Lupus Nephritis
Conditions
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.
Interventions
DRUGMycophenolate Mofetil
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
DRUGCorticosteroids
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
DRUGAzathioprine
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
DRUGCyclophosphamide
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
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 up to 48 weeks after Week 24. 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 reached 40 mg/day, followed by a reduction of 5 mg/day every 2 weeks until dose reached 10 mg per day up to Week 48. | 25 |
| Cyclophosphamide, Azathioprine Participants received cyclophosphamide 0.75 g/m\^2, IV, every 4 weeks from Weeks 1 through 4, and 0.5-1.0 g/m\^2, IV, to maintain a minimum WBC count of 2500/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 participants 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 reached 40 mg/day, followed by a reduction of 5 mg/day every 2 weeks until dose reached 10 mg per day up to Week 48. | 27 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Termination by Sponsor | 25 | 27 |
Baseline characteristics
| Characteristic | Mycophenolate Mofetil | Cyclophosphamide, Azathioprine | Total |
|---|---|---|---|
| Age, Continuous | 33.4 years STANDARD_DEVIATION 9.8 | 31.6 years STANDARD_DEVIATION 8 | 32.4 years STANDARD_DEVIATION 8.9 |
| Sex: Female, Male Female | 22 Participants | 23 Participants | 45 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 25 | 18 / 27 |
| serious Total, serious adverse events | 8 / 25 | 5 / 27 |
Outcome results
Primary
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.
Time frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Population: Efficacy data were not analyzed because of study termination. The study was terminated early for administrative reasons and no participants completed all planned study visits; therefore efficacy analyses could not be performed.
Secondary
Complete Response
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
Population: Efficacy data were not analyzed because of study termination. The study was terminated early for administrative reasons and no participants completed all planned study visits; therefore efficacy analyses could not be performed.
Secondary
Percentage of Participants Terminating Treatment
Time frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Population: Efficacy data were not analyzed because of study termination. The study was terminated early for administrative reasons and no participants completed all planned study visits; therefore efficacy analyses could not be performed.
Secondary
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.
Time frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Population: Efficacy data were not analyzed because of study termination. The study was terminated early for administrative reasons and no participants completed all planned study visits; therefore efficacy analyses could not be performed.
Secondary
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.
Time frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Population: Efficacy data were not analyzed because of study termination. The study was terminated early for administrative reasons and no participants completed all planned study visits; therefore efficacy analyses could not be performed.
Secondary
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.
Time frame: Screening, Day 0, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Population: Efficacy data were not analyzed because of study termination. The study was terminated early for administrative reasons and no participants completed all planned study visits; therefore efficacy analyses could not be performed.