U.K. COVID challenge study could streamline countermeasure trials
First COVID challenge trial to establish protocol for infection, set stage for faster testing of vaccines
First COVID challenge trial to establish protocol for infection, set stage for faster testing of vaccines and therapeutics.
Data from the first COVID-19 human challenge study could streamline future clinical trials of vaccines and treatments by reducing or better defining study populations.
Challenge trials that intentionally infect volunteers with SARS-CoV-2 promise efficiency in a pandemic that has routinely killed over a thousand people a day. The trials have not crossed from theory to practice, however, due to the risk that comes with the design.
Open Orphan plc (LSE:ORPH) is proceeding cautiously. The company said Wednesday that a Research Ethics Committee (REC) in the U.K. had approved the start of its COVID characterization study, initially described in October.
The trial, intended to be the first in a series of challenge trials, will not test any vaccines or therapies. It seeks to characterize infection with small amounts of virus in young healthy volunteers. The goal is to establish a challenge protocol, gain a deeper understanding of the immune response to the virus and explore why some people succumb to infection and others don’t.
Open Orphan’s hVIVO plc subsidiary will run the trial with Imperial College London and the Royal Free London NHS Foundation Trust; the U.K. government has agreed to contribute £33.6 million ($46.7 million).
hVIVO CSO Andrew Catchpole told BioCentury the study will determine the minimum amount of SARS-CoV-2 needed to cause reproducible infection, defined as PCR-positive nasal or throat swabs in 50-70% of individuals.
The trial will enroll up to 90 healthy, virus-naïve volunteers aged 18-30 and challenge them with a viral isolate with the D614G spike mutation that’s been circulating since March 2020 rather than emerging variants of concern, such as the B.1.1.7 variant first identified in the U.K. Because less information is available for SARS-CoV-2 variants, Catchpole said using the older isolate minimizes risk to study subjects and “will enable us to quickly switch to a variant virus in the future, as and when required.”
The information gained from the study could be used to design challenge studies comparing authorized vaccines to next-generation versions against select variants. The challenge format would enable those studies to be smaller and read out more quickly than the pivotal trials of the first tranche of COVID-19 vaccines, which enrolled tens of thousands of volunteers and required waiting for a sufficient number of them to be exposed to the virus in their environment.
In the first study, hVIVO will conduct virologic analyses, characterize T and B cell responses to infection, and use molecular techniques to probe SARS-CoV-2 and host cells changes. The study will follow participants for up to one year, potentially generating information about Long COVID-19.
The results could improve knowledge about why disease symptoms and severity vary across individuals, enabling drug developers to better identify which patients are likely to benefit from certain types of treatments. That should help guide enrollment in therapeutics trials.
The challenge trial will also provide information about asymptomatic COVID-19, which Catchpole expects most subjects to develop. Asymptomatic infection is “near impossible to study otherwise,” he added.