Tuesday, October 20, 2020

UK Approves Human COVID-19 Vaccine Challenge Studies



Under normal circumstances it can take years to assess the effectiveness of a new vaccine, as thousands of volunteers much be vaccinated and then followed for months or even years to see if they are (statistically) less likely to be infected than unvaccinated members of the community. 

With a pandemic raging, and hopes pinned on a having vaccine in months rather than years, many researchers have suggested human challenge studies - where vaccinated volunteers are deliberately exposed to a virus in a controlled laboratory environment - rather than waiting for natural exposures to occur.

While this could shave months off of the regular testing schedule, it does entail some risks to the volunteers, and raises ethical issues as well (see Public Health Ethics Ethical Criteria for Human Challenge Studies in Infectious Diseases).  

Overnight the UK government, Imperial College London, and the Royal Free London NHS Foundation Trust have announced plans to begin a controlled human challenge study on COVID-19 vaccines starting in January. 

Excerpts and links to a couple of announcements. First, from the UK government:
Press release
Expert partnership to explore and establish Human Challenge studies of COVID-19 in the UK
£33.6 million government investment will back the studies in partnership with Imperial College London, hVIVO and the Royal Free London NHS Foundation Trust.
Published 20 October 2020
  • New research will explore the potential for new studies to accelerate development of a COVID-19 (coronavirus) vaccine
  • £33.6 million government investment will back the studies in partnership with Imperial College London, hVIVO and the Royal Free London NHS Foundation Trust 
  • a further £19.7 million will scale up capabilities to process blood samples from clinical trials
Experts from the NHS, academia and the private sector are today (20 October) joining forces with the government to explore and establish human challenge trials in the UK to speed up the development of a COVID-19 vaccine.
In human challenge studies, a vaccine candidate that has proven to be safe in initial trials is given to a small number of carefully selected healthy adult volunteers who are then exposed to the virus in a safe and controlled environment. Medics and scientists then closely monitor the effect on volunteers 24 hours per day to see exactly how the vaccine works and to identify any side effects.

As with all clinical studies in the UK, the proposed research will be carefully considered by regulators including the Medicines and Healthcare products Regulatory Agency (MHRA) and the NHS Health Research Authority through research ethics committees before any research starts.

Using controlled doses of virus, the aim of the research team  will initially be to discover the smallest amount of virus it takes to cause COVID-19 infection in small groups of healthy young people, aged between 18 and 30, who are at the lowest risk of harm. Up to 90 volunteers, who are compensated for the time they spend in the study, could be involved at this stage.

Human challenge studies offer the chance to accelerate development of promising vaccines against COVID-19, bringing them to people more quickly – potentially saving thousands of lives.

The studies are conducted under strict conditions – these include a controlled entrance to the facility, careful decontamination of waste and a dedicated laboratory for carrying out tests, all of which help to ensure the study is delivered safely and securely. All the air leaving the unit is also cleaned so there is no risk to anyone outside the unit.

Over many decades, human challenge studies have been performed safely and have played important roles in accelerating the development of treatments for diseases including malaria, typhoid, cholera, norovirus and flu. The trials have also helped researchers establish which possible vaccine is most likely to succeed in phase 3 clinical trials that would follow, usually involving thousands of volunteers.

If approved by regulators and the ethics committee, the studies would start in January with results expected by May 2021.

          (Continue . . . )

Our next press release comes from Imperial College London, which explains some of the rationales behind opting for controlled human challenge studies. 

UK researchers to explore human challenge studies for COVID-19

by Ryan O'Hare 20 October 2020

Researchers are set to explore a human challenge study with the virus that causes COVID-19, the first such study anywhere in the world.

The Human Challenge Programme is a partnership between Imperial College London, the Department for Business, Energy and Industrial Strategy (BEIS), hVIVO, a leading clinical company with expertise in viral human challenge models, and the Royal Free London NHS Foundation Trust.

The researchers hope that the work will ultimately help to reduce the spread of the coronavirus, mitigate its impact and reduce deaths from COVID-19.

The first stage of the project will explore the feasibility of exposing healthy volunteers to the SARS-CoV-2 coronavirus. The study would recruit volunteers between the ages of 18 and 30 with no previous history or symptoms of COVID-19, no underlying health conditions and no known adverse risk factors for COVID-19, such as heart disease, diabetes or obesity.

In this initial phase, the aim will be to discover the smallest amount of virus it takes to cause a person to develop COVID-19. This is known as a virus characterisation study.

Once this first phase is completed, clinical researchers aim to use this human challenge model to study how vaccines work in the body to stop or prevent COVID-19, to look at potential treatments and study the immune response.

Human challenge studies help clinical researchers establish which vaccines are most likely to succeed. As the prevalence of COVID-19 rises and falls in populations, it can make it difficult for traditional vaccine trials to assess if vaccines work, because volunteers receiving the vaccine may not be naturally exposed to the virus. Because a human challenge study deliberately infects the volunteers it should be possible for scientists to begin to establish efficacy very quickly, by testing if those who have had a vaccine are less likely to become infected with the virus.

Human challenge studies also make it possible for scientists to compare the efficacy of vaccine candidates by testing them side by side to establish which is more effective. At this early stage no specific vaccine candidates for the human challenge trials have been confirmed.

(Continue . . . )

Our last stop is a link to a Nature News report, which addresses some of the ethical concerns over these types of human challenge studies.

20 OCTOBER 2020

Dozens to be deliberately infected with coronavirus in UK ‘human challenge’ trials
Proponents of the trials say they can be run safely and help to identify effective vaccines, but others have questioned their value.

While the safety of a new vaccine is always the highest priority, its effectiveness in preventing infection or severe disease comes in a close second. 

And as we've seen recently with a number of failed therapeutics for COVID-19 (see WHO Solidarity Therapeutics Trial: Remdesivir, HCQ, Lopinar/Ritonavir & Interferon Disappoint), we can use them for a long time before we are able to determine if they are beneficial or not. 

With an increasingly vaccine-skeptical public, having some solid data on how protective a COVID-19 vaccine is might go a long way in increasing its uptake and acceptance.  

Of course, this initial study cohort will be young, healthy adults, and that may not tell us much about the vaccine's immune response in older, more vulnerable individuals or about the duration of protection from the vaccine.  

While I remain hopeful a safe and effective SARS-COV-2 vaccine can eventually be developed and deployed, there are still a lot of hurdles to overcome. Government and industry reassurances about the general availability of a vaccine by the spring are based on `best case' scenarios, and are best taken with a large grain of salt.