >8 weeks; previous or planned kidney transplant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Mycophenolate Mofetil<br>Participants received mycophenolate mofetil (MMF) 0.5 grams (g), orally (PO), twice daily (BID) from Day 0 to the end of Week 1, followed by 1.0 g, PO, BID from Weeks 2 through 24, and 0.75 g, PO, BID from Weeks 32 to 48. Participants also received prednisolone 0.75 to 1.0 milligrams per kilogram (mg/kg), PO, once per day, up to a maximum of 60 mg per day from Weeks 1 through 4, reduced by 10 mg per day every 2 weeks until dose reaches 40 mg per day, followed by a reduction of 5 mg per day every 2 weeks until dose reaches 10 mg per day up to Week 48. | Drug: Mycophenolate Mofetil<br>* 0.5 g PO BID from Day 0 to the end of Week 1, followed by 1.0 g PO BID from Weeks 2 through 24, and 0.75 g PO BID from Weeks 32 to 48<br>* Other names: CellCept;Drug: Corticosteroids<br>* 0.75 to 1.0 mg/kg/d PO (up to 60 kg/day) from Weeks 1 through 4; reduced by 10 mg/day every 2 weeks until dose reaches 40 mg/day, followed by a reduction of 5 mg/day every 2 weeks until dose reaches 10 mg/day up to Week 48<br>* Other names: Prednisolone;|
| Active Comparator: Cyclophosphamide/Azathioprine<br>Participants received cyclophosphamide 0.75 grams per square meter (g/m^2), intravenously (IV), every 4 weeks from Weeks 1 through 4, and 0.5 to (-) 1.0 g/m^2, IV, to maintain a minimum white blood cell (WBC) count of greater than or equal to (≥) 2500 per cubic millimeter (mm^3) every 4 weeks from Weeks 5 through 24. Participants also received azathioprine 100 mg, PO, daily for participants with a body weight of 50 to 70 kg and 150 mg, PO, daily for subjects with a body weight of more than 70 kg from Weeks 25 through 48. Participants also received prednisolone 0.75 to 1.0 mg/kg, PO, once per day, up to a maximum of 60 mg per day from Weeks 1 through 4, reduced by 10 mg per day every 2 weeks until dose reaches 40 mg per day, followed by a reduction of 5 mg per day every 2 weeks until dose reaches 10 mg per day up to Week 48. | Drug: Corticosteroids<br>* 0.75 to 1.0 mg/kg/d PO (up to 60 kg/day) from Weeks 1 through 4; reduced by 10 mg/day every 2 weeks until dose reaches 40 mg/day, followed by a reduction of 5 mg/day every 2 weeks until dose reaches 10 mg/day up to Week 48<br>* Other names: Prednisolone;Drug: Azathioprine<br>* 100 mg PO daily for participants with a body weight of 50 to 70 kg,150 mg PO daily for subjects with a body weight of more than 70 kg up to Week 48<br>Drug: Cyclophosphamide<br>* 0.75 g/m^2 IV every 4 weeks from Weeks 1 through 4, and 0.5-1.0 g/m^2 to maintain a minimum WBC count of ≥ 2500 per mm^3 from Weeks 5 through 24<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) by the End of Treatment - Percentage of Participants With an Event | CR was defined as a urinary protein value of less than (<) 500 mg per 24 hours (mg/24h) and no hematuria or cellular casts in the urine, and a stable serum creatinine value within the range of plus or minus (±) 25 percent (%) of baseline (BL) or some improvement. | Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response | The median time, in months, to CR was defined as the time from randomization to CR event. | Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 | 
| Percentage of Participants With Treatment Response Event by End of Treatment | Treatment response was defined by a reduction in the ratio of urine protein to creatinine to <3 mg/mg for participants with nephrotic proteinuria and a decrease of more than 50% in their urine protein to creatinine value from BL for participants with non-nephrotic proteinuria; a stable serum creatinine value or an increase of more than 30% from BL; and having not received IV prednisone after Week 28. | Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 | 
| Percentage of Participants With a Decrease of 25% or 50% in Glomerular Filtration Rate (GFR) | GFR was calculated according to the simplified modification of diet in renal disease (MDRD) formula. | Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 | 
| Percentage of Participants Terminating Treatment |  | Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 | 
| Time to Treatment Failure | Treatment failure was defined as the occurrence of any of the following: death; chronic renal failure requiring dialysis or kidney transplantation; an increase in average serum creatinine values by 2-fold for 2 consecutive measures from BL, and a increase by 2-fold for 2 consecutive measures in at least 4 weeks; recurrent kidney disease defined by, proteinuria, a doubling in the ratio of urine protein to creatinine from BL and a urinary protein value of <0.5 g/24h or greater than (>) 1 g/24h or >0.5 g/24h or >2 g/24h at Week 24, kidney disease, defined by an increase in serum creatinine of 25% from BL along with a doubling of urinary protein of at least 2 g/24h, and hematuria, 2 or more blood cells per urine dipstick test. | Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 |