A Randomized, Open-Label, Multicenter, Parallel-Group Study of Belatacept (BMS-224818)-Based Corticosteroid-Free Regimens in Renal Transplant
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 93
- 试验地点
- 12
- 主要终点
- Number of Participants With Acute Rejection (AR) of Transplant up to 6 Months Post Transplantation - Intent to Treat (ITT) Population
研究概览
简要总结
The purpose of this clinical research study is to learn if belatacept (BMS-224818) is expected to show acceptable rates of acute rejection (AR) in steroid-free belatacept-based immunosuppressive regiments compared to a similar steroid-free tacrolimus regimen. The long-term safety and tolerability of belatacept based regimens following long-term administration in subjects who have received a kidney transplant
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Living or deceased donor renal allograft
- •Men and women, 18 to 70 years old
- •Subjects who have received a de novo kidney transplant, who have completed the initial study treatment through Month 12, and are willing to sign informed consent will be eligible to continue into the long term extension phase
排除标准
- •Pregnant or breastfeeding women
- •Epstein Barr Virus (EBV) negative serology
- •First time renal transplant with panel reactive antibody (PRA) ≥ 50% or retransplantation with PRA > 30%
- •Graft loss due to AR
- •Positive T-cell or B-cell crossmatch
- •Recipients/donors with HIV or hepatitis B/C
- •Active tuberculosis (TB)
- •Immunosuppressive therapy within 1 year of enrollment
- •UNOS ECD organs will be excluded
- •Body mass index (BMI) > 35 kg/m²
- •Subjects who have developed any malignancy (other than non-melanoma skin cancer) or other medical condition that, in the investigator's opinion, should not be treated with an experimental immunosuppressive drug like belatacept
研究组 & 干预措施
belatacept, mycophenolate mofetil (MMF)
thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months; MMF 1g twice daily(bis in die, BID)
干预措施: Thymoglobulin (Drug)
belatacept, mycophenolate mofetil (MMF)
thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months; MMF 1g twice daily(bis in die, BID)
干预措施: Belatacept (Drug)
belatacept, mycophenolate mofetil (MMF)
thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months; MMF 1g twice daily(bis in die, BID)
干预措施: Mycophenolate Mofetil (MMF) (Drug)
belatacept, sirolimus
thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months;sirolimus 5 mg/day on Day 1 (day of transplant)and continued through Day 2, dosing to be adjusted to keep pre-dose C0 levels at 7-12 ng/mL for first 6 months, followed by 5 - 10 ng/mL until 12 months.
干预措施: Thymoglobulin (Drug)
belatacept, sirolimus
thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months;sirolimus 5 mg/day on Day 1 (day of transplant)and continued through Day 2, dosing to be adjusted to keep pre-dose C0 levels at 7-12 ng/mL for first 6 months, followed by 5 - 10 ng/mL until 12 months.
干预措施: Belatacept (Drug)
belatacept, sirolimus
thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months;sirolimus 5 mg/day on Day 1 (day of transplant)and continued through Day 2, dosing to be adjusted to keep pre-dose C0 levels at 7-12 ng/mL for first 6 months, followed by 5 - 10 ng/mL until 12 months.
干预措施: Sirolimus (Drug)
tacrolimus, MMF
(IMPs as comparator regimen)thymoglobulin 1.5mg/kg for 4 days; oral tacrolimus 0.1 mg/kg/day in 2 divided doses with initial targeted trough level of 8-12 ng/mL for Days 1 - 30 with dose reduction to achieve 12 hour trough target of 5-10 ng/mL for 12 months; MMF (mycophenolate mofetil) 1g BID.
干预措施: Thymoglobulin (Drug)
tacrolimus, MMF
(IMPs as comparator regimen)thymoglobulin 1.5mg/kg for 4 days; oral tacrolimus 0.1 mg/kg/day in 2 divided doses with initial targeted trough level of 8-12 ng/mL for Days 1 - 30 with dose reduction to achieve 12 hour trough target of 5-10 ng/mL for 12 months; MMF (mycophenolate mofetil) 1g BID.
