Kidney Transplantation
Conditions
Brief summary
This three-arm study will evaluate the efficacy and safety of various dosing regimens of MMF combined with various dosing regimens of calcineurin inhibitor (CNI), either cyclosporine or tacrolimus, in participants who have undergone kidney transplantation. Participants will be randomized to one of three dosing regimens to receive concentration-controlled MMF with reduced CNI, concentration-controlled MMF with standard CNI, or fixed-dose MMF with standard CNI. Participants will be followed for 20-24 months after randomization.
Interventions
DRUGTacrolimus
Tacrolimus will be given as 1-mg and 5-mg capsules and dosed to maintain either reduced (Group A) or standard/full (Groups B and C) blood concentrations. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 4-6 ng/mL (reduced), 8-10 ng/mL (full); Days 90 through end of study, 3-5 ng/mL (reduced), 6-8 ng/mL (full).
DRUGMycophenolate mofetil
Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The initial dose will be at least 1 gram BID in adults and 600 mg/m\^2 in pediatrics. In Groups A and B, subsequent doses will be adjusted to maintain blood MPA levels ≥1.3 μg/mL with cyclosporine or ≥1.9 μg/mL with tacrolimus. In Group C, subsequent doses are not to be adjusted, except in the case of unacceptable toxicity.
DRUGCyclosporine
Cyclosporine will be given as 100-mg soft gelatin capsules and dosed to maintain either reduced (Group A) or standard/full (Groups B and C) blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 125-165 ng/mL (reduced) or 250-270 ng/mL (full); Days 90 through end of study, 95-145 ng/mL (reduced) or 190-220 ng/mL (full).
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Males or females 13-75 years of age * Single organ recipient (kidney only) from living (related or unrelated) or cadaveric heart-beating donors * Receiving first or second kidney transplant
Exclusion criteria
* Immunosuppressive therapy (except for 48 hours prior to transplantation and corticosteroid treatment) within previous 28 days for a first transplant and 3 months for a second transplant * History of malignancy in last 5 years (except successfully treated localized non-melanoma skin cancer)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants with Treatment Failure During 12 Months Post-Transplantation | Month 12 |
| Percent Change from Baseline in Calculated Glomerular Filtration Rate (GFR) at 12 Months Post-Transplantation | Baseline to Month 12 |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants by Number of BPAR Episodes | Months 6, 12, 20-24 |
| Percentage of Participants Treated for Acute Rejection (AR) | Months 6, 12, 20-24 |
| Percentage of Participants Who Experienced Graft Loss | Months 6, 12, 20-24 |
| Percentage of Participants Who Died | Months 6, 12, 20-24 |
| Percentage of Participants with Treatment Failure During 6 and 20-24 Months Post-Transplantation | Months 6, 20-24 |
| Time to First BPAR Episode | Months 6, 12, 20-24 |
| Time to Treatment Failure | Months 6, 12, 20-24 |
| Percent Change from Baseline in Calculated GFR at 3, 6, and 20-24 Months Post-Transplantation | Baseline to Months 3, 6, 20-24 |
| Percentage of Participants Who Discontinued Treatment with MMF | Months 6, 12, 20-24 |
| Percentage of Participants with Biopsy-Proven Acute Rejection (BPAR) | Months 6, 12, 20-24 |
Countries
United States
Outcome results
None listed