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A Study to Assess the Efficacy and Safety of Alefacept in Kidney Transplant Recipients

2016年1月5日 更新者：Astellas Pharma Inc

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

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.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

218

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 匈牙利
      • Budapest、匈牙利、1082
  • 奥地利
      • Vienna、奥地利、1090
  • 德国
      • Bochum、德国、44892
      • Regensburg、德国、93053
  • 意大利
      • Bologna、意大利、40138
      • Padova、意大利、35128
      • Rome、意大利、00168
      • Siena、意大利、53100
  • 捷克共和国
      • Praha、捷克共和国、140 21
  • 比利时
      • Bruxelles、比利时、1070
      • Bruxelles、比利时、1200
      • Gent、比利时、9000
      • Leuven、比利时、3000
      • Liege、比利时、4000
  • 法国
      • Creteil、法国、94010
      • Le Kremlin Bicetre Cedex、法国、94275
      • Montpellier、法国、34295
      • Nantes Cedex 1、法国、44093
      • Nice Cedex 1、法国、6002
      • Paris、法国、75475
      • Toulouse Cedex、法国、31054
  • 波兰
      • Bydgoszcz、波兰、85-094
      • Poznan、波兰、60-479
      • Szczecin、波兰、70-111
  • 瑞典
      • Goteborg、瑞典、41345
      • Uppsala、瑞典、75185
  • 英国
      • Manchester、英国、M13 9WL
  • 荷兰
      • Maastricht、荷兰、6229
  • 西班牙
      • Barcelona、西班牙、8036
      • Llobregat、西班牙、8907
      • Madrid、西班牙、28041
      • Malaga、西班牙、29010
      • Santander、西班牙、39008

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 64年 (成人)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：预防
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
安慰剂比较：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.
药品：placebo
IV and subcutaneous injection
药品：Tacrolimus
The initial daily dose was 0.2 mg/kg orally given in 2 doses commencing 24 hours after completion of surgery.
药品：Mycophenolate Mofetil
Mycophenolic mofetil was administered as 750 mg twice per day orally
药品：Steroids

Methylprednisolone or equivalent:

Day 0: 500 - 1000 mg IV bolus Day 1: 125 - 250 mg IV bolus

Prednisone or equivalent:

Days 2 - 14: 20 - 30 mg orally Days 15 - 28: 10 - 20 mg orally Days 29 - 60: 10 - 15 mg orally Days 61 onwards: 5 - 10 mg orally
实验性的：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.
药品：Tacrolimus
The initial daily dose was 0.2 mg/kg orally given in 2 doses commencing 24 hours after completion of surgery.
药品：Mycophenolate Mofetil
Mycophenolic mofetil was administered as 750 mg twice per day orally
药品：Steroids

Methylprednisolone or equivalent:

Day 0: 500 - 1000 mg IV bolus Day 1: 125 - 250 mg IV bolus

Prednisone or equivalent:

Days 2 - 14: 20 - 30 mg orally Days 15 - 28: 10 - 20 mg orally Days 29 - 60: 10 - 15 mg orally Days 61 onwards: 5 - 10 mg orally

药品：Alefacept
IV and subcutaneous injection
其他名称：
  • 阿米维夫

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Percentage of Participants With Biopsy-confirmed Acute T-cell Mediated Rejection at Month 6 Assessed by Local Review
大体时间：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.
6 months

次要结果测量

结果测量
措施说明
大体时间
Percentage of Participants With Biopsy Confirmed Antibody-Mediated Acute Rejection at Month 6
大体时间：6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification:

Acute antibody-mediated rejection - documented anti-donor antibody ('suspicious for' if antibody not demonstrated):

  • Grade I: acute tubular necrosis-like - complement split product positive (C4d+), minimal inflammation;
  • Grade II: capillary-margination and/or thromboses, C4d+
  • Grade III: arterial - v3, C4d+.

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 antibody-mediated acute 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.
6 months
Percentage of Participants With Biopsy Confirmed Acute Rejection (T-Cell Mediated or Antibody Mediated) at Month 6
大体时间：6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification. 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 or antibody-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.
6 months
Percentage of Participants With Biopsy Confirmed Acute Mixed T-Cell Mediated and Antibody-Mediated Rejection at Month 6
大体时间：6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification. 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 mixed T-cell mediated and antibody-mediated rejections 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.
6 months
Percentage of Participants With Acute Rejection Diagnosed by Signs and Symptoms at Month 6
大体时间：6 months
Acute rejection diagnosed by signs and symptoms, including biopsy-confirmed or suspected (not confirmed by biopsy - i.e. no biopsy was performed or biopsy did not confirm an acute T-cell mediated rejection). The Kaplan-Meier estimate of acute rejection diagnosed by signs and symptoms 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.
6 months
Percentage of Participants With Clinically Treated Acute Rejection at Month 6
大体时间：6 months
Patients who received immunosuppressive medications for the treatment of suspected or biopsy-confirmed acute rejections were considered to have a clinically-treated acute rejection. The Kaplan-Meier estimate of clinically treated acute 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.
6 months
Percentage of Participants With Steroid-resistant Acute Rejection at Month 6
大体时间：6 months

A steroid-resistant acute rejection is defined as a rejection episode which did not resolve following treatment with corticosteroids. In the case that a rejection episode was not treated with corticosteroids first but only with antibodies, it was included in this category.

