From today, favipiravir will be investigated in the UK as part of the Platform Randomised trial of Interventions against COVID-19 In older peoPLE (PRINCIPLE), the world’s largest clinical trial of possible COVID-19 treatments for recovery at home and in other non-hospital settings.
Led by University of Oxford researchers, PRINCIPLE is one of the UK Government’s national priority platform trials for COVID-19 treatments and was set-up with the intention that drugs shown to have a clinical benefit could be rapidly introduced into routine NHS care.
Favipiravir is an antiviral drug which has been licenced in Japan since 2014 to treat influenza. It works by inhibiting a viral enzyme called RNA polymerase, preventing viral replication within human cells. This viral enzyme is common to several viruses, including SARS-CoV-2, which causes COVID-19.
The drug has shown positive results against SARS-CoV-2 in laboratory and animal studies, with small pilot studies in humans demonstrating some benefit in reducing symptoms and the duration of illness.
Launched in March 2020, PRINCIPLE has so far recruited more than 4,700 volunteers from across the UK. The trial is evaluating a range of potential community treatments for COVID-19 to reduce recovery time and prevent hospital admissions and deaths. It is recruiting participants who are most at risk of serious COVID-19 illness, either due to their age, symptoms, or an underlying health condition.
PRINCIPLE trial Co-lead Investigator, Chris Butler, a South Wales GP and Professor of Primary Care the University of Oxford’s Nuffield Department of Primary Care Health Sciences, said ‘Viruses need human cells to multiply and survive, and favipiravir blocks the complicated molecular dance that happens between a virus and our own cells when the virus is replicating.
‘Until now, we have been testing medicines that have not typically been used to treat viral infections. This is the first drug we will be testing that was designed specifically to target viruses, so we are particularly excited to be including favipiravir in the PRINCIPLE trial to determine whether it could be used in the community as a COVID-19 treatment and prevent people from getting very sick.’
PRINCIPLE trial Co-Investigator, Gail Hayward, an Oxfordshire GP and Associate Professor in the University of Oxford’s Nuffield Department of Primary Care Health Sciences, said: ‘Even with the successful vaccine rollout, it’s the combination of vaccines, testing and treatments that will bring an end to this pandemic. There still isn’t a safe and effective therapeutic for COVID-19 that we know for sure will prevent people needing to go into hospital for treatment. By joining the PRINCIPLE trial, people with coronavirus symptoms could play a vital role in helping to transform COVID-19 into an illness that can potentially be treated by your regular general practitioner.’
Following a screening questionnaire to confirm eligibility, participants enrolled in the study will be randomly assigned to receive an initial two doses of 1800mg favipiravir on day one, followed by 800mg twice a day for a further four days. They will be followed-up for 28 days and will be compared with participants who have been assigned to receive the usual standard of NHS care only. People aged 50 to 64 with certain underlying health conditions or shortness of breath from COVID-19, or aged over 65, are eligible to join the favipiravir arm of PRINCIPLE within the first 14 days of experiencing COVID-19 symptoms or receiving a positive test.
Participants can join from anywhere in the UK, either online, over the phone or via a healthcare professional, and without needing face-to-face visits with the trial team in Oxford.
Favipiravir is the sixth drug and the first antiviral to be evaluated by the PRINCIPLE trial. The decision to add favipiravir to the trial was made by the University of Oxford researchers and trial steering committee leading the trial in conjunction with the Chief Medical Officer for England, following a recommendation by the UK COVID-19 Therapeutics Advisory Panel.
Other treatments under investigation include budesonide, an inhaled steroid typically used for treating lung inflammation, and colchicine, an anti-inflammatory drug traditionally used for treating gout, which is being evaluated in adults aged over 18.
The trial has so far found that the antibiotics azithromycin and doxycycline are not generally effective as treatments during the early stages of COVID-19, with implications for how COVID-19 illness is treated both in the UK and internationally.
PRINCIPLE is funded by a grant to the University of Oxford from UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) as part of the UK Government’s rapid research response fund.
The trial is supported by the NIHR and a vast network of health and care professionals in care homes, pharmacies, NHS 111 Hubs, hospitals and more than 1000 GP practices across England, Wales, Scotland and Northern Ireland.
To find out more about how to join the study, visit www.principletrial.org