Periodic Reporting for period 3 - REACTION (Evaluation of the efficacy and of the antiviral activity of T-705 (favipiravir) duringEbola virus infection in non-human primates humans)
Reporting period: 2016-11-01 to 2017-10-31
The overall objectives of REACTION!:
• Deliver evidence for the effective and safe use of FAV for the treatment and prevention of EVD in patients through a human Phase 2b trial with Ebola infected patients;
• Deliver additional scientific data on the tolerance, optimal dose and administration timings of FAV in non-human primates infected with EBV to optimize use of FAV in the current and for further outbreaks;
• To assure successful application of FAV in a large group of Ebola patients directly after this project if the drug shows efficacy;
• A platform of translational research on Ebola in West Africa, including European and African researchers and technicians from various fields, and anticipate future studies that will have to be done after our trial is finished;
• Train and educate local aid professionals and the community to ensure social mobilization and community engagement.
The secondary objectives are: to assess the efficacy of FAV in decreasing plasma RNA and infectious loads; to assess the tolerance of the drug; and to describe the evolution of viral subpopulations of EBOV (including the analysis of mutations potentially associated with antiviral resistance) using deep sequencing approaches.
The REACTION! Project was divided into 5 scientific work packages, supported by one further work package around dissemination, management and coordination.
Overall, the conclusions of the action were that there was a good tolerance of FAV and the relationship with the local communities as well as the NGOs has been excellent. Further research is necessary to better understand of FAV pharmacokinetics as well as testing of higher doses relevant for the EBOV. The REACTION! Consortium has also published extensively – with no less than 25 project related publications. Work continues beyond the lifetime of the project focusing on research and engagement has now moved into further prevention of the EBOV.
Our results are published in no less than 25 book chapters/scientific publications. In the years during and following the JIKI-trial, we have disseminated our work at international conferences. Our expertise in clinical trials in emergency situation is called upon in many follow-up emergency trials.
Whilst the results of the FAV clinical trial were shown not to be conclusive, it has been very important to show the effect of FAV on the viral replication in patients with a Ct≥20 or a viral load below 108 genome copies/ml. The JIKI trial, performed in an international emergency situation, was unrandomized and provided immediate care to patients with EVD; it realized improved care for Ebola patients through the clinical trial, and improved broader scientific literacy.
In future studies, further trials should be powered, to show that monotherapy with FAV decreases mortality by at least 30%. It may also be of interest to evaluate higher doses than used in the JIKI trial as well as investigating possible combination therapies.
Other initiatives have been started to continue research on treatment of EVD in patients. Additionally, the trial team has contributed actively to the epidemiologic investigations of the last clusters of EVD beyond the epidemic in Guinea - including the FORCE, PREVAC and PREVAIL II trials.