Brook Matthew Oliver, Hester Joanna, Petchey William, Rombach Ines, Dutton Susan, Bottomley Matthew James, Black Joanna, Abdul-Wahab Seetha, Bushell Andrew, Lombardi Giovanna, Wood Kathryn, Friend Peter, Harden Paul, Issa Fadi
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
Oxford Transplant Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
BMJ Open. 2022 Apr 15;12(4):e061864. doi: 10.1136/bmjopen-2022-061864.
Regulatory T cell (Treg) therapy has been demonstrated to facilitate long-term allograft survival in preclinical models of transplantation and may permit reduction of immunosuppression and its associated complications in the clinical setting. Phase 1 clinical trials have shown Treg therapy to be safe and feasible in clinical practice. Here we describe a protocol for the TWO study, a phase 2b randomised control trial of Treg therapy in living donor kidney transplant recipients that will confirm safety and explore efficacy of this novel treatment strategy.
60 patients will be randomised on a 1:1 basis to Treg therapy (TR001) or standard clinical care (control). Patients in the TR001 arm will receive an infusion of autologous polyclonal ex vivo expanded Tregs 5 days after transplantation instead of standard monoclonal antibody induction. Maintenance immunosuppression will be reduced over the course of the post-transplant period to low-dose tacrolimus monotherapy. Control participants will receive a standard basiliximab-based immunosuppression regimen with long-term tacrolimus and mycophenolate mofetil immunosuppression. The primary endpoint is biopsy proven acute rejection over 18 months; secondary endpoints include immunosuppression burden, chronic graft dysfunction and drug-related complications.
Ethical approval has been provided by the National Health Service Health Research Authority South Central-Oxford A Research Ethics Committee (reference 18/SC/0054). The study also received authorisation from the UK Medicines and Healthcare products Regulatory Agency and is being run in accordance with the principles of Good Clinical Practice, in collaboration with the registered trials unit Oxford Clinical Trials Research Unit. Results from the TWO study will be published in peer-reviewed scientific/medical journals and presented at scientific/clinical symposia and congresses.
ISRCTN: 11038572; Pre-results.
调节性T细胞（Treg）疗法已在移植临床前模型中被证明可促进同种异体移植物的长期存活，并可能在临床环境中减少免疫抑制及其相关并发症。1期临床试验表明Treg疗法在临床实践中是安全可行的。在此，我们描述了TWO研究的方案，这是一项针对活体供肾移植受者的Treg疗法2b期随机对照试验，将确认这种新型治疗策略的安全性并探索其疗效。
60名患者将按1:1的比例随机分为Treg疗法组（TR001）或标准临床护理组（对照组）。TR001组的患者将在移植后5天接受自体多克隆体外扩增Treg的输注，而不是标准的单克隆抗体诱导治疗。在移植后的一段时间内，维持免疫抑制将减少至高剂量他克莫司单药治疗。对照组参与者将接受基于巴利昔单抗的标准免疫抑制方案，长期使用他克莫司和霉酚酸酯进行免疫抑制。主要终点是18个月内活检证实的急性排斥反应；次要终点包括免疫抑制负担、慢性移植物功能障碍和药物相关并发症。
英国国家医疗服务体系健康研究管理局中南牛津A研究伦理委员会已提供伦理批准（参考编号18/SC/0054）。该研究还获得了英国药品和医疗产品监管局的授权，并按照良好临床实践原则，与注册试验单位牛津临床试验研究单位合作进行。TWO研究的结果将发表在同行评审的科学/医学期刊上，并在科学/临床研讨会和大会上展示。
ISRCTN：11038572；预结果。