The Kaplan-Meier estimate of steroid-resistant acute 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.
6 months
Percentage of Participants With Biopsy-Confirmed Acute T-cell Mediated Rejection as Assessed by Central Review at Month 6
大体时间：6 months

Biopsies were graded by the central reviewer according to the Banff 97/05 updated histological classification. 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.
6 months
Patient Survival
大体时间：6 months
Patient survival is any participant known to be alive at Month 6. The Kaplan-Meier estimate of patient survival within the first 6 months following transplantation is reported. Participants lost to follow-up were censored at the time of last assessment.
6 months
Graft Survival
大体时间：6 months

Graft survival was defined as any participant who was known to have a functioning graft (i.e., not graft loss) at 6 months. Graft loss is defined as re-transplantation, nephrectomy, death or as dialysis ongoing at end of study or at discontinuation of the participant unless superseded by follow-up information.

The Kaplan-Meier estimate of graft survival within the first 6 months following transplantation is reported. Participants lost to follow-up were censored at the time of last assessment.
6 months
Maximum Histological Grade of All Biopsies After Local Review
大体时间：6 months

The grade of acute rejection was classified according to Banff 97/05 updated version. If a patient had more than 1 rejection episode, the episode with the most severe grade was used.

Acute T-cell mediated rejection:

  • 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.

Acute antibody-mediated rejection:

  • Grade I: acute tubular necrosis-like - complement split product positive (C4d+), minimal inflammation;
  • Grade II: capillary-margination and/or thromboses, C4d+
  • Grade III: arterial - v3, C4d+.
6 months
Percentage of Participants With Anti-Lymphocyte Antibody Therapy for Treatment of Rejection at Month 6
大体时间：6 months
The Kaplan-Meier estimate of anti-lymphocyte antibody therapy for acute rejection (clinically-treated or biopsy-confirmed) 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.
6 months
Change From Month 1 in Serum Creatinine
大体时间：Month 1, 3, and 6
Month 1, 3, and 6
Change From Month 1 in Glomerular Filtration Rate (GFR)
大体时间：Month 1, 3, and 6
The GFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.
Month 1, 3, and 6
Change From Month 1 in Creatinine Clearance
大体时间：Month 1, 3, and 6
The creatinine clearance was calculated according to the Cockcroft-Gault formula.
Month 1, 3, and 6
GFR Measured by Iothalamate Clearance at Month 6
大体时间：Month 6
GFR measured using the iothalamate clearance method and determined by a central laboratory.
Month 6
Percentage of Participants With Efficacy Failure at Month 6
大体时间：6 months

Efficacy failure is defined as death, graft loss, biopsy-confirmed acute T-cell mediated rejection assessed by local reading or lost to follow-up.

The Kaplan-Meier estimate of efficacy failure within the first 6 months following transplantation is reported.
6 months
Percentage of Participants With Delayed Graft Function
大体时间：1 week
Delayed graft function was defined as the requirement for dialysis within the first week post-transplant.
1 week
Percentage of Participants With Treatment Failure at Month 6
大体时间：6 months
Treatment failure is defined as efficacy failure (death, graft loss, biopsy-confirmed acute T-cell mediated rejection assessed by local reading, lost to follow-up) or early discontinuation of alefacept/placebo at any time (during the 12-week administration period) for any reason. The Kaplan-Meier estimate of treatment failure 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.
6 months
Number of Participants With Adverse Events
大体时间：6 Months

Causally related was defined as adverse events (AEs) assessed by the Investigator as possibly or probably related to study drug or records where the relationship was missing.

A serious adverse event (SAE) was any untoward medical occurrence that, at any dose:

  • Resulted in death.
  • Was life-threatening.
  • Resulted in persistent or significant disability/incapacity.
  • Resulted in congenital anomaly or birth defect.
  • Required patient hospitalization or led to prolongation of hospitalization
  • Was considered a medically important event.

All rejections and any BK virus, Epstein Barr virus and/or cytomegalovirus infection had to be reported as an SAE
6 Months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Astellas Pharma Inc

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2007年12月1日

初级完成 (实际的)

2009年9月1日

研究完成 (实际的)

2009年9月1日

研究注册日期

首次提交

2008年2月6日

首先提交符合 QC 标准的

2008年2月6日

首次发布 (估计)

2008年2月18日

研究记录更新

最后更新发布 (估计)

2016年2月4日

上次提交的符合 QC 标准的更新

2016年1月5日

最后验证

2016年1月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 0485-CL-E201
  • 2007-002092-14 (EudraCT编号)

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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