Evaluation of Acute Rejection Rates in de Novo Renal Transplant Recipients Following Thymoglobulin Induction, CNI-free, Nulojix (Belatacept)-Based Immunosuppression
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 58
- 试验地点
- 20
- 主要终点
- Percentage of Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6 Months
研究概览
简要总结
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.
详细描述
Calcineurin inhibitor (CNI)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Belatacept + Everolimus
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)
干预措施: Thymoglobulin (Drug)
Belatacept + Everolimus
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)
干预措施: Belatacept (Drug)
Belatacept + Everolimus
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)
干预措施: Corticosteroids (Drug)
Belatacept + Everolimus
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)
干预措施: Everolimus(EVL) (Drug)
Tacrolimus + Mycophenolate mofetil
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)
干预措施: Thymoglobulin (Drug)
Tacrolimus + Mycophenolate mofetil
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)
干预措施: mycophenolate mofetil(MMF) (Drug)
Tacrolimus + Mycophenolate mofetil
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)
干预措施: Corticosteroids (Drug)
Tacrolimus + Mycophenolate mofetil
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)
干预措施: Tacrolimus(TAC) (Drug)
结局指标
主要结局
Percentage of Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6 Months
时间窗: 6 Months
Number of Participants with Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6 Months
次要结局
- Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6, 12 and 24 Months(Up to 24 Months)
- Time to Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR).(Up to 24 Months)
- 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 Therapeutic Modalities(at 6, 12 and 24 Months)
- Number of Participants Who Survive With a Functioning Graft(At 6, 12 and 24 months)
- Number of Participants Deaths Post Transplant(up to 24 months)
- Number of Participants Who Experience Graft Loss Post Transplant(At 6, 12 and 24 months)
- Time to Event: Graft Loss and Death(Up to 728 Days)
- Absolute Calculated Glomerular Filtration Rate (cGFR): Mean(Up 24 Months post-transplant)
- Median Calculated Glomerular Filtration Rate (cGFR)(Up 24 Months post-transplant)
- Mean Change From Month 3 in cGFR(Up 24 Months post-transplant)
- Urine Protein Creatinine Ratio (UPr/Cr)(Up 24 Months post-transplant)
- Percentage of Participants With Donor Specific Anti-HLA Antibodies (DSA)(Up to 24 Months)
- Percentage of Participants With De Novo Donor Specific Anti-HLA Antibodies (DSA)(Up to 24 Months)
- Percentage of Participants With Adverse Events (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 Events of Special Interest (ESIs)(Up to 24 Months)
- Percentage of Particpants With Laboratory Test Abnormalities (LTAs)(At 24 Months)
- Mean and Mean Change From Baseline in Blood Glucose(Up to 24 months)
- Mean and Mean Change From Baseline in Whole Blood HbA1c(Up to 24 months)
- Percentage of Participants With New Onset Diabetes After Transplant(up to 24 months)
- Absolute Values of Blood Pressure: Mean(Up to 24 Months)
- Absolute Values of Blood Pressure: Median(Up to 24 Months)
- Mean Changes From Baseline Values for Blood Pressure(Up to 24 Months)
- Absolute Values of Fasting Lipid Values: Mean(Up to 24 Months)
- Absolute Values of Fasting Lipid Values: Median(Up to 24 Months)
- Mean Changes From Baseline Values of Lipid Values(at months 12 and 24)