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

Phase 4

Completed

• Conditions: Kidney Transplantation
• Interventions: Drug: mycophenolate mofetil; Drug: tacrolimus, low dose; Drug: tacrolimus, standard dose; Drug: corticosteroids

• Registration Number: NCT00758602
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09
• Study First Submitted: 2008-09-24
• Study First Submitted QC: 2008-09-24
• Study First Posted: 2008-09-25
• Primary Completion: 2011-02
• Study Completion: 2011-02
• Status Verified: 2014-07
• Results First Submitted: 2014-07-08
• Results First Submitted QC: 2014-07-08
• Last Update Submitted: 2014-07-08
• Results First Posted: 2014-08-04
• Last Update Posted: 2014-08-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 210

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MMF, Standard Dose Tacrolimus	corticosteroids	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.
MMF, Low Dose Tacrolimus	corticosteroids	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.
MMF, Low Dose Tacrolimus	mycophenolate mofetil	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.
MMF, Low Dose Tacrolimus	tacrolimus, low dose	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.
MMF, Standard Dose Tacrolimus	tacrolimus, standard dose	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.
MMF, Standard Dose Tacrolimus	mycophenolate mofetil	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.

Primary Outcome Measures

Name	Time	Method
Glomerular Filtration Rate (GFR) at Month 12 After Transplantation	Month 12	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 \[72 \* serum creatinine (mg/dL)\].
Chronic Allograft Damage Index (CADI) Score at Month 12 After Transplantation	Month 12	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.

Secondary Outcome Measures

Name	Time	Method
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
Participant and Graft Survival	Months 6 and 12	The percentage of participants surviving with grafts intact at 6 and 12 months after renal transplant.
Serum Creatinine (Micromoles Per Liter [µmol/L])	BL, Weeks 2, 4, 13, 26, 39, and 52	The mean serum creatinine values in µmol/L at Baseline (BL), Weeks 2, 4, 13, 26, 39, and 52.
Time to First Acute Rejection Post-Transplant	BL, Weeks 2, 4, 13, 26, 39, and 52	The median time, in days, between randomization and acute rejection.
Glomerular Filtration Rate (GFR) (mL/Min)	BL, Weeks 2, 4, 13, 26, 39, and 52	The mean GFR values in mL/min at BL, Weeks 2, 4, 13, 26, 39, and 52.
Percentage of Participants With Treatment Failure at 12 Months Post-Transplant	Month 12	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.