Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trial
Introduction Accumulating evidence suggests that the adoptive transfer of ex vivo expanded regulatory T cells (Treg) may overcome colitogenic immune responses in patients with inflammatory bowel diseases. The objective of the ER-TREG 01 trial is to assess safety and tolerability of a single infusion...
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BMJ Publishing Group
2021-12-01
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| Online Access: | https://bmjopen.bmj.com/content/11/12/e049208.full |
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| author | Carola Berking Raja Atreya Markus F Neurath Sebastian Zundler Britta Siegmund Gerold Schuler Francesco Vitali Caroline J Voskens Diane Stoica Susanne Roessner Marita Rosenberg Manuel Wiesinger Jutta Wunder Beatrice Schuler-Thurner |
| author_facet | Carola Berking Raja Atreya Markus F Neurath Sebastian Zundler Britta Siegmund Gerold Schuler Francesco Vitali Caroline J Voskens Diane Stoica Susanne Roessner Marita Rosenberg Manuel Wiesinger Jutta Wunder Beatrice Schuler-Thurner |
| author_sort | Carola Berking |
| collection | DOAJ |
| description | Introduction Accumulating evidence suggests that the adoptive transfer of ex vivo expanded regulatory T cells (Treg) may overcome colitogenic immune responses in patients with inflammatory bowel diseases. The objective of the ER-TREG 01 trial is to assess safety and tolerability of a single infusion of autologous ex vivo expanded Treg in adults with ulcerative colitis.Methods and analysis The study is designed as a single-arm, fast-track dose-escalation trial. The study will include 10 patients with ulcerative colitis. The study intervention consists of (1) a baseline visit; (2) a second visit that includes a leukapheresis to generate the investigational medicinal product, (3) a third visit to infuse the investigational medicinal product and (4) five subsequent follow-up visits within the next 26 weeks to assess safety and tolerability. Patients will intravenously receive a single dose of 0.5×106, 1×106, 2×106, 5×106 or 10×106 autologous Treg/kg body weight. The primary objective is to define the maximum tolerable dose of a single infusion of autologous ex vivo expanded Treg. Secondary objectives include the evaluation of safety of one single infusion of autologous ex vivo expanded Treg, efficacy assessment and accompanying immunomonitoring to measure Treg function in the peripheral blood and intestinal mucosa.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany (number 417_19 Az). In addition, the study was approved by the Paul-Ehrlich Institute, Federal Institute for Vaccines and Biomedicines, Langen, Germany (number 3652/01). The study is funded by the German Research Foundation (DFG, KFO 257 project 08 and SFB/TransRegio 241 project C04). The trial will be conducted in compliance with this study protocol, the Declaration of Helsinki, Good Clinical Practice and Good Manufacturing Practice. The results will be published in peer-reviewed scientific journals and disseminated in scientific conferences and media.Trial registration number NCT04691232. |
| format | Article |
| id | doaj-art-f95743919b5946788d4f8f3c106c9653 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-f95743919b5946788d4f8f3c106c96532024-12-10T05:00:11ZengBMJ Publishing GroupBMJ Open2044-60552021-12-01111210.1136/bmjopen-2021-049208Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trialCarola Berking0Raja Atreya1Markus F Neurath2Sebastian Zundler3Britta Siegmund4Gerold Schuler5Francesco Vitali6Caroline J Voskens7Diane Stoica8Susanne Roessner9Marita Rosenberg10Manuel Wiesinger11Jutta Wunder12Beatrice Schuler-Thurner13Department of Dermatology, FAU Erlangen-Nürnberg, Erlangen, Germany6 Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDepartment of Medicine 1, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany1 Department of Gastroenterology, Infectiology and Rheumatology, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, GermanyHautklinik, Universitätsklinikum Erlangen, Erlangen, Germany1 Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universitat Erlangen-Nürnberg, Erlangen, Bayern, GermanyDepartment of Dermatology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, GermanyDepartment of Dermatology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, GermanyDepartment of Dermatology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, GermanyDepartment of Dermatology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDeutsches Zentrum für Immuntherapie (DZI), Erlangen, GermanyHautklinik, Universitätsklinikum Erlangen, Erlangen, GermanyIntroduction Accumulating evidence suggests that the adoptive transfer of ex vivo expanded regulatory T cells (Treg) may overcome colitogenic immune responses in patients with inflammatory bowel diseases. The objective of the ER-TREG 01 trial is to assess safety and tolerability of a single infusion of autologous ex vivo expanded Treg in adults with ulcerative colitis.Methods and analysis The study is designed as a single-arm, fast-track dose-escalation trial. The study will include 10 patients with ulcerative colitis. The study intervention consists of (1) a baseline visit; (2) a second visit that includes a leukapheresis to generate the investigational medicinal product, (3) a third visit to infuse the investigational medicinal product and (4) five subsequent follow-up visits within the next 26 weeks to assess safety and tolerability. Patients will intravenously receive a single dose of 0.5×106, 1×106, 2×106, 5×106 or 10×106 autologous Treg/kg body weight. The primary objective is to define the maximum tolerable dose of a single infusion of autologous ex vivo expanded Treg. Secondary objectives include the evaluation of safety of one single infusion of autologous ex vivo expanded Treg, efficacy assessment and accompanying immunomonitoring to measure Treg function in the peripheral blood and intestinal mucosa.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany (number 417_19 Az). In addition, the study was approved by the Paul-Ehrlich Institute, Federal Institute for Vaccines and Biomedicines, Langen, Germany (number 3652/01). The study is funded by the German Research Foundation (DFG, KFO 257 project 08 and SFB/TransRegio 241 project C04). The trial will be conducted in compliance with this study protocol, the Declaration of Helsinki, Good Clinical Practice and Good Manufacturing Practice. The results will be published in peer-reviewed scientific journals and disseminated in scientific conferences and media.Trial registration number NCT04691232.https://bmjopen.bmj.com/content/11/12/e049208.full |
| spellingShingle | Carola Berking Raja Atreya Markus F Neurath Sebastian Zundler Britta Siegmund Gerold Schuler Francesco Vitali Caroline J Voskens Diane Stoica Susanne Roessner Marita Rosenberg Manuel Wiesinger Jutta Wunder Beatrice Schuler-Thurner Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trial BMJ Open |
| title | Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trial |
| title_full | Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trial |
| title_fullStr | Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trial |
| title_full_unstemmed | Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trial |
| title_short | Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trial |
| title_sort | safety and tolerability of a single infusion of autologous ex vivo expanded regulatory t cells in adults with ulcerative colitis er treg 01 protocol of a phase 1 open label fast track dose escalation clinical trial |
| url | https://bmjopen.bmj.com/content/11/12/e049208.full |
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