The University of Edinburgh and Cancer Research UK to conduct a trial to test use of potential virus-blocking treatment in improving COVID-19 outcomes
SPIKE-1 Trial; A Randomised Phase II/III trial in a community setting, assessing use of camostat in reducing the clinical progression of COVID-19 by blocking SARS-CoV-2 Spike protein-initiated membrane fusion
- The University of Edinburgh
- Cancer Research UK (Trial sponsor)
- Latus Therapeutics Ltd
- Professor Kev Dhaliwal, University of Edinburgh
- Prof Bruce Guthrie, The University of Edinburgh
- Prof Brian McKinstry, The University of Edinburgh
- Prof John Norrie, The University of Edinburgh
- Prof Daniel Anthony, University of Oxford
- Prof Grant Churchill, University of Oxford
- Dr Bobojon Nazarov, University of Oxford & Latus Therapeutics
- Dr Colin Ferrett, Oxford University Hospitals NHSFT
- Dr Suzie Anthony, Oxford University Hospitals NHSFT
- Dr Emma Ladds, University of Oxford, Primary Care
Latus Therapeutics is leading a joint research team of scientists from University of Oxford and the University of Edinburgh to commence a clinical trial testing camostat in early COVID-19 disease in 390 patients in the community setting. The trial is managed by Cancer Research UK with funding from LifeArc. Camostat is a drug widely used in Japan to treat pancreatic diseases. It is a serine protease inhibitor that also inhibits the TPMRSS2 enzyme which plays an important role in enabling SARS-CoV-2 to infect healthy cells. Although not yet tested in humans with COVID-19, studies in SARS infected mice have shown that camostat treatment can prevent death.
Potential of repurposed therapeutic for COVID-19 pandemic
Infection with SARS-CoV-2 (the virus responsible for COVID-19 disease) causes damage to cells and organs throughout the body. One potential treatment strategy for COVID-19 could be to block the virus from entering cells in the first place, thereby preventing cell damage and delaying replication of the virus within the body. Upon entering the body, the SARS-CoV-2 virus latches on to the ACE2 protein on the surface of cells lining the lungs, but the ability of the virus to enter cells is dependent upon another protein TMRPSS2.
Initial research has shown that inactivating the TPMRSS2 protein can stop virus entry into cells and prevent death following COVID-19 infection when tested in mice. Two drugs; camostat and nafamostat, which have been widely used in Japan to treat pancreatic disease and disseminated intravascular coagulation, have been shown to impair TPMRSS2-dependent entry of coronaviruses into cells and may help stop the disease in humans.
Latus Therapeutics with Cancer Research UK secured funding from LifeArc to conduct a Phase II/III multicentre prospective randomised study (SPIKE-1) that will explore the efficacy of camostat in COVID-19 outpatients compared against standard care (randomised 1:1 treatment and control arm). 195 patients will be included in each arm of the study, with patients in the treatment arm receiving orally administered camostat in tablet form at 200mg four times per day for fourteen days and those in the non-treatment arm receiving best supportive care. The primary outcome will be to evaluate the efficacy of camostat to prevent respiratory deterioration in patients with SARS-CoV-2 infection, with hospital admission requiring supplemental oxygen as the primary endpoint.
The trial will commence in Edinburgh and at multiple additional locations across the UK and is expected to be completed within one year of initiation.