It has been announced that the UK will be the first country in the world to run a COVID-19 human challenge study, following approval from the UK’s clinical trials ethics body.
This Roundup accompanied an SMC Briefing.
Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said:
“The value of human challenge studies can be considerable, and the investigators here have a world class track record in this area. The proposed study will seek to define the minimal infectious dose for SARS-CoV2 in younger individuals, and will then apply this to vaccination trials, investigating, for example, the intervals between first and second doses.
“The study has received ethical approval from a dedicated research ethics committee, convened by the HRA; it was not deemed by the MHRA to be within remit, perhaps as this stage of the work there is no experimental treatment involved. The protocol contains an exhaustive list of criteria by which volunteers will be included, set out to minimise the risk of serious disease and death in participants.
“It’s encouraging to hear that, in the dose-finding initial part of the study, Remdesivir will be given at the earliest possible opportunity as soon as infection is confirmed. Nevertheless, it should be noted that this trial uses a more virulent agent compared to many that have gone before. It is very unlikely any of these young and healthy participants would go on to become very sick, and while we do know of treatments such as dexamethasone and tocilizumab help some patients with severe disease, we do not have a treatment that guarantees recovery in everyone so there does remain some small level of risk. Whilst we understand a great deal about the risk factors associated with severe COVID-19, it is not always clear why certain patients progress whilst others do not. It is also notable that even mild infection with SARS-CoV2 can cause longer term morbidity in a proportion of patients across all age groups, even following relatively mild infection.
“The non-natural, low dose infections generated will also need careful interpretation in order to relate the outcomes of the study to real-world disease, which is of course sadly present in abundance. However, one advantage of this study is that infections can be assessed right from their very initial stages to the eventual outcome.”
Prof Lawrence Young, Virologist and Professor of Molecular Oncology, University of Warwick, said:
“Human challenge trials in which volunteers are deliberately exposed to a pathogen have a long history. They have been used to study infections, treatments and vaccines to many different organisms ranging from the common cold viruses to malaria. Such controlled studies provide insights into the host-pathogen interaction, facilitate the identification of correlates of protection and accelerate the development of vaccines and novel therapies. This study will allow us to understand more about the dose of SARS-CoV-2 virus needed to infect an individual and to analyse the immune response under controlled conditions. It will also help us to better determine the activity of various vaccine candidates and to possibly investigate differences in response to infection with virus variants. Such controlled human infection studies need to demonstrate sufficient social value to justify the trial, have an acceptable risk-benefit profile and operate robust informed consent.”
Dr Charlie Weller, Head of Vaccines at Wellcome, said:
“Human infection studies have real potential to improve our understanding of Covid-19, which is crucial to the long-term pandemic response. These studies provide controlled, highly regulated environments that complement late-stage vaccine development by testing the effectiveness of current and new vaccines.
“Ethics Committee approval for this research is a very encouraging and important step. This type of study will boost Covid-19 vaccine research by providing vital insights such as how our immune system mounts a response to infection and how long immunity may last for.
“As with any human infection study, there are clear ethical considerations. The safety of volunteers is paramount and the ethical approval will have been through the highest level of assessment which includes review by the UK regulatory authority. Given that current treatment options for Covid-19 are limited, it is important that volunteers are being recruited from the lowest-risk groups and are closely monitored throughout the course of the study.
“Not only can human infection studies speed up vaccine development, but data from this study will provide key insights into how Covid-19 affects us from as soon as we are infected, which will potentially inform research into new treatments. Together, effective treatments, vaccines and testing will help communities around the world to protect themselves and bring this pandemic to an end.”
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Dr Stephen Griffin: “No declarations of interest.”
Dr Charlie Weller: “Wellcome is not a partner of this study but is a representative member of the UK Vaccines Taskforce, which is led by the Department of Business, Energy and Industrial Strategy.”
None others received.