If approved by regulators and ethics committees, the UK's human challenge trials will be the first in the world for coronavirus.
The UK Government has today announced a cross government, academia and private sector partnership 'to explore and establish' human challenge trials for COVID-19. This involves Imperial College London, clinical company hVIVO and the Royal Free London NHS (National Health Service) Foundation Trust: and is backed by a $43m government investment.
The human challenge trials are eyeing a January start date, with the first results expected in May.
In human challenge studies, consenting healthy volunteers are exposed to the virus in a controlled environment. The aim of the UK challenge studies will be twofold: firstly to ascertain the level of virus that causes an infection; and secondly to assess the efficacy of vaccine candidates.
Two part project
The first stage of the project will be carried out by Imperial College London, the Royal Free Hospital’s specialist and secure research unit in London, and clinical company hVIVO.
Backed by a £33.6m ($43m) government pot, the virus characterisation study will hope to determine the smallest amount of virus it takes for a person to develop a COVID-19 infection.
The study will involve up to 90 healthy young people, aged 18 to 30, who are considered to be at the lowest risk of harm from the virus. The challenge trials will take place in facility at the Royal Free which has been specifically designed to contain the virus. Medics and scientists will examine how the virus behaves in the body and ensure volunteer safety.
Volunteers – who will be compensated for the time they spend in the study - will be monitored for up to a year after participating in the study to ensure their long-term well-being.
Once this first phase is completed, researchers will deploy this human challenge model to study how vaccines work in the body to stop COVID-19.
The project has not yet determined which vaccine candidates will be assessed. However, it notes that human challenge trials could be used to pick out the most promising vaccines in the mid-stage of development to take forward to larger Phase 3 trials; while they could also be used for vaccines that are already in Phase 3 trials to further understand if they can prevent transmission as well as preventing illness.
Professor Peter Openshaw, co-investigator on the study and Director of the Human Challenge Consortium at Imperial College London, said: “Deliberately infecting volunteers with a known human pathogen is never undertaken lightly. However, such studies are enormously informative about a disease, even one so well studied as COVID-19.
“It is really vital that we move as fast as possible towards getting effective vaccines and other treatments for COVID-19, and challenge studies have the potential to accelerate and de-risk the development of novel drugs and vaccines.”
Human challenge trials: regulatory and ethical considerations
Human challenge studies have been carried out over the last few decades in other disease areas such as typhoid, cholera and influenza.
A standard clinical trial sees volunteers vaccinated to see if they develop a disease circulating in the community over several months. In human challenge studies, a smaller group of volunteers is deliberately exposed to an infection after they have been vaccinated.
As well as regulatory approval, human challenge trials must obtain the green light from ethics boards.
In May, the WHO set out the key criteria for the ethical acceptability of COVID-19 human challenge studies. It noted that such studies can be particularly valuable for testing vaccines: because they can be substantially faster to conduct than vaccine field trials (partly because fewer participants need to be exposed to experimental vaccines in order to provide preliminary estimates of efficacy and safety).
Such studies can also be used to compare the efficacy of multiple vaccine candidates and thus select the most promising vaccines for larger studies. “Well designed challenge studies might thus not only accelerate COVID-19 vaccine development, but also make it more likely that the vaccines ultimately deployed are more effective,” says the WHO in its criteria.
It notes that human challenge trials ‘may seem intuitively unethical’; but concludes that “there is a consensus among ethicists who have reflected upon human challenge studies that the intentional infection of research participants can be ethically acceptable under certain conditions, such as those in which modern challenge studies are conducted.”
Human challenge trials have to prove to regulators and ethical committees that the potential benefits of a trial outweighs the risks; that they can be conducted at the highest scientific, clinical and ethical standards; and that participant selection criteria limits and minimizes risk. In the UK, this will be the Medicines and Healthcare products Regulatory Agency (MHRA) and the NHS Health Research Authority.
hVIVO: developing the human challenge study model
hVIVO, a subsidiary of CRO pharmaceutical services company Open Orphan, has signed a contract with the UK Government to develop the COVID-19 (SARS-CoV-2) human challenge study model.
This involves the manufacture of the challenge virus and the first-in-human characterisation study for this virus. The contract starts immediately and could be worth around £10m ($13m) to hVIVO depending on the number of volunteers in the characterisation study.
In addition, the Government has secured the first three slots to test vaccines using hVIVO's COVID-19 challenge study, with each slot reservation secured at a cost of £2.5m / $3.2m (totalling £7.5m/ $9.7m).
The study will be sponsored by Imperial College London and conducted by hVIVO at The Royal Free Hospital's specialist research unit in London. hVIVOwill also expand its Clinical Operations in London to facilitate work at this site.
hVIVO – formerly known as Retroscreen Virology – was established in 1989 as a spin out from Queen Mary University, London. The company has the world's leading portfolio of eight human challenge study models developed to date and says it has safely run more human challenge studies than any other company globally.
hVIVO's category 2 facility at Queen Mary's Bioenterprise Centre, London, will continue to be used to deliver the company's existing challenge study contracts, such as respiratory syncytial virus (RSV).