Question & Answer:
PREVAIL Phase 2/3 Clinical Trial of Investigational Ebola Vaccines
PREVAIL stands for Partnership for Research on Ebola Vaccines in Liberia. It is a Phase 2/3 clinical trial designed to evaluate the safety and efficacy of two investigational vaccines intended to prevent Ebola virus infection: the NIAID/GSK investigational Ebola vaccine and the VSV-ZEBOV investigational Ebola vaccine. The trial is being led by a recently formed Liberia-U.S. clinical research partnership and is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
The trial is being co-led by Stephen B. Kennedy, M.D., M.P.H., Secretary-General of the Liberia College of Physicians and Surgeons, Fatorma Baloy, Ph.D., Director, Liberian Institute for Biomedical Research, and H. Clifford Lane, M.D., NIAID’s Deputy Director for Clinical Research and Special Projects. The pharmaceutical company GlaxoSmithKline (GSK), based in Research Triangle Park, N.C., will supply the NIAID/GSK vaccine candidate, and the Merck Corp., headquartered in Kenilworth, N.J., will supply the VSV-ZEBOV test vaccine.
The PREVAIL trial will take place in and around Monrovia, Liberia. Liberia is one of the three countries that has been most severely impacted by the Ebola epidemic in West Africa. Ultimately, the clinical trial will involve 10 vaccination centers within existing health clinics in the Monrovia area. Depending on the course of the Ebola epidemic, additional sites may be added.
The trial is expected to enroll approximately 27,000 healthy men and women aged 18 years and older. Women who are pregnant or breastfeeding cannot enroll, nor can men and women who have recovered from Ebola infection. In addition to seeking healthy adults, the trial will seek to enroll people who are at particular risk for Ebola infection, including health care workers, individuals living in communities with ongoing transmission, contact tracers, members of burial teams and ambulance drivers.
The NIAID/GSK Ebola vaccine candidate, also called cAd-EBOZ, is based on a harmless, recombinant chimpanzee cold virus, called chimpanzee adenovirus type 3 (cAd3) that is used as a carrier, or vector, to deliver segments of genetic material derived from the Zaire strain of Ebola virus. The Zaire species of the virus has caused the current Ebola outbreak in West Africa. The vaccine delivers one part of the Ebola genetic material to human cells, but the adenovirus vector does not replicate. Rather, the Ebola gene that it carries allows the cells of the vaccine recipient to express a single Ebola protein, and that protein prompts an immune response in the individual.
Nancy J. Sullivan, Ph.D., chief of the Biodefense Research Section in NIAID’s Vaccine Research Center (VRC), working in collaboration with a team of VRC researchers and scientists at the Army Medical Research Institute of Infectious Diseases and Okairos, a Swiss-Italian biotechnology company acquired by GSK in 2013, developed the vaccine.
In published interim results from Phase 1 testing conducted at the NIH Clinical Center in Bethesda, Md., the experimental vaccine was safe and produced immune system responses predictive of protection in all 20 healthy adults who received it. Similarly, in published results from Phase 1 testing conducted at Oxford University, the NIAID/GSK vaccine produced similar results in terms of safety and immune response.
Initial data from these trials have informed the study design for the PREVAIL Phase 2/3 Ebola vaccine trial.
The VSV-ZEBOV Ebola vaccine candidate is based in part on a genetically engineered version of vesicular stomatitis virus (VSV), an animal virus that primarily affects cattle. Human VSV infections are rare and generally produce three to four days of mild illness. In the VSV-ZEBOV investigational vaccine, the gene for the outer protein of the vesicular stomatitis virus has been replaced with a segment of the gene for the outer protein of the Zaire Ebola virus species.
Researchers at the Public Health Agency of Canada’s National Microbiology Laboratory developed the vaccine and licensed it to NewLink Genetics Corp, based in Ames, Iowa. NewLink entered into a licensing and collaboration agreement with Merck to conduct further testing of the vaccine.
In October 2014, NIAID and the Walter Reed Army Institute of Research began simultaneous Phase 1 safety and immunogenicity testing of the VSV-ZEBOV vaccine candidate. Safety data from those studies have not yet been published, but sufficient safety and immune response data exist to move the vaccine forward for Phase 2/3 testing.
Can either of the two investigational vaccines cause a study participant to become infected with Ebola?
No. The Ebola genetic material contained in the experimental vaccines cannot cause someone to become infected with Ebola because it is only a small piece that by itself is not infectious.
The PREVAIL study is a Phase 2/3 randomized, double-blind, controlled, three-arm clinical trial. A randomized, double-blind, placebo-controlled trial is considered the “gold standard” in clinical research because it is the most rapid and reliable way of determining if an intervention is safe and effective.
Both the NIAID/GSK experimental vaccine and the VSV-ZEBOV vaccine candidate will be compared to placebo. The initial Phase 2 portion of the trial will involve administering the investigational vaccines in a single injection among 600 study participants in an effort to collect more detailed safety and immune response data about both vaccines. Participants in Phase 2 will undergo blood draws, adverse event assessments and monitoring for signs and symptoms of Ebola infection at one week and one month after vaccination, and then monthly thereafter. In the absence of major safety issues, enrolment will continue and the remaining volunteers will be randomly assigned in three, equal-sized groups to the Phase 3 portion of the clinical trial.
The Phase 3 portion of the trial is designed to evaluate the ability of each of the vaccines to protect against Ebola infection and provide an accurate assessment of the benefits and risks associated with each candidate vaccine. Participants in each of the three Phase 3 study arms will receive a single injection of one of the two test vaccines or placebo and will undergo monthly assessments for adverse events and signs and symptoms of Ebola infection. All participants in both the Phase 2 and 3 portions of the trial will be followed for 8 to 12 months.
The well-being and safety of study participants is our top priority. The protocol to conduct the trial was reviewed and approved by Liberian health and regulatory officials, NIAID, and the U.S. Food and Drug Administration. These reviews ensured that the study would be scientifically, ethically, and clinically appropriate and that it would adhere to accepted standards for protecting human clinical research participants. Volunteers who meet the study’s eligibility criteria must provide oral and written informed consent to participate. Throughout the course of the trial, an independent data and safety monitoring board comprised of clinical research experts, statisticians, ethicists and community representatives will meet at regular intervals through the study to review data as it is gathered.
If a study participant becomes infected with Ebola during the course of the clinical trial, he or she will be directed to medical care for treatment.
Although it is a much-welcomed development that Ebola is on the decline in Liberia, the potential for continued flare-ups and future Ebola outbreaks is real. A safe and effective vaccine that protects against Ebola infection could contribute significantly to containing the current Ebola situation in West Africa and would be a critically important tool in preventing future Ebola outbreaks. The PREVAIL trial may need to be adapted in the future, however, to address a continued reduction in the number of new Ebola cases in Liberia.
The trial is currently anticipated to be completed in June 2016.