Human Challenge Trial deliberately infects dozens of people in the UK

Young and healthy people are deliberately exposed to the virus that causes COVID-19 in the first “Human Challenge Trial” announced on October 20 by the British government and the company conducting such research. Will be done. The experiment, which is scheduled to begin in January at a hospital in London with final regulatory and ethical approval, aims to accelerate the development of vaccines that may end the pandemic. I will.

Human Challenge Trials have a history of providing insights into diseases such as malaria and the flu. The UK trial seeks to identify an appropriate dose of the virus SARS-CoV-2 that can be used in future vaccine trials. However, it is unknown medical and bioethical that even people at low risk of serious illness can be deliberately infected with SARS-CoV-2, a deadly pathogen with little proven cure. The area.

Proponents of the COVID-19 Challenge Trial argue that the potential for safe, ethical and rapid identification of effective vaccines outweighs the low risk of participants. However, others have questioned the safety and value of these studies, and large-scale efficacy trials in tens of thousands of people will soon yield results with some COVID-19 vaccines. It is pointed out that it is expected.

“The deliberate infection of volunteers with known human pathogens is never light, but such studies are very informative about the disease,” said an immunologist at Imperial College London. Researcher Peter Openshaw said in a press statement. “It is very important to act as quickly as possible to obtain effective vaccines and other treatments for COVID-19. Challenge studies accelerate the development of new drugs and vaccines and reduce risk. There is a possibility.”

Dose test

plan COVID-19 Challenge Study A Dublin-based commercial clinical research organization called OpenOrphan and its subsidiary, hVIVO, will conduct a challenging trial of respiratory pathogens. It takes place in a high-level isolation unit at the Royal Free Hospital in northern London, said Cathal Friel, an open orphan executive chair.

The UK Government’s COVID-19 Vaccine Task Force has agreed to pay the company up to £ 10m (US $ 13m) to conduct the trial. You may contract with OpenOrphan and do some more to test different vaccines. The UK Medicines and Healthcare products Regulatory Authority (MHRA) and the Ethics Review Board, which regulate clinical trials in the UK, must approve the initial trial and its design, as well as the design of future studies.

An estimated 30-50 participants will participate in the initial trial, said Andrew Catchpole, virologist and chief scientific officer of OpenOrphan, who is leading the work. Only available to healthy adults aged 18-30.

The exact design of the study has not yet been finalized. However, a small number of participants may receive a very low dose of SARS-CoV-2 “challenge strain” derived from the currently circulating virus and propagated under harsh conditions. If any or a few of the participants are infected, the researchers seek permission from an independent safety oversight committee to expose the participants to higher doses. This process is repeated until researchers identify the doses that infect most of the exposed people, says Catchpole.

Once the appropriate dose has been identified, Open Orphan may be asked to perform a series of challenging trials testing several vaccines. Catchpole states that the design of these trials, including which vaccines are included, has not been determined. He expects some study participants to receive placebo injections instead of vaccines, but he also states that direct trials can be conducted comparing two or more vaccines. Other vaccine studies conducted by the company typically enroll 40 to 50 volunteers in each study group, he says.

Catchpole states that his team will take all precautions against participants in the first trial to develop severe illness. If the nasal swab gives a positive result for the SARS-CoV-2 genetic material, volunteers are treated with antiviral drugs such as remdesivir. In addition to age and health, participants will be screened for risk factors associated with severe COVID-19.

Matt Memory, an infectious disease specialist and virologist at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, said choosing the lowest-risk participant was the key to conducting a challenge trial. It states that it is the most important safety step. “If you give that person the virus, you can do anything,” he says. “You can’t control it, you can only react to it.”

When Open Orphan moves to a vaccine trial, it aims to recruit a total of about 500 participants, but Friel needs to screen many times more to identify suitable volunteers. It states. The Ethics Review Board decides how to reward participants. Open orphans usually pay volunteers around £ 4,000 for their time, says Catchpole.

Ethical issues

Nir Eyal, a bioethicist at Rutgers University in New Brunswick, NJ, said there was concern that people would participate for money without being aware of the risks. Claimed that the COVID-19 Challenge Trial could be carried out safely and ethically.. But, for example, a well-designed online course can ensure that participants understand the risks, he says.

Seema Shah, a bioethicist at Lurie Children’s Hospital and Northwestern University in Chicago, Illinois, said it was also important for participants to understand the limitations of challenge trials. She believes that the challenge trial is unlikely to accelerate the development of the first vaccine, as many Phase III trials of the COVID-19 vaccine are underway. Instead, their reward may be to support the testing of vaccines in later generations, or to lay the groundwork for fresh insights into the disease. In this context, Shah says. “It gets a little harder to justify them, and we need to look carefully at the risks.”

Meagan Deming, a vaccine scientist and virologist at the University of Maryland School of Medicine in Baltimore, studies the basic aspects of SARS-CoV-2 infection, including potential reinfection and previous cold exposure. In addition, I think the challenge exam is more appropriate. Inducing coronavirus affects susceptibility to COVID-19 more than vaccine testing. How the vaccine can protect people at the highest risk of serious illness, such as the elderly and people with diabetes and other conditions, because such trials are likely to target only young and healthy people. It may not be very clear about this. “There’s a reason why there aren’t many vaccines approved in the challenge model, because they don’t apply to everyone, they need a vaccine that protects almost everyone,” she says. I will.

Peter Smith, an epidemiologist at the London School of Economics and Tropical Medicine and participating in a challenge trial, said Phase III trials may not provide clear evidence of whether the vaccine works for older people. It states that there is. Researchers will need to determine the effectiveness of the vaccine in the elderly based on how the immune system responds to the COVID-19 vaccine before it is exposed to the virus. Compared to field trials, challenge studies are better at identifying the type of immune response that predicts whether a vaccine may work, Memoli adds.

Other exams

The UK is not the only country investigating the COVID-19 Challenge Trial. The Belgian government has pledged € 20 million (US $ 23.6 million) to a facility hosting a challenge trial that may involve COVID-19. NIAID is funding the development of two SARS-CoV-2 Challenge strains by a laboratory at Colorado State University in Fort Collins, and a team led by Memoli is also laying the foundation for such trials. In a statement, NIAID said it was waiting for data from the Phase III trial before making a decision on the COVID-19 Challenge trial.

Proponents of the trial argue that the consequences of delaying the trial should be considered along with future risks. For example, London’s Imperial College Eyal and economists Pedro Rosa Diaz and Ara Darzi have reduced the development of the COVID-19 vaccine by one month to avoid a loss of 720,000 years of life and prevent 40 million years of poverty. I’m calculating that I can. Low-income country.

However, Deming believes that challenge trials need to wait until their value becomes clear and the risk can be further mitigated, for example by developing more powerful therapies. “We still don’t know enough about this illness to say for this person: you won’t die,” she says. “I’ve learned a lot in the last nine months. Within a year, I’ll be able to do this safely.”

This article has been reproduced with permission First edition October 20, 2020.