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

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: mycophenolate mofetil; Drug: tacrolimus, standard dose; Drug: corticosteroids; Drug: tacrolimus, low dose

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100020
  • Fuzhou, China, 350025
  • Guangzhou, China, 510080
  • Nanjing, China, 210008
  • Shanghai, China, 200025
  • Zhejiang, China, 310003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MMF, Standard Dose Tacrolimus; 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; 0.75-1 g PO BID from Day 0 through Month 12; Other Names: CellCept; Drug: tacrolimus, standard dose; 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.; Drug: corticosteroids; According to center's practice
Experimental: MMF, Low Dose Tacrolimus; 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; 0.75-1 g PO BID from Day 0 through Month 12; Other Names: CellCept; Drug: corticosteroids; According to center's practice; Drug: tacrolimus, low dose; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: September 24, 2008
• First Submitted That Met QC Criteria: September 24, 2008
• First Posted (Estimate): September 25, 2008

Study Record Updates

• Last Update Posted (Estimate): August 4, 2014
• Last Update Submitted That Met QC Criteria: July 8, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid
• Other Study ID Numbers: ML21740