The true functional differences between alternative cell preparations will be evaluated in a Phase I/II clinical trial in living donor renal transplant recipients in order to assess the safety and potential of the different licensed haematopoietic cell therapy treatments in reducing the need for maintenance immunosuppression. Nephrologists from all the academic institutions involved in the project will finalise specific details of the trial, such as target drug levels and protocol biopsy schedules. An ethical advisory board (PEC) will also be put in place to hear and judge ethical concerns before the final protocol is submitted to local ethics committees for approval.
Evaluation of the trial will be critical. An innovative electronic case report form (eCRF) data capture system for the trial will be developed with the help of the clinical research organisation ClinIT. With this approach, data from the clinical trial at each of the sites will be entered into a central database for evaluation of safety and efficacy. An important part of the patient evaluation will be to set up biomarker testing that will provide valuable information about the anti-donor response of the transplant recipient; the eCRF will be designed such that the immune monitoring data can be directly incorporated into the patient eCRF. Finally, trial safety will be evaluated with a pharmacovigilance and clinical monitoring team. The partner in Regensburg will coordinate these activities. In addition, a data safety monitoring board (DSMB) will be established to oversee the trial results. Moreover, Immunomonitoring constitutes an important part of the ONE Study clinical trial. The monitoring effort will be coordinated by Prof. H.D. Volk of the Charité, Berlin. By screening for reactive markers of rejection, we aim to improve patient safety; secondly, we hope to use predictive markers of tolerance to indicate a beneficial effect of cell therapy; thirdly, we hope to gain some biologic insight into the effects of each of the cell therapies.
Knowing the fate of immunoregulatory cells in the recipient after administration is key to understanding their mechanisms of action. As part of The ONE Study project, we will pursue a very innovative approach to tracking of blood cells, whereby manufactured cell products will be labelled with combinations of rare earth metals which can be tracked in blood and biopsy material using laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS; Electro Scientific Industries and the University of Loughborough). This technology will be used to trace cell products from the different sites that have been licensed for use in our clinical study. Commercial exploitation of this technology is an expected result of the project.