干预措施: Tacrolimus (Drug)
tacrolimus, MMF
(IMPs as comparator regimen)thymoglobulin 1.5mg/kg for 4 days; oral tacrolimus 0.1 mg/kg/day in 2 divided doses with initial targeted trough level of 8-12 ng/mL for Days 1 - 30 with dose reduction to achieve 12 hour trough target of 5-10 ng/mL for 12 months; MMF (mycophenolate mofetil) 1g BID.
干预措施: Mycophenolate Mofetil (MMF) (Drug)
结局指标
主要结局
Number of Participants With Acute Rejection (AR) of Transplant up to 6 Months Post Transplantation - Intent to Treat (ITT) Population
时间窗: Day 1 to Month 6 post-transplantation
AR is clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) greater than or equal to 25% from baseline plus one or more of the following: unexplained decreased urine output; fever, graft tenderness; SCr that remained elevated 14 days post-transplantation and clinical suspicion of AR; other reason and participant treated for episode. Day 1=transplantation. Banff 97 working classification of kidney transplant pathology: Type I=tubulointerstitial AR without arteritis (IA: interstitial infiltration with \>25% of parenchyma affected and moderate tubulitis with \>4 mononuclear cells/tubular cross section; IB: \>10 mononuclear cells; Type II vascular AR with (IA) intimal arteritis (IIA=mild - moderate; IIB=severe; Type III=severe rejection with transmural arterial changes, necrosis of smooth muscle cells.
次要结局
- Number of Participants With Acute Rejection of Transplant up to Month 12 Post Transplantation - Intent to Treat Population(Day 1 to Month 12 post transplantation)
- Number of Participants With Graft Loss or Death up to Month 6 and Month 12 Post Transplantation - Intent to Treat Population(Day 1 to Month 6 and Month 12 post transplantation)
- Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 6 - Intent to Treat Population(Day 1 up to Month 6)
- Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 12 - Intent to Treat Population(Day 1 up to Month 12)
- Number of Participants With Delayed Graft Function - Intent to Treat Population(From Day 1 up to and including Day 8 post transplantation)
- Number of Participants With New Onset Diabetes Mellitus From Baseline to Month 12 Post Transplantation - Intent to Treat Population(Baseline to Month 12)
- Number of Participants Who Used Anti-hypertension Medications at Baseline and at 12 Months Post Transplantation - Intent to Treat Population(Baseline and Month 12)
- Mean Systolic, Diastolic and Arterial Blood Pressure at Baseline and Month 12 - Intent to Treat Population(Baseline and 12 months post transplantation)
- Number of Participants Using Antihyperlipidemic Medications at Month 12 - Intent to Treat Population(Month 12)
- Mean Change From Baseline (BL) to Month 12 Post Transplantation in Lipid Values - Intent to Treat Population(Baseline to Month 12)
- Mean (Standard Deviation) in Calculated Glomerular Filtration Rate (GFR) mL/Min/1.73m^2 at Month 3, Month 6 and Month 12 Post Transplantation - Intent to Treat Population(Months 3, 6 and 12 post transplantation)
- Number of Corticosteroid-free Participants at 6 and 12 Months Post Transplantation - Intent to Treat Population(Day 1 through Month 12)
- Number of Participants Who Were Corticosteroid-free at Months 6 and 12 and Number of Participants Who Were Both Calcineurin Inhibitor-free (CNI-free)and Corticosteroid-free at Months 6 and 12 Post Transplantation - Intent to Treat Population(Day 1 to Month 12 post transplantation)
- Number of Participants With Acute Rejection of Transplant up to End of Month 48 Post Transplantation - Intent to Treat Population in Long Term Extension(End of Month 12 to end of Month 48 Post Transplantation)
- Number of Participants With Graft Loss or Death at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension(End of Month 12 to end of Long Term Extension (Year 4))
- Mean (Standard Deviation) in Calculated Glomerular Filtration Rate (GFR) mL/Min/1.73m^2 at Months 24, 36 and 48 Post Transplantation - Intent to Treat Population in Long Term Extension(Months 24, 36 and 48 post transplantation)
- Number of Corticosteroid-free Participants at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension(End of Month 12 to end of Long Term Extension (Year 4))
- Number of Participants Who Were Both Calcineurin Inhibitor-free (CNI-free)and Corticosteroid-free at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension(Months 24, 36, 48)
- Number of Participants Who Switched Between MMF and Sirolimus During Long Term Extension up to Study Completion(End of Month 12 to end of Study (Month 48))