Regimen Optimization Study
- Conditions
- Kidney Transplantation
- Interventions
- Drug: CorticosteroidsDrug: Everolimus(EVL)Drug: Tacrolimus(TAC)
- Registration Number
- NCT02137239
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Patients who undergo a kidney transplant require prolonged therapy with drugs that suppress the immune system (called immunosuppressive regimens) to stop the immune system from attacking the transplanted kidney in order to limit damage to or the possibility of rejecting the transplanted kidney. The purpose of this study is to evaluate benefits and risks of two immunosuppressive regimens (belatacept with everolimus or tacrolimus with mycophenolate mofetil) following thymoglobulin induction and rapid corticosteroid withdrawal.
- Detailed Description
Calcineurin inhibitor (CNI)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 58
- Men and women, aged 18 to 75
- Serologic test results are positive for past exposure to Epstein Barr Virus (EBV+)
- Diagnosed with end stage renal disease (ESRD) and scheduled to undergo transplantation of a non-HLA identical, living or standard criteria deceased donor kidney
- Primary cause of ESRD is: primary focal segmental glomerulosclerosis; or Type I or II membranoproliferative glomerulonephritis; or Hemolytic Uremic Syndrome / Thrombotic Thrombocytopenic Purpura
- Had a previous graft loss due to acute rejection
- At increased immunologic risk of graft loss due to panel reactive antibodies (PRA) >20% or need for desensitization therapy
- Scheduled to receive a: kidney from identical twin; or paired kidney; or kidney from a Cytomegalovirus(CMV) positive donor when recipient is CMV negative; or kidney from an extended criteria donor
- Have a body mass index (BMI) of > 35 kg/m2 for nondiabetics or > 30 kg/m2 for diabetics
- Diagnosed as Hepatitis B positive; or Hepatitis C positive; or HIV positive; or currently or previously active or inadequately treated latent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Belatacept + Everolimus Corticosteroids Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; belatacept (infusion) regimen of 10 mg/kg i.v. on Day 1, Weeks 1, 2, 4, 8 and 12 post transplant and then a maintenance dose of 5 mg/kg every 4 weeks after 12 weeks post transplant; everolimus (tablet) daily dosing at 3.0 mg/day, 2 divided doses, starting on Day 3 dosing adjusted based on blood sample tests; methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed) Belatacept + Everolimus Everolimus(EVL) Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; belatacept (infusion) regimen of 10 mg/kg i.v. on Day 1, Weeks 1, 2, 4, 8 and 12 post transplant and then a maintenance dose of 5 mg/kg every 4 weeks after 12 weeks post transplant; everolimus (tablet) daily dosing at 3.0 mg/day, 2 divided doses, starting on Day 3 dosing adjusted based on blood sample tests; methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed) Tacrolimus + Mycophenolate mofetil mycophenolate mofetil(MMF) Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; tacrolimus (tablet) daily dosing beginning at 0.1 mg/kg/day, then adjusted based on blood sample tests; MMF (tablet) daily dosing between 0.5 to 2.0 g/day divided in 2 doses (up to 3 g/day if African Americans/Blacks); methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed) Tacrolimus + Mycophenolate mofetil Corticosteroids Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; tacrolimus (tablet) daily dosing beginning at 0.1 mg/kg/day, then adjusted based on blood sample tests; MMF (tablet) daily dosing between 0.5 to 2.0 g/day divided in 2 doses (up to 3 g/day if African Americans/Blacks); methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed) Tacrolimus + Mycophenolate mofetil Tacrolimus(TAC) Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; tacrolimus (tablet) daily dosing beginning at 0.1 mg/kg/day, then adjusted based on blood sample tests; MMF (tablet) daily dosing between 0.5 to 2.0 g/day divided in 2 doses (up to 3 g/day if African Americans/Blacks); methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed) Belatacept + Everolimus Thymoglobulin Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; belatacept (infusion) regimen of 10 mg/kg i.v. on Day 1, Weeks 1, 2, 4, 8 and 12 post transplant and then a maintenance dose of 5 mg/kg every 4 weeks after 12 weeks post transplant; everolimus (tablet) daily dosing at 3.0 mg/day, 2 divided doses, starting on Day 3 dosing adjusted based on blood sample tests; methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed) Tacrolimus + Mycophenolate mofetil Thymoglobulin Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; tacrolimus (tablet) daily dosing beginning at 0.1 mg/kg/day, then adjusted based on blood sample tests; MMF (tablet) daily dosing between 0.5 to 2.0 g/day divided in 2 doses (up to 3 g/day if African Americans/Blacks); methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed) Belatacept + Everolimus Belatacept Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; belatacept (infusion) regimen of 10 mg/kg i.v. on Day 1, Weeks 1, 2, 4, 8 and 12 post transplant and then a maintenance dose of 5 mg/kg every 4 weeks after 12 weeks post transplant; everolimus (tablet) daily dosing at 3.0 mg/day, 2 divided doses, starting on Day 3 dosing adjusted based on blood sample tests; methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed)
- Primary Outcome Measures
Name Time Method Percentage of Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6 Months 6 Months Number of Participants with Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6 Months
- Secondary Outcome Measures
Name Time Method Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6, 12 and 24 Months Up to 24 Months Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6, 12 and 24 Months
Change in the incidence of CSBPAR at 6, 12 and 24 months post transplant, in the belatacept + EVL(Treatment A) as compared to TAC + MMF (Treatment B).Time to Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR). Up to 24 Months Time to Clinically suspected biopsy proven acute rejection
Percentage of Participants With BANFF Grade by Severity Grades. BANFF Type (Grade) for Acute/Active Rejection At 6, 12 and 24 Months Treatment differences in the severity grades to treat all episodes of CSBPAR at 6, 12, and 24 months post-transplant.
