Back to resultsA Study of CellCept (Mycophenolate Mofetil) in Patients With Lupus Nephritis.
Primary Purpose
Lupus Nephritis
Status
Terminated
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Mycophenolate Mofetil
Corticosteroids
Azathioprine
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Nephritis
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Mycophenolate Mofetil
Cyclophosphamide/Azathioprine
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Complete Response
The median time, in months, to CR was defined as the time from randomization to CR event.
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.
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.
Percentage of Participants Terminating Treatment
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00425438
Brief Title
A Study of CellCept (Mycophenolate Mofetil) in Patients With Lupus Nephritis.
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Terminated
Why Stopped
Study was terminated early for administrative reasons.
Study Start Date
March 2007 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
April 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Nephritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mycophenolate Mofetil
Arm Type
Experimental
Arm Description
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.
Arm Title
Cyclophosphamide/Azathioprine
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
CellCept
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Corticosteroids
Other Intervention Name(s)
Prednisolone
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Azathioprine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
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
Primary Outcome Measure Information:
Title
Complete Response (CR) by the End of Treatment - Percentage of Participants With an Event
Description
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.
Time Frame
Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Secondary Outcome Measure Information:
Title
Complete Response
Description
The median time, in months, to CR was defined as the time from randomization to CR event.
Time Frame
Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Title
Percentage of Participants With Treatment Response Event by End of Treatment
Description
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.
Time Frame
Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Title
Percentage of Participants With a Decrease of 25% or 50% in Glomerular Filtration Rate (GFR)
Description
GFR was calculated according to the simplified modification of diet in renal disease (MDRD) formula.
Time Frame
Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Title
Percentage of Participants Terminating Treatment
Time Frame
Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Title
Time to Treatment Failure
Description
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.
Time Frame
Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Beijing
ZIP/Postal Code
100005
Country
China
City
Beijing
ZIP/Postal Code
100029
Country
China
City
Beijing
ZIP/Postal Code
100853
Country
China
City
Guangzhou
ZIP/Postal Code
510080
Country
China
City
Guangzhou
ZIP/Postal Code
510515
Country
China
City
Hangzhou
ZIP/Postal Code
310003
Country
China
City
Nanjing
ZIP/Postal Code
210008
Country
China
City
Shanghai
ZIP/Postal Code
200001
Country
China
City
Shanghai
ZIP/Postal Code
200003
Country
China
City
Shanghai
ZIP/Postal Code
200025
Country
China
City
Shenyang
ZIP/Postal Code
110001
Country
China
12. IPD Sharing Statement
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A Study of CellCept (Mycophenolate Mofetil) in Patients With Lupus Nephritis.
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