Ethical and Safety Monitoring & Clinical Trial Summary

Two key committees have oversight of ethical issues and safety monitoring during the EVERREST project and clinical trial. An independent ethics advisory committee will monitor ethical issues throughout the duration of the project and a data safety monitoring board will report on the safety and conduct of the trial.The Independent Ethics Advisory Committee aims to meet every 6 months in the first 18 months, and then every 9 months thereafter. At the start of the project the EAC will agree on an ethical framework for evaluating the project. They will examine the findings of WP2 (Bioethics), consider data from the toxicology study and submit a report to the Commission on their findings. For the remainder of the project they will hold regular meetings (every 9-12 months) to provide input to WP4 (Ethical and Regulatory Approval of the Study) and to evaluate ethical issues relating to any adverse events during the Phase I/IIa safety/efficacy trial. The EAC had its first meeting in September 2013. Details of all committee members, their affiliations and expertise can be found here.

The Independent Ethics Advisory Committee at its first meeting (London, Sept 2013)
From left to right: Christoph Rehmann-Sutter, Mark Sheehan, Hilde Lindemann, Maria Sheppard, Jackie Leach Scully, Richard Ashcroft, Sorcha Ui Chonnachtaigh
(note: Maria Sheppard and Richard Ashcroft are part of the EVERREST project team from Queen Mary and Westfield College, London).

The Data Safety Monitoring Board (DMSB) was appointed by UCL (the sponsor of the EVERREST clinical trial) and had their first meeting in September 2013. They are responsible for overseeing patient safety and the conduct of the clinical trial. They will consider the clinical trial protocol in detail, decide how they might respond to hypothetical situations, develop and agree a charter governing their remit and conduct, and agree the stopping rules for the trial. The DSMB will also agree a list of safety issues and unexpected serious adverse events that will be used to review the phase I/IIa trial once it is underway. If a serious concern with the safety of the patients in the trial arises, the DSMB may recommend early termination of the study. Details of all committee members, their affiliations and expertise can be found here.

The EVERREST Data Safety Monitoring Board at their first meeting (UCL, Sept 2013)
From left to right: Andy Baker, Zarko Alfirevic, Marc Sapoval, and Adrian Thrasher.

The Clinical Trial proposes using adenoviral vector VEGF D short-form gene therapy given to pregnant patients (mothers) with severe early onset placental insufficiency to firstly assess its safety and secondly to assess if it increases uterine artery blood flow, fetal growth and neonatal outcomes. More information about placental insufficiency and gene therapy can be found on the fetal growth restriction Tab of this website. The type of gene therapy proposed for the EVERREST Clinical trial has not been used in pregnant women or adults before. However, very similar gene therapies, using the same inactivated virus and similar VEGF growth factors, have been used in adults in several clinical trials for heart disease and peripheral vascular disease, with at least 10 years of follow up data. The safety profile of these closely related vectors is good. The gene therapy used in this trial has been tested for safety and effectiveness in animals. The EVERREST Clinical trial plans to administer the treatment directly to the mother’s uterine arteries, using minimally-invasive X-ray guided techniques. The trial will then follow-up all the participants and their babies closely for 5 years, looking at the health of the mother and health and development of their baby to assess the immediate and long-term safety of the therapy for this condition. For more information about the proposed EVERREST Clinical Trial please contact everresttrial@ucl.ac.uk.