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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A: Monitored MMF + Reduced CNI | Experimental | 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. |
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| Group B: Monitored MMF + Full CNI | Experimental | 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. |
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| Group C: Fixed MMF + Full CNI |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mycophenolate mofetil | Drug | 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. |
| Measure | Description | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Treatment Failure During 6 and 20-24 Months Post-Transplantation | Months 6, 20-24 | |
| Percentage of Participants with Biopsy-Proven Acute Rejection (BPAR) | Months 6, 12, 20-24 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham | Alabama | 35294 | United States | |||
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| Experimental |
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. |
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| Cyclosporine | Drug | 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). |
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| Tacrolimus | Drug | 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). |
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| 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 Who Discontinued Treatment with MMF | Months 6, 12, 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 |
| Little Rock |
| Arkansas |
| 72205 |
| United States |
| Bakersfield | California | 93309 | United States |
| Los Angeles | California | 90048 | United States |
| Los Angeles | California | 90057 | United States |
| San Francisco | California | 94143-0116 | United States |
| Denver | Colorado | 80262 | United States |
| Gainesville | Florida | 32610-0224 | United States |
| Jacksonville | Florida | 32216 | United States |
| Miami | Florida | 33101 | United States |
| Orlando | Florida | 32804 | United States |
| Tampa | Florida | 33606 | United States |
| Augusta | Georgia | 30912 | United States |
| Chicago | Illinois | 60637 | United States |
| Indianapolis | Indiana | 46202-5124 | United States |
| Wichita | Kansas | 67214 | United States |
| Lexington | Kentucky | 40536-0293 | United States |
| New Orleans | Louisiana | 70121 | United States |
| Shreveport | Louisiana | 71130 | United States |
| Baltimore | Maryland | 21287-8611 | United States |
| Boston | Massachusetts | 02111 | United States |
| Boston | Massachusetts | 02215 | United States |
| Burlington | Massachusetts | 01805 | United States |
| Springfield | Massachusetts | 01107 | United States |
| Worcester | Massachusetts | 01655 | United States |
| Ann Arbor | Michigan | 48109-0362 | United States |
| Detroit | Michigan | 48202-2689 | United States |
| Rochester | Minnesota | 55905 | United States |
| Hackensack | New Jersey | 07601 | United States |
| Livingston | New Jersey | 07039 | United States |
| Buffalo | New York | 14203 | United States |
| Hawthorne | New York | 10532 | United States |
| New York | New York | 10021 | United States |
| New York | New York | 10029 | United States |
| New York | New York | 10032 | United States |
| Rochester | New York | 14642-8410 | United States |
| The Bronx | New York | 10467 | United States |
| Chapel Hill | North Carolina | 27599 | United States |
| Winston-Salem | North Carolina | 27157 | United States |
| Fargo | North Dakota | 58122 | United States |
| Cleveland | Ohio | 44106 | United States |
| Portland | Oregon | 97210 | United States |
| Harrisburg | Pennsylvania | 17101 | United States |
| Hershey | Pennsylvania | 17033 | United States |
| Philadelphia | Pennsylvania | 19102-1192 | United States |
| Philadelphia | Pennsylvania | 19104 | United States |
| Philadelphia | Pennsylvania | 19140 | United States |
| Pittsburgh | Pennsylvania | 15212 | United States |
| Providence | Rhode Island | 02903 | United States |
| Dallas | Texas | 75246 | United States |
| San Antonio | Texas | 78284 | United States |
| Salt Lake City | Utah | 84132 | United States |
| Burlington | Vermont | 05401 | United States |
| Falls Church | Virginia | 22042-3300 | United States |
| Norfolk | Virginia | 23502 | United States |
| Seattle | Washington | 98104 | United States |
| Madison | Wisconsin | 53792 | United States |
| ID | Term |
|---|---|
| D009173 | Mycophenolic Acid |
| D016572 | Cyclosporine |
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D018942 | Macrolides |
| D007783 | Lactones |
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