Lupus Nephritis
Conditions
Brief summary
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.
Interventions
DRUGMycophenolate mofetil (MMF)
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.
DRUGCyclophosphamide, Maintenance Phase
0.5-1 g/m\^2 IV pulse once every 3 months
DRUGCyclophosphamide, Induction Phase
0.5 - 1 g/m\^2 IV pulse once per month
DRUGPrednisone
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Creatinine Clearance | 18 months | 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. |
| Urinary Protein | 18 months | 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). |
| Serum Creatinine | 18 months | 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. |
| Serum Albumin | 18 months | 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. |
Countries
Venezuela
Participant flow
Recruitment details
Protocol Approved by National Regulatory Agency on 25 October 2005 and inclusion period ended on 21 January 2008, on three investigational sites but only two sites included patients. Sites were selected in public health care systems.
Pre-assignment details
Screening period include only the assessments to verified the inclusion and exclusion criteria's from ICF signature until base line visit (first dose day), no washout or run in period was expected.
Participants by arm
| Arm | Count |
|---|---|
| MMF, Prednisone Induction Phase (Months 1 through 6): Participants received cyclophosphamide, 0.5 -1 g/m\^2, IV once per month. Participants also received prednisone, 1 mg/kg/day, tablets (or methylprednisolone IV), PO; the dose was reduced by 5 mg every 2 weeks up to 20 mg/day, then reduced by 2.5 mg every 2 weeks to a final maintenance dose of 10 mg/day.
Maintenance Phase (Months 7 through 12): Participants received MMF, 500 mg, tablets or capsules, PO, twice daily (BID) for 2 weeks; 500 mg, PO, three times daily (TID) for the next 2 weeks; 1 g, PO, BID for the remainder of the Maintenance Phase. Participants continued to receive maintenance prednisone (10 mg/day), as in the Induction Phase. | 5 |
| Cyclophosphamide, Prednisone Induction Phase (Months 1 through 6): Participants received cyclophosphamide, 0.5 -1 g/m\^2, IV once per month. Participants also received prednisone, 1 mg/kg/day, tablets (or methylprednisolone IV) PO; the dose was reduced by 5 mg every 2 weeks up to 20 mg/day, then reduced by 2.5 mg every 2 weeks to a final maintenance dose of 10 mg/day.
Maintenance Phase (Months 7 through 12): Participants received cyclophosphamide, 0.5-1 g/m\^2, IV, once every 3 months. Participants continued to receive maintenance prednisone (10 mg/day), as in the Induction Phase. | 6 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 3 | 3 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | MMF, Prednisone | Cyclophosphamide, Prednisone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Region of Enrollment Venezuela | 5 participants | 6 participants | 11 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 2 / 6 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 |
Outcome results
Primary
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.
Time frame: 18 months
Population: Data were not analyzed because the study was terminated early.
Primary
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.
Time frame: 18 months
Population: Data were not analyzed because the study was terminated early.
Primary
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.
Time frame: 18 months
Population: Data were not analyzed because the study was terminated early.
Primary
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).
Time frame: 18 months
Population: Data were not analyzed because the study was terminated early.