Efficacy and Safety of Alefacept in Combination With Tacrolimus, Mycophenolate Mofetil and Steroids in de Novo Kidney Transplantation - a Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 218
- 主要终点
- Percentage of Participants With Biopsy-confirmed Acute T-cell Mediated Rejection at Month 6 Assessed by Local Review
研究概览
简要总结
The purpose of this study is to determine whether alefacept is effective and well tolerated when used with a combination of tacrolimus, mycophenolate mofetil and steroids versus a combination therapy of placebo, tacrolimus and steroids in the prevention of kidney transplant rejection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject with end stage kidney disease who is a suitable candidate for primary kidney transplantation or retransplantation
- •Male or female subject at least 18 years of age and younger than 65 years
- •Subject receiving a kidney transplant from a non-human leucocyte antigen (HLA) identical living donor or deceased HLA identical/non-HLA identical donor between 5 and 59 years of age with compatible ABO blood type (Blood group system A, B, AB and 0)
排除标准
- •Subject has a panel reactivity antibody grade > 20% in the previous 6 months and/or had had a previous graft survival shorter than 1 year due to immunological reasons
- •Subject received a kidney transplant from a non-heart beating donor
- •Subject has received a kidney transplant from a 50 - 59 year old donor with two of the following three factors: history of hypertension, cerebrovascular accident as cause of death, final pre-procurement serum creatinine > 1.5 mg/dL (united network for organ sharing [UNOS] expanded criteria donor)
- •Cold ischemia time of the donor kidney is ≥ 30 hours
研究组 & 干预措施
Placebo
Participants received placebo administered intra-operatively as an intravenous (IV) bolus on Day 0, another IV bolus on Day 3 and weekly subcutaneous injections thereafter for 12 weeks. Participants also received tacrolimus, mycophenolate mofetil (MMF) and steroid treatment.
干预措施: placebo (Drug)
Placebo
Participants received placebo administered intra-operatively as an intravenous (IV) bolus on Day 0, another IV bolus on Day 3 and weekly subcutaneous injections thereafter for 12 weeks. Participants also received tacrolimus, mycophenolate mofetil (MMF) and steroid treatment.
干预措施: Tacrolimus (Drug)
Placebo
Participants received placebo administered intra-operatively as an intravenous (IV) bolus on Day 0, another IV bolus on Day 3 and weekly subcutaneous injections thereafter for 12 weeks. Participants also received tacrolimus, mycophenolate mofetil (MMF) and steroid treatment.
干预措施: Mycophenolate Mofetil (Drug)
Placebo
Participants received placebo administered intra-operatively as an intravenous (IV) bolus on Day 0, another IV bolus on Day 3 and weekly subcutaneous injections thereafter for 12 weeks. Participants also received tacrolimus, mycophenolate mofetil (MMF) and steroid treatment.
干预措施: Steroids (Drug)
Alefacept
Participants received 7.5 mg alefacept administered intra-operatively as an IV bolus on Day 0, another 7.5 mg IV bolus on Day 3, and weekly subcutaneous injections of 15 mg alefacept thereafter for 12 weeks. Participants also received tacrolimus, MMF and steroid treatment.
干预措施: Alefacept (Drug)
Alefacept
Participants received 7.5 mg alefacept administered intra-operatively as an IV bolus on Day 0, another 7.5 mg IV bolus on Day 3, and weekly subcutaneous injections of 15 mg alefacept thereafter for 12 weeks. Participants also received tacrolimus, MMF and steroid treatment.
干预措施: Tacrolimus (Drug)
Alefacept
Participants received 7.5 mg alefacept administered intra-operatively as an IV bolus on Day 0, another 7.5 mg IV bolus on Day 3, and weekly subcutaneous injections of 15 mg alefacept thereafter for 12 weeks. Participants also received tacrolimus, MMF and steroid treatment.
干预措施: Mycophenolate Mofetil (Drug)
Alefacept
Participants received 7.5 mg alefacept administered intra-operatively as an IV bolus on Day 0, another 7.5 mg IV bolus on Day 3, and weekly subcutaneous injections of 15 mg alefacept thereafter for 12 weeks. Participants also received tacrolimus, MMF and steroid treatment.
干预措施: Steroids (Drug)
结局指标
主要结局
Percentage of Participants With Biopsy-confirmed Acute T-cell Mediated Rejection at Month 6 Assessed by Local Review
时间窗: 6 months
Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification: * Grade IA: significant interstitial infiltration (\>25% parenchyma affected) and foci of moderate tubulitis; * Grade IB: significant interstitial infiltration (\>25% parenchyma affected) and foci of severe tubulitis; * Grade IIA: mild to moderate intimal arteritis; * Grade IIB: severe intimal arteritis comprising \>25% of the luminal area; * Grade III: "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocyte inflammation. A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1. The Kaplan-Meier estimate of biopsy-confirmed acute T-cell mediated rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
次要结局
- Percentage of Participants With Biopsy Confirmed Antibody-Mediated Acute Rejection at Month 6(6 months)
- Percentage of Participants With Biopsy Confirmed Acute Rejection (T-Cell Mediated or Antibody Mediated) at Month 6(6 months)
- Percentage of Participants With Acute Rejection Diagnosed by Signs and Symptoms at Month 6(6 months)
- Maximum Histological Grade of All Biopsies After Local Review(6 months)
- Percentage of Participants With Biopsy Confirmed Acute Mixed T-Cell Mediated and Antibody-Mediated Rejection at Month 6(6 months)
- Percentage of Participants With Efficacy Failure at Month 6(6 months)
- Percentage of Participants With Clinically Treated Acute Rejection at Month 6(6 months)
- Percentage of Participants With Steroid-resistant Acute Rejection at Month 6(6 months)
- Percentage of Participants With Biopsy-Confirmed Acute T-cell Mediated Rejection as Assessed by Central Review at Month 6(6 months)
- Patient Survival(6 months)
- Graft Survival(6 months)
- Percentage of Participants With Anti-Lymphocyte Antibody Therapy for Treatment of Rejection at Month 6(6 months)
- Change From Month 1 in Serum Creatinine(Month 1, 3, and 6)
- GFR Measured by Iothalamate Clearance at Month 6(Month 6)
- Percentage of Participants With Treatment Failure at Month 6(6 months)
- Change From Month 1 in Glomerular Filtration Rate (GFR)(Month 1, 3, and 6)
- Change From Month 1 in Creatinine Clearance(Month 1, 3, and 6)
- Percentage of Participants With Delayed Graft Function(1 week)
- Number of Participants With Adverse Events(6 Months)