"Conducting clinical trials 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."
In the absence of specific treatments for Ebola, international medical humanitarian organisation Médecins Sans Frontières/Doctors Without Borders (MSF) announced today that it will host clinical trials in three Ebola treatment centres in West Africa.
The separate trials, which are aimed at quickly finding an effective therapy that can be used against the disease which has so far taken around 5,000 lives in the current outbreak in the region, will be led by three different research partners.
Different focus between research partners
The French National Institute of Health and Medical Research (INSERM) will lead a trial using antiviral drug favipiravir in Guéckédou, Guinea; the Antwerp Institute of Tropical Medicine (ITM) will lead a trial of convalescent whole blood and plasma therapy at the Donka Ebola centre in Conakry, Guinea; and the University of Oxford will lead, on behalf of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), a Wellcome Trust-funded trial of the antiviral drug brincidofovir at a site yet to be determined.
The World Health Organization (WHO) and health authorities of the affected countries are also taking part in this collaborative effort.
Minimal disruption to patient care
“This is an unprecedented international partnership which represents hope for patients to finally get a real treatment against a disease that today kills between 50 and 80 per cent of those infected,” said Dr Annick Antierens, who coordinates the investigational partnerships for MSF.
“As one of the principal providers of medical care to Ebola patients in West Africa, MSF is taking part in these accelerated clinical trials to give people affected by the current outbreak a better chance of survival.”
The trials’ protocols are in the final stages of development and are designed with a simple target of 14-day survival and with broad inclusion criteria. The protocols will ensure that disruption to patient care will be minimal, that internationally-accepted medical and research ethical standards are respected, and that sound scientific data will be produced and shared for public good.
The main principles and designs have been shared with the respective countries’ ethical authorities, with the goal of starting the first trials during December 2014. Initial results could be available in February 2015.
'Critically important trials'
The two drugs, brincidofovir and favipiravir, were selected from WHO’s shortlist of potential Ebola treatments after careful review of safety and efficacy profiles, product availability, and ease of administration to patients.
Professor Peter Horby, the Chief Investigator of the ISARIC-led 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.”
"We need to do all we can to try the products available today to increase the chances of finding an effective treatment against Ebola" - Dr Annick Antierens
Reactive discussion between teams
“These three trials are part of the first phase of a research aimed at finding the best treatment to cure patients with Ebola,” said Professor Denis Malvy, who will lead the INSERM trial in Guinea.
“The three trial boards will therefore be coordinated in a very reactive way, so that any new fact can be discussed rapidly and our research plans can be adapted accordingly.
“Strengthening the link between our teams is all the more important as there is the possibility that, should our trials give positive results, the next phase could consist of combining interventions.”
Ebola survivors key to new treatment
Trial of convalescent whole blood and plasma therapy will consist of administering blood or plasma, containing antibodies from survivors, to infected patients. This approach is also endorsed by WHO.
“Convalescent plasma from recovered patients, containing antibodies against pathogens, has been safely used for other infectious diseases,” said ITM’s Johan van Griensven, coordinating investigator of the trial.
“We want to find out whether it works for Ebola, whether it is safe and whether it can be scaled-up to reduce the number of deaths in the current outbreak. Close communication with people who recovered from Ebola, and the community at large, will be vital for a successful trial.
“We hope that recovered patients donating blood and plasma to help sick people could reduce fear of the disease and reduce stigmatisation of those who survived.”
'No guarantee' of cure
When other experimental or off-label products with promising efficacy and safety data become available, they will be assessed with the view of proposing further trials in other MSF Ebola management centres in the region.
All three trials will prioritise community engagement and informed consent from patients or their representative. Each patient who consents to be part of a trial will have the potential risks of being subjected to a new therapy clearly explained.
“We need to keep in mind that there is no guarantee that these therapies will be the miracle cure,” added MSF’s Dr Antierens. “But we need to do all we can to try the products available today to increase the chances of finding an effective treatment against Ebola."
Pressure on drug developers
While clinical trials are underway, MSF is urging the drugs’ developers to scale up production supply now, to ensure there is no gap between the end of the trials and the large-scale introduction of products found to be safe and effective.
MSF is also urging drug manufacturers to ensure that end products are affordable and available in the quantities needed to tackle the outbreak at its epicentre in West Africa.
Distribution of end products should be driven by needs, irrespective of where people live or the capacity of a country to pay.