An Oxford-led clinical trial in West Africa will test out a novel antiviral drug against Ebola, in a three-pronged emergency effort also involving vaccination of healthy test subjects in Oxford and a mapping project to predict new outbreaks.
An Oxford-led clinical trial in West Africa will test out a novel antiviral drug against Ebola.
The trial of brincidofovir, involving an international team led by Oxford University scientists, will take place in an Ebola treatment centre run by Médecins Sans Frontières.
The trial of the experimental treatment comes alongside efforts to find an effective vaccine against the disease, with the 60th and last healthy volunteer in a trial carried out by Oxford receiving a candidate Ebola vaccine this week. At the same time, Oxford is involved in a mapping project to predict the likeliest hotspots for new Ebola cases in West Africa.
The brincidofovir trial, funded by the Wellcome Trust, will be carried out by an international team including the University of Oxford. It could start within weeks, pending approval by ethics committees in Oxford and West Africa, and at Médecins Sans Frontières and the World Health Organisation.
Professor Peter Horby of Oxford University and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), the chief investigator of the trial, said: ‘Conducting clinical trials of investigational drugs in the midst of a humanitarian crisis is a new experience for all of us, but we are determined not to fail the people of West Africa. It has been a privilege to witness the extraordinary willingness of all the partners in this initiative to step outside their comfort zones in order to fast track these critically important trials.’
Professor Trudie Lang of Oxford University, who is a member of the research team, said: ‘As the Ebola crisis deepens, the problem we have is that we do not know whether any of the drugs in development would work, or would be safe to use. Could any of them help in the current epidemic? We don’t know, but we need to find out as quickly as possible. The only way to determine that is through a clinical trial.
‘We are working in full partnership with international organisations and colleagues in West Africa to conduct a clinical trial to find out. Typically it takes over 18 months to set up a trial, and that is in a “normal” situation. Here we need to set up a trial within weeks.’
Brincidofovir, made by US pharmaceuticals firm Chimerix, works by interfering with a virus’s ability to replicate its genetic material. It is currently in advanced clinical trials for treating adenovirus and cytomegalovirus infections, which provide plenty of data on its safety profile. Test-tube studies have shown good activity against the Ebola virus.
There is good data on brincidofovir’s safety in humans from trials for other viral infections. It is easy to give: it is an oral drug, taken twice a week. And should it prove to be an effective treatment, its manufacture would be relatively easy to scale up.
In the trial — also involving Institut Pasteur, Institut Pasteur de Dakar, Fondation Mérieux and the Global Health Network — brincidofovir will be given to all patients in the treatment centre consenting to take part.
The two-week treatment course would involve up to 140 adults with Ebola disease, who would be monitored and have blood samples taken. Pregnant women are excluded, as the drug has shown some adverse effects on embryos in animal studies.
The main outcome measure would be fatality rate among the Ebola patients taking part. This would be compared against the previous death rate seen among patients in the treatment centre before the trial began.
The study could also make use of an adaptive trial design, where the design can be modified as the trial progresses and data builds up. The trial can be stopped early if the drug shows clear benefits or harm. It may also be possible to add other novel drugs into the trial as they reach a point where they can be tested, or to allow comparisons between candidate drugs.
Piero Olliaro, a visiting professor at the University of Oxford and a Senior Research Manager at the WHO-based Special Programme for Research and Training in Tropical Diseases, said: ‘This trial design is no short cut, no compromise on science or ethics. At the same time, a trial like this has never been done in a humanitarian disaster before. It needs innovative approaches for triaging patients and assessing their condition, all in difficult conditions in an emergency situation.
But he cautioned: ‘I strongly believe that no individual measure will solve the problem. We shouldn’t look to new vaccines or drugs as being the sole thing that will bring the Ebola epidemic under control. We need to look at the overall picture and work on all aspects: new vaccines and treatments, yes, but also containment measures and strengthening the support available on the ground.
The brincidofovir trial is one of three clinical trials of potential treatments for Ebola announced this week which will be carried out by European teams at Médecins Sans Frontières treatment centres in West Africa.
Principal investigators of the three trials are working closely together to ensure they are coordinated, complementary and comparable. Results will be shared widely as soon as they are available.
Meanwhile in the vaccination study, the number of healthy volunteers injected with a candidate vaccine in Oxford reached 60 this week.
The volunteer was one of 200 people who have now received the vaccine in little more than two months in safety trials carried out in the USA, UK, Mali and Switzerland.
‘The safety data here have looked very satisfactory so far,’ said Professor Adrian Hill of the Jenner Institute at Oxford University, who is leading the Oxford trial. ‘The response we have seen from people coming forward to take part has been remarkable.’
The candidate Ebola vaccine is being co-developed by the US National Institutes of Health and GlaxoSmithKline (GSK) using a single Ebola virus gene in a chimpanzee adenovirus to generate an immune response. As it does not contain infectious Ebola virus material, it cannot cause a person who is vaccinated to become infected with Ebola.
In the third prong of Oxford University activity to counter Ebola, research to predictively map the geographic spread of Ebola virus in West Africa has been funded by the British government and the Wellcome Trust.
Oxford scientists have developed maps showing where the Ebola virus is likely to be carried by animals and where transmission to humans may trigger future outbreaks. The new project will use data on human mobility, population density, and transport infrastructure in West African countries to create maps predicting how the current Ebola outbreak is likely to spread through human populations.
The project, led by Professor Simon Hay and Dr Nick Golding of Oxford’s Department of Zoology, will give indications of the risk of the virus spreading to neighbouring countries and will include summaries of health centres most likely to see new cases.
Both the maps and the online tools to create them will be made freely available to help other teams.
This news article is drawn from three published on the University of Oxford News and Events page, with permission.
Images: health worker donning gloves at Médecins Sans Frontières health centre (© Caitlin Ryan/MSF); Ebola virus (© Festa via Shutterstock); volunteer receiving vaccine in Oxford (© Rob Judges/Oxford University Images); all with kind permission.