A Study of CellCept (Mycophenolate Mofetil) in Patients With Lupus Nephritis.
- Conditions
- Lupus Nephritis
- Interventions
- Registration Number
- NCT00425438
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 52
- adult patients, 18-75 years of age;
- systemic lupus erythematosus;
- histological diagnosis of lupus nephritis.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mycophenolate Mofetil Corticosteroids 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. Cyclophosphamide/Azathioprine Corticosteroids 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. Mycophenolate Mofetil Mycophenolate Mofetil 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. Cyclophosphamide/Azathioprine Azathioprine 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. Cyclophosphamide/Azathioprine Cyclophosphamide 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.
- Primary Outcome Measures
Name Time Method Complete Response (CR) by the End of Treatment - Percentage of Participants With an Event Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Treatment Response Event by End of Treatment Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 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.
Complete Response Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 The median time, in months, to CR was defined as the time from randomization to CR event.
Percentage of Participants With a Decrease of 25% or 50% in Glomerular Filtration Rate (GFR) Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 GFR was calculated according to the simplified modification of diet in renal disease (MDRD) formula.
Percentage of Participants Terminating Treatment Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 Time to Treatment Failure Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 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.