Type 1A - Cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>4 mononuclear cells/Tubular cross section or group of 10 Tubular cell). Type 1B - Cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>10 mononuclear cells/Tubular cross section or group of 10 Tubular cell).Type 2A - Cases with mild to moderate intimal arteritis.Type 2B - Cases with severe intimal arteritis comprising \>25% of the luminal area. Type 3 - Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (v3 with accompanying lymphocytic inflammation)Treatment Differences in Therapeutic Modalities at 6, 12 and 24 Months Treatment Received for Biopsy Proven Acute Rejection (Banff Grade IA or Higher), or Humoral (Antibody Mediated) Rejection Treatment regimen: Categorical analysis of CSBPAR episodes by treatment received.
Number of Participants Who Survive With a Functioning Graft At 6, 12 and 24 months Number of all participants who survive with a functioning graft at 6, 12 and 24 months post transplant
Number of Participants Deaths Post Transplant up to 24 months Number of participant deaths at 6, 12 and 24 months post transplant
Number of Participants Who Experience Graft Loss Post Transplant At 6, 12 and 24 months Number of all participants who experience graft loss at 6, 12 and 24 months post transplant
Time to Event: Graft Loss and Death Up to 728 Days The Number of days to participant Graft Loss and death for any reason
Absolute Calculated Glomerular Filtration Rate (cGFR): Mean Up 24 Months post-transplant Absolute (mean and median) cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula
Median Calculated Glomerular Filtration Rate (cGFR) Up 24 Months post-transplant Median cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula
Mean Change From Month 3 in cGFR Up 24 Months post-transplant The mean change from Month 3 cGFR at 3, 6, 12 and 24 months post-transplant
Urine Protein Creatinine Ratio (UPr/Cr) Up 24 Months post-transplant Urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.
Percentage of Participants With Donor Specific Anti-HLA Antibodies (DSA) Up to 24 Months Percentage of participants with, and titers of pre-existing (pre-transplant) DSA on Day 1 (pre-transplant, pre-dose), and at Months 12 and 24 posttransplant
Percentage of Participants With De Novo Donor Specific Anti-HLA Antibodies (DSA) Up to 24 Months Characterization of any de novo DSA detected by IgM and IgG subclasses, and by the presence or absence of complement fixing properties.
Percentage of Participants With Adverse Events (AEs) Up to 24 months Post-Transplant Percentage of participants with AEs up to 24 months post-transplant
Percentage of Participants With Serious Adverse Events (SAEs) Up to 24 months Post-Transplant Percentage of participants with SAEs up to 24 months post-transplant
Percentage of Participants With Events of Special Interest (ESIs) Up to 24 Months Percentage of participants which have one of the following events of special interest:
Serious Infections Post-Transplant Lymphoproliferative Disorder (PTLD) Progressive multifocal leukoencephalopathy (PML) Malignancies (Other than PTLD) including non-melanoma skin carcinomas (Malignancies) Tuberculosis Infections Central Nervous System (CNS) Infections Viral Infections Infusion Related reactions within 24 hours since belatacept infusionPercentage of Particpants With Laboratory Test Abnormalities (LTAs) At 24 Months Percentage of participants with laboratory tests with marked laboratory abnormalities
Mean and Mean Change From Baseline in Blood Glucose Up to 24 months Mean fasting blood glucose levels, and mean changes from baseline values at Months 6, 12 and 24 months post- transplant
Mean and Mean Change From Baseline in Whole Blood HbA1c Up to 24 months Mean whole blood HbA1C concentrations, and mean changes from baseline values at Months 6, 12 and 24 months post-transplant.
Percentage of Participants With New Onset Diabetes After Transplant up to 24 months Percentage of participants with New Onset Diabetes After Transplantation (NODAT) at 6, 12, and 24 months post-transplant.
Absolute Values of Blood Pressure: Mean Up to 24 Months Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;
Absolute Values of Blood Pressure: Median Up to 24 Months Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;
Mean Changes From Baseline Values for Blood Pressure Up to 24 Months Mean changes from baseline values for SBP and DBP at 6, 12 and 24 months post-transplant
Absolute Values of Fasting Lipid Values: Mean Up to 24 Months Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant for the following:
Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)Absolute Values of Fasting Lipid Values: Median Up to 24 Months Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant for the following:
Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)Mean Changes From Baseline Values of Lipid Values at months 12 and 24 Mean changes from baseline values in the following:
Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)
Trial Locations
- Locations (20)
Emory Univeristy
🇺🇸Atlanta, Georgia, United States
University Of Illinois
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Swedish Medical Center - Swedish Colon and Rectal Clinic - First Hill (Northwest Colon and Rectal Cl
🇺🇸Seattle, Washington, United States
California Institute Of Renal Research
🇺🇸San Diego, California, United States
Sanatorio Parque S.A.
🇦🇷Rosario, Santa Fe, Argentina
Central PA Transplant Foundation
🇺🇸Harrisburg, Pennsylvania, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Tulane Medical Center
🇺🇸New Orleans, Louisiana, United States
Clinica De Nefrologia, Urologia Y Enf. Cardiovasculares
🇦🇷Sante Fe, Argentina
California Pacific Medical Center
🇺🇸San Francisco, California, United States
University Of Colorado
🇺🇸Aurora, Colorado, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Yale University
🇺🇸New Haven, Connecticut, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Wake Forest University School Of Medicine
🇺🇸Winston-Salem, North Carolina, United States
Erie County Medical Center
🇺🇸Buffalo, New York, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Clinica Privada Velez Sarsfield
🇦🇷Cordoba, Argentina
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States