LONDON – Human challenge specialist Open Orphan plc has raised £12 million (US$14.6 million) in a placing to accelerate development of COVID-19 challenge study models, to meet demand from vaccines and therapeutics developers worldwide.

In particular, the company is working on a challenge model based on an attenuated version of the SARS-CoV-2 virus, for use in vaccines testing.

Cathal Friel, executive chair, said the COVID-19 pandemic is generating unprecedented demand. “We believe the company has the pipeline to potentially sign up to six COVID-19-related challenge contracts in 2020, with a further six potential contracts in 2021,” Friel said.

The move to develop COVID-19 challenge models comes as clinical trials of therapeutics are seeing recruitment slow as the pandemic passes its initial peak. At the same time, vaccines developers are rushing to speed up field trials while the virus is still circulating.

Dublin-based Open Orphan’s viral contract research organization, Hvivo, has an existing portfolio of eight commercial viral challenge study models. It also has Europe’s only quarantine clinic, a 24-bedroom facility with linked virology lab in London, where it previously has run a variety of challenge studies of vaccines and antiviral drugs, in infections including influenza and respiratory syncytial virus.

An attenuated SARS-CoV-2 challenge model “would show a vaccine works, but at the same time, volunteers won’t have the nasties if it doesn’t,” Friel told BioWorld.

Hvivo has extensive experience in designing, validating and manufacturing challenge agents, and Friel estimates it will take six months to develop an attenuated strain of SARS-CoV-2. In parallel, Hvivo is working on the development of a coronavirus challenge model using the relatively harmless coronavirus strains OC43 and 229E, two viruses responsible for the common cold.

In March, the company began inoculating volunteers with those strains, which it says are an effective tool to obtain fast proof-of-concept data against members of the coronavirus family, allowing selection of the best candidates and fast-tracking for subsequent field testing.

Friel said Hvivo also is looking at the possibility of developing a wild-type SARS-CoV-2 challenge model. “But that would only be when there is much better rescue remedy,” he said.

Earlier this month, the World Health Organization released guidelines for assessing the ethical acceptability of human challenge trials in COVID-19, saying such trials would allow for more rapid and standardized testing.

The EMA agreed that challenge trials would be very helpful in various parts of the vaccines development process and would provide useful information to speed up regulatory approvals.

Attention has turned to the acceptability of human challenge trials because of concerns that SARS-CoV-2 transmission rates will fall to levels where it is not possible to complete field trials.

That has already come to pass in trials of therapeutics against COVID-19 infections, according to Peter Horby, professor of emerging infectious diseases and global health at Oxford University, who has been involved in carrying out clinical trials in epidemics including MERS, SARS-CoV-1 and the 2009 flu pandemic.

“We set up in Wuhan [China] in January and had the first trial running 19 days after [the emergence] of COVID-19 was announced by the CDC [Chinese Center for Disease Control and Prevention] and WHO, and we didn’t end up with sufficient data,” Horby said. “You’ve got to do trials in an epidemic – it’s not a luxury, it’s a must. You will only move forward if you have the evidence.”

Horby is principal investigator for the U.K.’s Recovery trial, which is testing existing therapies on hospitalized COVID-19 patients. The trial has recruited more than 10,000 patients, but the number of patients enrolling has gone down from a peak of 400 a day to 100 a day. That is still a large number, and Horby said the trial will complete, but the lower the recruitment rate means it will take longer to do so.

Racing to get the data

In the rush to get evidence before transmission slows, Oxford University’s vaccines group announced on May 22 that it has opened up the phase II/III trial of its AZD-1222 vaccine in advance of getting results from the 1,000 people who volunteered to take part in the phase I/II.

In total, the phase II/III will enroll 10,260 people. That will include people over the age of 56 and children ages 5 to 12, to see if there is variation in how well the immune system responds in older people and children.

The phase III part of the study will assess how the vaccine, which is licensed to Astrazeneca plc, works in a large population ages 18 and older.

The researchers say if transmission remains high they may get enough data in a couple of months to see if the vaccine works, but if the number of infections continues to go down, it could take six months.

The phase III trial is prioritizing recruitment of people with a higher chance of being exposed to SARS-CoV-2, such as health care staff and public-facing key workers, in an effort to capture efficacy data as quickly as possible.

One site opening at Glasgow University will recruit 250 front-line staff in intensive care units, emergency rooms and the ambulance service, including nonclinical staff such as porters and cleaners.

Meanwhile, the first COVID-19 vaccine to reach phase I has been found to be safe, well-tolerated and able to generate an immune response against SARS-CoV-2 in humans, according to research published in The Lancet. The open-label trial of the adenovirus type 5 vectored COVID-19 (Ad5-nCoV) vaccine in 108 healthy adults showed promising results after 28 days, with the final results due in six months.

“These results represent an important milestone,” said Wei Chen, professor at the Beijing Institute of Biotechnology in Beijing, China, who led the study. “The trial demonstrates that a single dose of the new vaccine produces virus-specific antibodies and T cells in 14 days, making it a potential candidate for further investigation.”

The Ad5-vectored COVID-19 vaccine uses an adenoviral vector to deliver genetic material that codes for the SARS-CoV-2 spike protein to host cells.

A randomized, double-blinded, placebo-controlled phase II trial of the vaccine has now started in Wuhan, in 500 healthy adults. That will include participants over the age of 60, an important target population for the vaccine.

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