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The ONE Study nTreg Trial (ONEnTreg13) (ONEnTreg13)

2020年2月3日 更新者:Prof. Dr. Petra Reinke

The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation - nTregs Trial

The aim of this trial is to collect evidence of the safety of administering autologous CD4+CD25+FoxP3+ natural regulatory T cells (nTregs) to living-donor renal transplant recipients. In addition, the study will determine whether post-transplant nTregs infusion allows a tapering of conventional maintenance immunosuppression within 60 weeks after transplantation.

研究概览

详细说明

The ONE Study aims to explore the feasibility, safety and efficacy of regulatory cell therapies as adjunct immunosuppressive treatments in the context of living-donor renal transplantation.The clinical trial presented here (ONEnTreg13) will test autologous, polyclonally expanded CD4+CD25+FoxP3+ nTregs as a somatic cell-based medicinal product.

The objective of this study is to determine whether administration of nTregs to recipients of living-donor kidney transplants is safe and able to polarize the immunological response of the recipient away from graft rejection and towards graft acceptance, allowing a reduction in the doses of pharmacological maintenance immunosuppression.

研究类型

介入性

注册 (实际的)

17

阶段

  • 阶段2
  • 阶段1

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

      • Berlin、德国、13353
        • Charité University Medicine, Dept. of Nephrology and Internal Intensive Care

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 65年 (成人、年长者)

接受健康志愿者

有资格学习的性别

全部

描述

Inclusion Criteria for organ recipients:

  • Chronic renal insufficiency with a GFR < 15 ml/min, accepted by the organ transplantation conference, registered by ET (Euro Transplant) and having a positive vote from the living donor ethic commission (Lebendspendekommission) at the Berlin Medical Association.
  • Willing and able to participate in The ONE Study IM and HEC Subprojects.
  • Signed and dated written informed consent. For patients unable to read and/or write, oral informed consent observed by an independent witness is acceptable if the patient has fully understood oral information given by the Investigator. The witness should sign the consent form on behalf of the patient.

Exclusion Criteria for organ recipients:

  • Patient has previously received any tissue or organ transplant other than the planned kidney graft.
  • Known contraindication to protocol-specified treatments / medications.
  • Genetically identical to the prospective organ donor at the HLA loci, the so called "full house match" (0-0-0 mismatch).
  • Panel-Reactive Antibody (PRA) grade > 40% within last 6 months before transplantation.
  • Previous treatment with any desensitization procedure (with or without IVIg).
  • Concomitant malignancy or history of malignancy within 5 years before study entry (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of the skin).
  • Evidence of significant local or systemic infection.
  • CMV-negative recipient receiving a kidney from a CMV-positive donor. EBV-negative recipient receiving a kidney from an EBV-positive donor.
  • HIV-positive or suffering chronic viral hepatitis.
  • Significant liver disease, defined as persistently elevated AST and/or ALT levels > 2 x ULN.
  • Malignant or pre-malignant hematological conditions.
  • Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives.
  • Any condition which, according to the Investigator, would place the subject at undue risk.
  • Ongoing treatment with systemic immunosuppressive drugs at study entry.
  • Participation in another clinical trial during the study or within 28 days prior to planned study entry.
  • Female patients of childbearing potential with a positive pregnancy test at enrolment.
  • Female patients who are breast-feeding.
  • All female patients of childbearing potential unless the patient is willing to maintain a highly effective method of birth control for the duration of the study.
  • Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule.
  • Any form of drug or alcohol abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator and/or designated study personnel.
  • Patients unable to freely give their informed consent (e.g. patients under legal guardianship).
  • Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
  • Known allergy/hypersensitivity to any component of the study product.

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:治疗
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Treatment arm

Patients in ONEnTreg13 will be treated with four immunosuppressive agents, all of which are classified as an Investigational Medicinal Products (IMPs):

  • nTregs
  • Prednisolone
  • MMF
  • Tacrolimus
autologous CD4+CD25+FoxP3+ natural regulatory T cells (nTregs). nTregs will be infused at escalating doses of 0.5 x 10^6, 1 x 10^6, and 2.5-3 x 10^6 cells/kg body weight in cohorts of three patients each.

研究衡量的是什么?

主要结果指标

结果测量
大体时间
Incidence of biopsy-confirmed acute rejection (BCAR) within 60 weeks of organ transplantation
大体时间:60 weeks
60 weeks
Incidence of infectious complications associated with cell administration.
大体时间:60 weeks
60 weeks
Incidence of embolic pulmonary complications and other embolic events.
大体时间:60 weeks
60 weeks
Incidence of immune responses resulting in anaphylactic reactions, cardiovascular compromise or other acute organ failure.
大体时间:60 weeks
60 weeks
Biochemical disturbances associated with the cell infusion.
大体时间:60 weeks
60 weeks
Over-suppression of the immune system assessed by the incidence of opportunistic infections, especially, CMV, EBV and polyoma virus.
大体时间:60 weeks
60 weeks
Over-suppression of the immune system assessed by the incidence of neoplasia.
大体时间:60 weeks
60 weeks

次要结果测量

结果测量
措施说明
大体时间
根据组织病理学结果接受亚临床急性排斥反应治疗的患者的发生率
大体时间:60周
60周
Prevention of acute rejection will be secondarily assessed by measuring
大体时间:60 weeks
i) time to first acute rejection episode ii) severity of acute rejection episodes based on response to treatment and histological scoring iii) the level of total immunosuppression drugs at the final trial visit.
60 weeks
Prevention of chronic graft dysfunction (chronic rejection or IF/TA) will be assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures.
大体时间:60 weeks
60 weeks
Incidence of post-transplant dialysis, inclusion on the transplant waiting list or retransplantation following graft loss through rejection (acute or chronic).
大体时间:60 weeks
60 weeks
Avoidance of drug-related complications by immunosuppressant reduction will be assessed by the incidence of reported adverse drug reactions.
大体时间:60 weeks
60 weeks

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。

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。

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

2015年2月1日

初级完成 (实际的)

2017年11月1日

研究完成 (实际的)

2017年11月1日

研究注册日期

首次提交

2015年2月18日

首先提交符合 QC 标准的

2015年2月19日

首次发布 (估计)

2015年2月25日

研究记录更新

最后更新发布 (实际的)

2020年2月5日

上次提交的符合 QC 标准的更新

2020年2月3日

最后验证

2020年2月1日

更多信息

与本研究相关的术语

其他研究编号

  • ONEnTreg13

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.

autologous CD4+CD25+FoxP3+ natural regulat. T cells (nTregs)的临床试验

3
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