Transplantation Without Overimmunosuppression (TWO) study protocol: a phase 2b randomised controlled single-centre trial of regulatory T cell therapy to facilitate immunosuppression reduction in living donor kidney transplant recipients.
Transplantation Without Overimmunosuppression (TWO) study protocol: a phase 2b randomised controlled single-centre trial of regulatory T cell therapy to facilitate immunosuppression reduction in living donor kidney transplant recipients.
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DOI：
10.1136/bmjopen-2022-061864
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发表时间：
2022-04-15
期刊：
影响因子：
2.9
通讯作者：
Issa, Fadi
中科院分区：
文献类型：
--
作者：
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
调节性 T 细胞 (Treg) 疗法已被证明可促进临床前移植模型中同种异体移植物的长期存活，并可能减少临床环境中的免疫抑制及其相关并发症。一期临床试验表明Treg疗法在临床实践中是安全可行的。在这里，我们描述了 TWO 研究的方案，这是一项在活体肾移植受者中进行 Treg 治疗的 2b 期随机对照试验，该试验将确认这种新型治疗策略的安全性并探索其有效性。 60 名患者将按照 1:1 的比例随机分配接受 Treg 治疗 (TR001) 或标准临床护理（对照）。 TR001 组的患者将在移植后 5 天接受自体多克隆离体扩增的 Tregs 输注，而不是标准的单克隆抗体诱导。在移植后期间，维持性免疫抑制将减少为低剂量他克莫司单一疗法。对照参与者将接受基于巴利昔单抗的标准免疫抑制方案，并长期使用他克莫司和吗替麦考酚酯免疫抑制。主要终点是活检证实超过 18 个月的急性排斥反应；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。伦理批准已由国家卫生服务健康研究局中南部—牛津 A 研究伦理委员会提供（参考号 18/SC/0054）。该研究还获得了英国药品和保健品监管机构的授权，并与注册试验单位牛津临床试验研究单位合作，按照良好临床实践的原则进行。这两项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发表。 ISRCTN：11038572；预结果。
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.
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影响因子：
2.7
作者：
Levitsky, Josh;Leventhal, Joseph R.;Mathew, James M.
通讯作者：
Mathew, James M.
DOI：
10.1136/bmj.m3734
发表时间：
2020-10-21
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Roemhild A;Otto NM;Moll G;Abou-El-Enein M;Kaiser D;Bold G;Schachtner T;Choi M;Oellinger R;Landwehr-Kenzel S;Juerchott K;Sawitzki B;Giesler C;Sefrin A;Beier C;Wagner DL;Schlickeiser S;Streitz M;Schmueck-Henneresse M;Amini L;Stervbo U;Babel N;Volk HD;Reinke P
通讯作者：
Reinke P
DOI：
10.1016/j.omtm.2018.01.006
发表时间：
2018-03-16
期刊：
Molecular therapy. Methods & clinical development
影响因子：
--
作者：
Fraser H;Safinia N;Grageda N;Thirkell S;Lowe K;Fry LJ;Scottá C;Hope A;Fisher C;Hilton R;Game D;Harden P;Bushell A;Wood K;Lechler RI;Lombardi G
通讯作者：
Lombardi G
影响因子：
158.5
作者：
Ekberg, Henrik;Tedesco-Silva, Helio;Halloran, Philip F.
通讯作者：
Halloran, Philip F.
DOI：
10.1016/s0140-6736(20)30167-7
发表时间：
2020-05-23
期刊：
Lancet (London, England)
影响因子：
--
作者：
Sawitzki B;Harden PN;Reinke P;Moreau A;Hutchinson JA;Game DS;Tang Q;Guinan EC;Battaglia M;Burlingham WJ;Roberts ISD;Streitz M;Josien R;Böger CA;Scottà C;Markmann JF;Hester JL;Juerchott K;Braudeau C;James B;Contreras-Ruiz L;van der Net JB;Bergler T;Caldara R;Petchey W;Edinger M;Dupas N;Kapinsky M;Mutzbauer I;Otto NM;Öllinger R;Hernandez-Fuentes MP;Issa F;Ahrens N;Meyenberg C;Karitzky S;Kunzendorf U;Knechtle SJ;Grinyó J;Morris PJ;Brent L;Bushell A;Turka LA;Bluestone JA;Lechler RI;Schlitt HJ;Cuturi MC;Schlickeiser S;Friend PJ;Miloud T;Scheffold A;Secchi A;Crisalli K;Kang SM;Hilton R;Banas B;Blancho G;Volk HD;Lombardi G;Wood KJ;Geissler EK
通讯作者：
Geissler EK