A Phase 2, Randomized, Open-Label, Parallel Group, Multi-Center Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 323
- 试验地点
- 38
- 主要终点
- Percentage of Participants With Biopsy-confirmed Acute Rejection (BCAR) at Month 6 Assessed by Local Review
研究概览
简要总结
A study to assess the safety and efficacy of Alefacept in de novo kidney transplant patients.
详细描述
This is a 4 arm (all active) study to determine the safety and efficacy of Alefacept in de novo kidney transplant recipients.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is anticipated to receive first oral dose of tacrolimus within 48 hours of transplant procedure
- •Subject is a recipient of a de novo kidney transplant
- •Subject is a recipient of a kidney from a non-human leukocyte antigen (HLA) identical related living donor, a non-related living donor, or a deceased donor
排除标准
- •Subject has a screening (pre-operative)estimated cluster of differentiation (CD) 4+ T-cell count of < 250 cells/µL
- •Subject will receive a kidney with an anticipated cold ischemia time (CIT) of > 30 hours
- •Recipient has a positive T or B-cell cross match by investigational site's standard method of determination
- •Subject will receive a kidney from a 50-65 year old deceased donor with one of the following:
- •History of hypertension and a terminal serum creatinine > 1.5 mg/dL
- •Cerebrovascular accident as cause of death and a terminal serum creatinine > 1.5 mg/dL
- •History of hypertension and cerebrovascular accident as cause of death and a terminal serum creatinine > 1.5 mg/dL
研究组 & 干预措施
Tacrolimus/MMF/Basiliximab
Participants received tacrolimus at a starting dose of 0.20 mg/kg/day, mycophenolate mofetil (MMF) 750 or 1000 mg twice daily (BID), basiliximab administered as a 20 mg bolus injection 2 hours prior to transplantation on Day 0 and a 20 mg bolus injection on Day 3 and tapered corticosteroids for 6 months.
干预措施: tacrolimus (Drug)
Tacrolimus/MMF/Basiliximab
Participants received tacrolimus at a starting dose of 0.20 mg/kg/day, mycophenolate mofetil (MMF) 750 or 1000 mg twice daily (BID), basiliximab administered as a 20 mg bolus injection 2 hours prior to transplantation on Day 0 and a 20 mg bolus injection on Day 3 and tapered corticosteroids for 6 months.
干预措施: basiliximab (Drug)
Tacrolimus/MMF/Basiliximab
Participants received tacrolimus at a starting dose of 0.20 mg/kg/day, mycophenolate mofetil (MMF) 750 or 1000 mg twice daily (BID), basiliximab administered as a 20 mg bolus injection 2 hours prior to transplantation on Day 0 and a 20 mg bolus injection on Day 3 and tapered corticosteroids for 6 months.
干预措施: mycophenolate mofetil (Drug)
Tacrolimus/MMF/Basiliximab
Participants received tacrolimus at a starting dose of 0.20 mg/kg/day, mycophenolate mofetil (MMF) 750 or 1000 mg twice daily (BID), basiliximab administered as a 20 mg bolus injection 2 hours prior to transplantation on Day 0 and a 20 mg bolus injection on Day 3 and tapered corticosteroids for 6 months.
干预措施: Corticosteroids (Drug)
Alefacept QW/Tacrolimus/MMF
Participants received alefacept administered as a 7.5 mg intravenous (IV) bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly (QW) for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID and tapered corticosteroids for 6 months.
干预措施: Alefacept (Drug)
Alefacept QW/Tacrolimus/MMF
Participants received alefacept administered as a 7.5 mg intravenous (IV) bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly (QW) for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID and tapered corticosteroids for 6 months.
干预措施: tacrolimus (Drug)
Alefacept QW/Tacrolimus/MMF
Participants received alefacept administered as a 7.5 mg intravenous (IV) bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly (QW) for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID and tapered corticosteroids for 6 months.
