The UK government has signed a contract for the first human challenge studies for the novel coronavirus, in which healthy volunteers are deliberately infected with the virus in a controlled setting, and some receive an experimental vaccine.
Up to 19 volunteers at a time will take part in the tests, to be held at the Royal Free Hospital in London, which houses a Biosafety Level 3 ward. They will be run by hVIVO, a medical research company that specializes in running challenge trials, in partnership with Imperial College London.
These clinical trials will be a little different from most.
For the current Covid-19 vaccine candidates that are in Phase 3 – the final stage of testing – tens of thousands of volunteers are given an experimental vaccine and then released to live their everyday lives; researchers assume that a certain percentage of them will be exposed to the virus naturally.
In a challenge trial, by contrast, participants are deliberately dosed with virus.
Proponents of challenge trials say that they are more efficient, requiring far fewer volunteers – likely in the hundreds – because researchers know for certain that everyone will be exposed to the virus, and that they can deliver scientific data more quickly.
Critics worry about exposing people to a virus for which there is no fail-safe treatment, and say that the young, healthy volunteers are not representative of the wider population.
“We are doing everything we can to fight coronavirus, including backing our best and brightest scientists and researchers in their hunt for a safe and effective vaccine,” said Alok Sharma, the UK’s Business Secretary.
“The funding announced today for these ground-breaking but carefully controlled studies marks an important next step in building on our understanding of the virus and accelerating the development of our most promising vaccines which will ultimately help in beginning our return to normal life.”
As a first step, hVIVO, a subsidiary of the Irish company Open Orphan, will conduct a characterization study at the beginning of 2021. That involves deliberately exposing a small number of healthy volunteers to the coronavirus, to determine the minimum dose that leads to symptomatic infection.
“We want to find out right from the word go how the human body reacts to a dose of the virus,” Dr. Martin Johnson, Senior Medical Director at hVIVO, told CNN.
The company plans to be able to test the efficacy of up to three vaccine candidates sometime next year.
A September article in the New England Journal of Medicine argued that challenge trials could “accelerate development of later rounds of vaccine candidates,” as well as help researchers better see how the virus attacks the human body.
Several potential vaccines are already nearing the end of traditional phase 3 trials using “natural” exposure to the virus, but simply showing that as vaccine has some effectiveness in preventing the onset of Covid-19 does not mean it is the best that scientists can do.
The characterization study, and vaccine trials, will still need ethics approval from UK regulators. England’s Health Research Authority tells CNN that it has already set up an ethics committee to assess any challenge trial proposals.
Volunteers will be rigorously screened to ensure they are in good health, with no pre-existing conditions. They will need to be between the ages of 18 and 30, hVIVO says. They will be compensated for their participation, but regulators will want to ensure that the amount does not appear coercive.
Volunteers will remain in residence at the Royal Free Hospital for the duration of the trial, which could last several weeks. hVIVO has isolated a strain of the virus taken from a British Covid-19 patient, and will expose the volunteers to the virus through the nose, using a pipette.
“We are actually going to take the very smallest dose,” Dr. Johnson said. “What we’re trying to do is we’re trying to get the minimum number of symptoms that are safe.”
As soon as a patient has displayed symptoms of Covid-19, he said, doctors will administer the antiviral remdesivir. Scientists at hVIVO point out that unlike coronavirus patients who are admitted to the hospital, challenge trial volunteers will be treated at the first sign of infection.
However, there are no treatments shown to help patients early on in the course of the virus.
Once the characterization study is complete, hVIVO will ready itself for testing up to three vaccine candidates, as determined by the UK’s government-led Vaccine Taskforce.
Those candidates could be vaccines that are not yet in Phase 3 trials, or field-tested vaccines for which scientists want more data, Dr. Johnson said.
Challenge trials are nothing new, and have been carried out for cholera, typhoid, malaria, and even influenza. But unlike for those diseases, we do not yet have a completely effective treatment for Covid-19, should the experimental vaccine fail.
Dr. Johnson said a challenge study for coronavirus is only possible now because of the promising performance of treatments like remdesivir and the steroid dexamethasone.
The World Health Organization recently found that remdesivir doesn’t appear to save Covid-19 patients’ lives, or help them recover faster, and there is no data to suggest it helps patients early in the infection. The current guidance is that dexamethasone should not be given to patients unless they are severely ill.
“The problem is, when you are doing trials out there in the in the wild, you don’t know exactly when a patient has been infected. Here, we know to the second when they’ve actually received the virus. So we can look at it and track it all the way through,” Johnson said.
The announcement comes just as tens of thousands of people around the world have expressed their interest in volunteering for a coronavirus human challenge study through the organization 1 Day Sooner. hVivo says it is talking to 1 Day Sooner about identifying potential volunteers.
One of the UK organizers for 1 Day Sooner, 18-year-old Alastair Fraser-Urquhart, told Phil Black earlier this month that challenge studies are “just such an instant, common sense idea.”
“The risk to me is tiny. But by taking that small risk on myself, I can potentially protect thousands of other people from having to be infected without consenting to it.”