A Study of CellCept (Mycophenolate Mofetil) Combined With Tacrolimus and Corticosteroids in Kidney Transplant Patients.

Study Overview
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Brief Summary
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This 2 arm study will compare the efficacy and safety of CellCept, combined with low or standard dose tacrolimus plus corticosteroids, in patients with kidney transplants. Patients will be randomized into one of 2 groups to receive either 1)CellCept 2.0g/day po bid + tacrolimus 10-12ng/mL followed by a maintenance dose of 8-10ng/mL + corticosteroids or 2)CellCept 2.0g/day po bid + tacrolimus 8-10ng/mL in the first 2 months,3-7ng/mL in month 3 followed by a maintenance dose of 3-5ng/mL + corticosteroids. The anticipated time on study treatment is 1 year, and the target sample size is 100-500 individuals.

Official Title
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A Randomized, Open Label Study Comparing the Effect of CellCept Combined With Low Dose Versus Standard Dose Tacrolimus, and Corticosteroids, on Kidney Function in Renal Transplantation Patients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: mycophenolate mofetil
* Drug: tacrolimus, standard dose
* Drug: tacrolimus, low dose
* Drug: corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, <=75 years of age; single organ recipients of renal allograft; negative pregnancy test for women of childbearing potential; reliable contraception must be used before starting drug therapy, until 6 weeks after the last dose of study medication. Exclusion Criteria: severe gastrointestinal disease which may influence the absorption of oral drug therapy; severe infection, HIV or active hepatitis; active gastric ulcers; malignancy other than cured skin cancer; severe anemia, leucopenia or thrombocytopenia.

Ages Eligible for Study
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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 |
| --- | --- |
| Active Comparator: MMF, Standard Dose Tacrolimus<br>Participants received mycophenolate mofetil (MMF) 0.75 to (-) 1 gram (g), orally (PO), twice daily (BID) from Day 0 through Month 12. Participants also received tacrolimus 0.1-0.15 milligrams per kilogram (mg/kg), PO, BID to reach a target trough dose of 8-10 nanograms per milliliter (ng/mL) from Day 0 through Month 3; the dose was adjusted to reach a target trough level of 7-10 ng/mL in Month 3 and continued through Month 12. Participants also received corticosteroids per center practice. | Drug: mycophenolate mofetil<br>* 0.75-1 g PO BID from Day 0 through Month 12<br>* Other names: CellCept;Drug: tacrolimus, standard dose<br>* Initial dose of 0.1-0.15 mg/kg PO BID to reach a target trough dose of 8-10 ng/mL from Day 0 through Month 3; the dose was adjusted to reach a target trough level of 7-10 ng/mL in Month 3 and continued through Month 12.<br>Drug: corticosteroids<br>* According to center's practice<br>|
| Experimental: MMF, Low Dose Tacrolimus<br>Participants received MMF 0.75-1 g, PO, BID from Day 0 through Month 12. Participants also received tacrolimus 0.1-0.15 mg/kg, PO, BID to reach a target trough dose of 8-10 ng/mL from Day 0 through Month 3; the dose was adjusted to 0.05-0.08 mg/kg, PO, BID to reach a target trough dose of 2-5 ng/mL in Month 3 and continued through Month 12. Participants also received corticosteroids per center practice. | Drug: mycophenolate mofetil<br>* 0.75-1 g PO BID from Day 0 through Month 12<br>* Other names: CellCept;Drug: tacrolimus, low dose<br>* Initial dose of 0.1-0.15 mg/kg PO BID to reach a target trough dose of 8 to 10 ng/mL from Day 0 through Month 3; 0.05-0.08 mg/kg PO BID to reach a target trough dose of 2-5 ng/mL in Month 3 and continued through Month 12.<br>Drug: corticosteroids<br>* According to center's practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic Allograft Damage Index (CADI) Score at Month 12 After Transplantation | CADI scoring was defined for 6 histological categories: interstitial inflammatory cell infiltration (0 equals (=) no or mild inflammation, 1=approximately ( )25 percent (%) cell infiltration, 2=26-50% cell infiltration, and 3=greater than (>)50% cell infiltration); interstitial fibrosis (0=none, 1= 25% interstitial affected, 2=26-50% interstitial affected, and 3=>50% interstitial affected); tubular atrophy (0=none, 1= 15% proximal tubular atrophy [PTA], 2=16-30% PTA, and 3=>30% PTA); mesangial matrix proliferation (MMP; 0=none, 1=25% non-glomerulosclerosis [NGS] combined with moderate MMP, 2=25-50% NGS combined with MMP, and 3=>50% NGS combined with MMP); glomerular sclerosis (0=none, 1= 15% glomerulus affected, 2=16-50% glomerulus affected, and 3=>50% glomerulus affected); endothelial proliferation (EP; 0=none, 1=EP to less than (<)25% remaining artery/small artery membrane [RA/SAM], 2=EP to 26-50% [RA/SAM], and 3=>50% [RA/SAM]). CADI score was the sum of the 6 histological findings. | Month 12 | 
| Glomerular Filtration Rate (GFR) at Month 12 After Transplantation | GFR was determined using the Cockcroft-Gault formula to calculate the creatinine clearance, at Month 12 after renal transplantation. For males, creatinine clearance [milliliters per minute (mL/min)] = [(140 minus age) multiplied by (*) (body weight in kg) divided by [72 * serum creatinine mg per deciliter (mg/dL)]. For females, creatinine clearance (mL/min) = 0.85 * [(140 minus age) * (body weight in kg)] divided by [72 * serum creatinine (mg/dL)]. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Acute Rejection, Graft Loss, or Death at 6 and 12 Months Post-Transplant |  | Months 6 and 12 | 
| Time to First Acute Rejection Post-Transplant - Number of Participants With an Event |  | BL, Weeks 2, 4, 13, 26, 39, and 52 | 
| Time to First Acute Rejection Post-Transplant | The median time, in days, between randomization and acute rejection. | BL, Weeks 2, 4, 13, 26, 39, and 52 | 
| Percentage of Participants With Treatment Failure at 12 Months Post-Transplant | Treatment failure was defined by the occurrence of any of the following: use of additional maintenance immunosuppressive medication not specified in the assigned treatment group; discontinuation of any of the assigned immunosuppressants for more than 14 consecutive days or 30 cumulative days; graft loss or return to chronic dialysis; or death. | Month 12 | 
| Participant and Graft Survival | The percentage of participants surviving with grafts intact at 6 and 12 months after renal transplant. | Months 6 and 12 | 
| Serum Creatinine (Micromoles Per Liter [µmol/L]) | The mean serum creatinine values in µmol/L at Baseline (BL), Weeks 2, 4, 13, 26, 39, and 52. | BL, Weeks 2, 4, 13, 26, 39, and 52 | 
| Glomerular Filtration Rate (GFR) (mL/Min) | The mean GFR values in mL/min at BL, Weeks 2, 4, 13, 26, 39, and 52. | BL, Weeks 2, 4, 13, 26, 39, and 52 |