Study of Therapeutic Monitoring of Mycophenolate Mofetil (MMF/CellCept) After Kidney Transplantation

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Study arms

• Experimental
  Group A: Monitored MMF + Reduced CNI

  Group A will receive concentration-controlled/monitored MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or intravenous (IV) form. The initial dose will be at least 1 gram twice a day (BID) in adults and 600 milligrams per meter-squared (mg/m\^2) in pediatrics. Subsequent doses will be adjusted to maintain blood mycophenolic acid (MPA) levels greater than or equal to (≥) 1.3 micrograms per milliliter (μg/mL) with cyclosporine or ≥1.9 μg/mL with tacrolimus. The selected CNI will be dosed to maintain reduced blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 nanograms per milliliter (ng/mL); Days 30-90, 125-165 ng/mL; Days 90 through end of study, 95-145 ng/mL. Tacrolimus target concentrations areas follows: Days 1-30, 8-12 ng/mL; Days 30-90, 4-6 ng/mL; Days 90 through end of study, 3-5 ng/mL.

  Drug: Mycophenolate mofetil · Drug: Cyclosporine · Drug: Tacrolimus

• Experimental
  Group B: Monitored MMF + Full CNI

  Group B will receive concentration-controlled/monitored MMF with an oral CNI, either cyclosporine or tacrolimus. 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. Subsequent doses will be adjusted to maintain blood MPA levels ≥1.3 μg/mL with cyclosporine or ≥1.9 μg/mL with tacrolimus. The selected CNI will be dosed to maintain standard/full blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 250-270 ng/mL; Days 90 through end of study, 190-220 ng/mL. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 8-10 ng/mL; Days 90 through end of study, 6-8 ng/mL.

  Drug: Mycophenolate mofetil · Drug: Cyclosporine · Drug: Tacrolimus

• Experimental
  Group C: Fixed MMF + Full CNI

  Group C will receive fixed-dose MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The dose will be at least 1 gram BID in adults and 600 mg/m\^2 in pediatrics. Subsequent doses are not to be adjusted, except in the case of unacceptable toxicity. The selected CNI will be dosed to maintain standard/full blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 250-270 ng/mL; Days 90 through end of study, 190-220 ng/mL. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 8-10 ng/mL; Days 90 through end of study, 6-8 ng/mL.

  Drug: Mycophenolate mofetil · Drug: Cyclosporine · Drug: Tacrolimus

Interventions

• 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.

  Also known as: CellCept

• 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).

  Also known as: Neoral

• 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).

  Also known as: Prograf

Primary outcomes

1. Percentage of Participants with Treatment Failure During 12 Months Post-Transplantation

   Time frame: Month 12

2. Percent Change from Baseline in Calculated Glomerular Filtration Rate (GFR) at 12 Months Post-Transplantation

   Time frame: Baseline to Month 12

Secondary outcomes

1. Percentage of Participants with Treatment Failure During 6 and 20-24 Months Post-Transplantation

   Time frame: Months 6, 20-24

2. Percentage of Participants with Biopsy-Proven Acute Rejection (BPAR)

   Time frame: Months 6, 12, 20-24

3. Percentage of Participants by Number of BPAR Episodes

   Time frame: Months 6, 12, 20-24

4. Percentage of Participants Treated for Acute Rejection (AR)

   Time frame: Months 6, 12, 20-24

5. Percentage of Participants Who Experienced Graft Loss

   Time frame: Months 6, 12, 20-24

6. Percentage of Participants Who Died

   Time frame: Months 6, 12, 20-24

7. Percentage of Participants Who Discontinued Treatment with MMF

   Time frame: Months 6, 12, 20-24

8. Time to First BPAR Episode

   Time frame: Months 6, 12, 20-24

9. Time to Treatment Failure

   Time frame: Months 6, 12, 20-24

10. Percent Change from Baseline in Calculated GFR at 3, 6, and 20-24 Months Post-Transplantation

    Time frame: Baseline to Months 3, 6, 20-24