Major Trials Sponsored by UK Government Target At-Risk Immunocompromised Patients & Elderly in Nursing Homes

Major Trials Sponsored by UK Government Target At-Risk Immunocompromised Patients & Elderly in Nursing Homes

Recently, the United Kingdom (UK) government’s Department of Health and Social Care (DHSC) announced two clinical trials supported by up to £3.2 million ($4.4m) on what are considered “pioneering” treatments thought to possibly be able to stop the spread of SARS-CoV-2, the virus behind COVID-19. The targeted subject are the hundreds of thousands of clinically vulnerable people and home care residents. In one study called the PROTECT-V trial, the University of Cambridge will investigate drugs that may serve to prevent COVID-19 infection among immunocompromised groups while the second study, called PROTECT-CH, is led by the University of Nottingham and investigates treatments for reducing the transmission of COVID-19, as well as hopefully reduce the threat of serious illness for care home residents and staff. The trial sponsors acknowledge British scientists and taxpayers have already contributed to breakthrough studies showing the benefit of two drugs, including dexamethasone and tocilizumab, the later drug with mixed results, as many prominent studies demonstrate no benefit. The British government is on the record that the end of the pandemic will be introduced by not only vaccines but also the combination of testing and safe and effective therapeutics. Put another way, the vaccine will not always be sufficient, for example, with immunocompromised patients who may not mount as strong a response to the vaccine as healthy individuals will. In the PROTECT-V trial, a novel nasal-based anthelmintic drug (like ivermectin) that turns out to be a SARS-CoV-2 inhibitor developed in Denmark will be tested on at risk UK residents. The government controls what drugs will be included in the PROTECT-CH trial, and they are not sharing which as of yet.

When combining these two studies, government health authorities here in England believe up to half a million people might benefit from such treatments should they prove safe and effective. These two clinical trials are acknowledged as highly critical, given Urgent Public Health badging status from the apex research body in the UK called the National Institute for Health Research. Protect-V received £1.5 million for study expansion while Protect-V received £1.7 million in government funds.

From the national government, that is the National Institute for Health Research (NIHR), the study is co-ed by Professor Chris Whitty, Chief Medical Officer for England. Now these two important NIHR-funded clinical trials will evaluate prophylactic treatments for COVID-19 in care homes (e.g. nursing homes) and those at risk individuals with compromised immune systems.

Protect-V trial

Called the PROphylaxis for vulnerable paTiEnts at risk of COVID-19 infecTion (PROTECT-V) trial, this study was recently authorized to proceed by the UK Medicines and Healthcare products Regulatory Agency (or MHRA). It was launched just this month and will run for about a year. The study involves 2,250 immunocompromised participants. Led by University of Cambridge, the PROTECT-V trial is actually what is known as a platform designed to investigate drugs that may prevent COVID-19 infection in those considered more vulnerable, such a patients with kidney disease on dialysis for example reports the University of Cambridge’s Dr. Rona Smith, Senior Research Associate for PROTECT-V.

The Drug

For the PROTECT-V trial, the University of Cambridge has selected an investigational product that’s delivered in the form of a nasal spray delivering niclosamide, a potent inhibitor of SARS-CoV-2 with in-vitro potency greater than 40 times higher than remdesivir in the nasal cavity.  Called UNI91103, it will be trialed first now in the UK with about 1,500 kidney patients to assess if the drug can prevent patients from contracting symptomatic COVID-19 or reduce serious illness and death from infection. Although the drug hasn’t been tested in humans, it has been shown to prevent fatal outcomes in animal models of COVID-19 when administered intranasally.

The study is overall funded by LifeArc, Kidney Research UK, the Addenbrooke’s Charitable Trust, Union Therapeutics (the drug’s sponsor) with additional support of course from the NIHR Cambridge Biomedical Research Centre.

UNION Therapeutics A/S, a Hellerup, Denmark-based privately held biotech company, develops novel treatments for inflammatory and infectious diseases. The company is primarily working on two complementary chemistry classes across immunology and microbiology and has multiple candidates in clinical development.

PROTECT-CH Trial

This study has been planned to respond to the devastating impact of COVID-19 on the elderly residing in what are called care homes in the UK (in the U.S. long term care facilities or nursing homes). The pandemic has had a devasting impact on this cohort in places such as the UK, Canada and the USA.

Called Prophylactic Therapy in Care Homes Trial (PROTECT-CH), the trial starts in May and will run for two years involving more than 400 care homes (long-term care in the U.S.) including up to 12,000 elderly and at risk residents. This study is led by University of Nottingham and is organized to reduce transmission and lower the risk of serious illness for staff and home care residents.

This large platform trial will test several treatments intended to reduce the spread of the virus within care homes and reduce the risk of hospitalization and death. Like all platform trials, this enables the sponsor and investigators to test multiple treatments in parallel, with results regularly analyzed. Once a particular treatment exhibits positive efficacy, it can be added, ineffective ones removed.

While the University of Nottingham leads the study, other major academic research centers support the study, including the Universities of Cambridge, Edinburgh, Surrey and Warwick as well as University College London.

PROTECT-CH was recently introduced by Adam Gordon, Professor of Care of Older People and Co-Chief Investigator of the trial, via a series of webinars. These webinars aimed to help homecare staff learn more about what participating in the clinical trial involves, and how staff and residents can participate. See the link

They Don’t Know What Drugs

Interestingly, the PROTECT-CH cannot share which drugs will be included—in fact, they haven’t been selected as of yet. In an FAQ, the sponsors acknowledge, “At the moment, we don’t yet know which treatments will be tested. These will be chosen by the Government’s medical advisors. The study is designed to be able to test several treatments in parallel. As soon as a treatment is shown to be effective or ineffective, it is removed from the study. This makes space for new treatments to be tested in the study.”

Control in the Government Hands

Given the central government apex research body NIHR is primarily funding the study, they will be selecting what drugs they will use.

TrialSite Comment on Generics

We note that the Danish company UNION therapeutics uses an anthelmintic drug, which is the same class that ivermectin falls under. Given the numerous ivermectin studies in humans and the fact that this new Danish drug is novel and not tested in humans, wouldn’t it be rational to consider ivermectin in such a broad based public experiment? In both cases, a generic, repurposed economical drug with a safe profile that works could be compelling.

Call to Action: TrialSite will monitor this situation in the UK carefully.

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