UK Government Plans Human COVID-19 Challenge Trials with CRO
There has been some discussion of running challenge trials for COVID-19 vaccines. In a challenge trial, people are given a vaccine and then intentionally dosed with the virus or bacteria that causes the disease. For diseases that are very deadly without reliable therapies, it is considered unethical and very dangerous.
But the UK is going to go ahead and try it anyway. The UK government’s COVID-19 Vaccine Taskforce and a contract research company called Open Orphan announced a $13 million (£10 million) plan to test investigational COVID-19 vaccines in volunteers who are then intentionally exposed to SARS-CoV-2, the virus that causes COVID-19. The trials won’t begin until early 2021 and are expected to finish in May 2021. They will require regulatory and ethical approval.
Open Orphan announced that its subsidiary, hVIVO, signed a contract with the UK Government to develop the human challenge study model. It will involve manufacturing the challenge virus and the “first-in-human characterization study for this virus.”
The UK government has reserved “the first three slots to test vaccines using hVIVO’s COVID-19 challenge study,” and each has been secured at a cost of £2.5 million each, which brings the total value of the slot reservations to £7.5 million.
The study will be sponsored by Imperial College London and run by hVIVO at The Royal Free Hospital’s specialist research unit in London. hVIVO also plans to expand its Clinical Operations in London to handle work at the site. hVIVO has a state-of-the-art, category 2 facility at Queen Mary’s Bioenterprise Centre in London, and plans to continue using it to deliver its traditional challenge study contracts, especially in respiratory syncytial virus (RSV), and is booked to maximum capacity until Summer 2021.
“At Open Orphan we are pleased to be working on behalf of the UK Government and in partnership with two great institutions, Imperial College London and The Royal Free Hospital,” said Cathal Friel, executive chairman of Open Orphan. “We look forward to working with our partners to develop a COVID-19 human challenge study model which will be used to safely accelerate the discovery of effective vaccines and antivirals against COVID-19.”
People for challenge trials argue that they can be conducted both safely and ethically with the potential to speed vaccine development outweighing the risk to the participants. The counterargument is that large-scale clinical trials are already ongoing involving tens of thousands of volunteers and will likely have results by the end of the year.
In fact, Pfizer and BioNTech are expected to file for emergency use authorization with the U.S. Food and Drug Administration (FDA) and potentially the European Medicines Agency (EMA) by the end of November, and it is likely Moderna will be filing with the FDA before the end of the year, with potentially AstraZeneca and the University of Oxford doing so as well. The next likely candidate to file is Johnson & Johnson, although they appear to be several months behind the leaders. There are, of course, no guarantees that they will all prove to be safe and effective enough, although early data is promising.
“Deliberately infecting volunteers with a known human pathogen is never undertaken lightly,” said Peter Openshaw, an immunologist with Imperial College London and an investigator in the study. “However, such studies are enormously informative about a disease. 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.”
Andrew Catchpole, a virologist and chief scientific officer at Open Orphan, who is leading the work, indicated the initial trial will probable involve 30 to 50 volunteers, all healthy adults aged 18 to 30. They will receive a very lose dose of a SARS-CoV-2 “challenge strain” derived from the currently circulating virus and grown under strict conditions. If none of the volunteers become infected, the investigators will request permission from an independent safety monitoring board to expose volunteers to higher doses. Catchpole indicates they will repeat the process until they identify a dose that infects most of the volunteers.
Once that dose is identified, they may conduct a series of challenge trials evaluating several vaccines. The actual design and which vaccines has not been determined yet. Catchpole does believe some will receive a placebo instead of a vaccine, and there is also a possibility that head-to-head trials of two or more vaccines might be conducted.
He also indicates that volunteers, once a nasal swab results in a positive test, will receive an antiviral, such as Gilead Sciences’ remdesivir. Volunteers will also be screened for risk factors associated with severe disease.
If it gets to actual vaccine trials, Open Orphan will plan to recruit about 500 participants altogether. An ethical review board will decide how they are to be compensated. Typically, Open Orphan pays volunteers about £4,000, or about $5,169 (U.S.).