干预措施: mycophenolate mofetil (Drug)
Alefacept QW/Tacrolimus/MMF
Participants received alefacept administered as a 7.5 mg intravenous (IV) bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly (QW) for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID and tapered corticosteroids for 6 months.
干预措施: Corticosteroids (Drug)
Alefacept QW/Tacrolimus
Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.20 mg/kg/day, and tapered corticosteroids for 6 months.
干预措施: Alefacept (Drug)
Alefacept QW/Tacrolimus
Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.20 mg/kg/day, and tapered corticosteroids for 6 months.
干预措施: tacrolimus (Drug)
Alefacept QW/Tacrolimus
Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.20 mg/kg/day, and tapered corticosteroids for 6 months.
干预措施: Corticosteroids (Drug)
Alefacept QOW/Tacrolimus/MMF
Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 30 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID, and tapered corticosteroids for 6 months.
干预措施: Alefacept (Drug)
Alefacept QOW/Tacrolimus/MMF
Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 30 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID, and tapered corticosteroids for 6 months.
干预措施: tacrolimus (Drug)
Alefacept QOW/Tacrolimus/MMF
Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 30 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID, and tapered corticosteroids for 6 months.
干预措施: mycophenolate mofetil (Drug)
Alefacept QOW/Tacrolimus/MMF
Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 30 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID, and tapered corticosteroids for 6 months.
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Percentage of Participants With Biopsy-confirmed Acute Rejection (BCAR) at Month 6 Assessed by Local Review
时间窗: 6 months
Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR. The Kaplan-Meier estimates at Day 182 was used for the analyses at 6 months. Lost to follow-up or patients with missing outcomes were censored at their last follow up visit.
次要结局
- Percentage of Participants With BCAR at Month 12 Assessed by Local Review(12 months)
- Graft Survival at Month 6 and Month 12(6 months and 12 months)
- Time to First T-cell Mediated BCAR Assessed by Central Review(12 months)
- Percentage of Participants With Anti-lymphocyte-treated Rejection at Months 6 and 12(6 months and 12 months)
- Percentage of Participants With Multiple Rejection Episodes at Months 6 and 12(6 months and 12 months)
- Percentage of Participants With Efficacy Failure at 6 and 12 Months Assessed by Local Review(6 months and 12 months)
- Time to First BCAR Assessed by Central Review(12 months)
- Maximum Grade of T-cell Mediated Rejection Assessed by Local Review(6 months and 12 months)
- Patient Survival at Month 6 and Month 12(6 months and 12 months)
- Change From Week 4 in Serum Creatinine at Month 6 and 12(Week 4 and Month 6 and 12)
- Time to First BCAR Assessed by Local Review(12 months)
- Maximum Grade of T-cell Mediated Rejection as Assessed by Central Review(6 months and 12 months)
- Gastrointestinal Symptom Rating Scale Scores Over Time(Months 1, 3, 6, and 12)
- Percentage of Participants With BCAR at Month 6 and 12 Assessed by Central Review(6 months and 12 months)
- Change From Week 4 in GFR by Iothalamate Clearance at Month 6(Week 4 and Month 6)
- Percentage of Participants With Efficacy Failure at 6 and 12 Months Assessed by Central Review(6 months and 12 months)
- Time to First T-cell Mediated BCAR Assessed by Local Review(12 months)
- Percentage of Participants With T-cell Mediated BCAR at Month 6 and 12 Assessed by Local Review(6 months and 12 months)
- Percentage of Participants With T-cell Mediated BCAR at Month 6 and 12 Assessed by Central Review(6 months and 12 months)
- Change From Week 4 in Glomerular Filtration Rate Estimated by the MDRD Method at Month 6 and Month 12(Week 4, Month 6 and Month 12)
- Percentage of Participants With Clinically Treated Acute Rejection at Month 6 and Month 12(6 months and 12 months)
- Percentage of Participants With Treatment Failure at Month 6 and 12(6 months and 12 months)
- Gastrointestinal Quality of Life Index Score Over Time(Months 1, 3, 6, and 12)