The Liberia-U.S. Joint Partnership for Clinical Research has announced that a clinical study of two experimental vaccines to protect against Ebola will begin in Liberia today. The Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) study is designed to determine if giving a single dose of a test vaccine will prevent Ebola virus disease (EVD). The two vaccines to be tested in this study are the ChAd3-ZEBOV vaccine, manufactured by Glaxo SmithKline, and the rVSV-ZEBOV vaccine, manufactured by Merck/NewLink.
The PREVAIL study originated with a request last August from the Liberian Minister of Health to the U.S. Secretary of the Department of Health and Human Services to form a joint clinical research partnership to accelerate the development of vaccines to prevent Ebola and medicines to treat people with EVD. When this collaboration began in October 2014, EVD was ravaging Guinea, Liberia, and Sierra Leone.
The uncontrolled outbreak prompted a World Health Organization (WHO) panel of experts to advise the global scientific community to accelerate the development of Ebola vaccines and treatments without compromising international standards for safety and efficacy. The two vaccines selected for this study were recognized by the WHO panel as being at the most advanced stage of development.
“This initiative represents an important entry into the global clinical research arena for Liberia and an enduring symbol of the strong ties that exist between Liberia and the United States,” Dr. FatormaBolay, Liberia’s Co-Principal Investigator for the study said. “Most importantly, it shows the invaluable significance of a combined global effort to find safe and effective vaccines to control the spread of this devastating disease and prepare the world to prevent future epidemics,” he added.
The PREVAIL study protocol has been diligently reviewed for scientific rigor and ethics, and has been approved by the U.S. Food and Drug Administration (FDA), an Institutional Review Board of the U.S. National Institutes of Health, the National Research Ethics Board of Liberia, and the Liberia Medicines and Health Products Regulatory Authority.
Approximately 27,000 healthy adult volunteers are expected to participate in the PREVAIL study at 10 or more clinical centers in and around Monrovia, Liberia. Study participants will be assigned at random, or by chance, into one of three groups to receive either the ChAd3-ZEBOV vaccine, the rVSV-ZEBOV vaccine, or a saline (saltwater) injection, known as a placebo. Each group will have about 9,000 people. Neither the volunteer nor the study staff will know which vaccine or placebo has been administered until the end of the study. All participants will be given advice on how to avoid being infected with Ebola.
This type of study design called a randomized controlled study, compares the results from the volunteers who receive the experimental vaccines against the results from those who receive the placebo (control). If one or both of the test vaccines are safe and effective, it is expected that those volunteers who received those vaccines will be protected from the EVD.
In developing the study, the study sponsor, the U.S. National Institute of Health, thoroughly considered concerns expressed about the ethics of exposing a subset of otherwise healthy people participating in the trial to a placebo control that offers no protection against EVD. The randomized placebo-controlled design is considered the most powerful for determining if a test vaccine or treatment is effective, however, and the use of a placebo is considered scientifically appropriate and ethical when no other approved medical alternative exists. The PREVAIL study will ensure that study participants receive the optimum standard of care available in the country should they either become infected with the Ebola virus or develop any unexpected or dangerous reactions to the vaccine (adverse events).
The first 600 vaccinations will occur at the newly renovated clinical research unit of the Redemption Hospital in New Kru Town. Volunteers will be given a detailed explanation of the purpose of the study, what procedures the study entails (e.g., collection of urine and blood samples), the side effects or discomforts that could occur after receiving the vaccination, and any possible benefit that could come from their participation. Each volunteer will be given the opportunity to have their questions answered before making their own decision about whether or not to participate. This informed consent process, which has been thoroughly reviewed by research ethics boards in Liberia and the U.S., will occur with every potential participant.
Those who join the study must first sign an informed consent form before any study procedure or vaccination is performed. Potential volunteers will be advised that they are at liberty to decline participation or withdraw their consent at any time without consequence.
All participants will be closely monitored by the study staff. An independent Data and Safety Monitoring Board of medical and scientific experts from the U.S. and Liberia will also periodically review data collected from study participants to ensure their safety.
The clinical development process for the test vaccines began with Phase 1 testing for safety (assessment of side effects or adverse events) in a small number of human volunteers. Several Phase 1 studies of Chad3-ZEBOV and rVSV-ZEBOV have been conducted and most of the adverse events reported in these studies were mild and did not last long. A few study volunteers experienced fever and joint pain that lasted for a few days and ended within two weeks. Most people who received the vaccines in these studies developed infection-fighting proteins, or antibodies, that might help to protect them from getting EVD.
The Liberia-U.S. Clinical Research Partnership team has worked diligently over the past three months with leaders and members of various Liberian communities to ensure that the initiation and conduct of the PREVAIL study are locally and nationally appropriate. In addition to Dr. Bolay, the study is being led by Stephen Kennedy, MD, MPH, FLCP, Liberia Co-Principal Investigator, and from the United States H. Clifford Lane, M.D., Clinical Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health.