(c) 2016 Jon L Gelman, All Rights Reserved.

Saturday, March 28, 2015

Ebola Test Vaccines Appear Safe in Phase 2 Liberian Clinical Trial

The National Institutes of Health has announced the advancement of two experimental vaccines for Ebola. This is a major announcement that will provide additional safety for healthcare workers and populations exposed to this deadly disease.

Liberia-U.S. Partnership Planning Phase 3 Trial and Study of Ebola Survivors

Two experimental Ebola vaccines appear to be safe based on evaluation in more than 600 people in Liberia who participated in the first stage of the Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) Phase 2/3 clinical trial, according to interim findings from an independent Data and Safety Monitoring Board review. Based on these findings, the study, which is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, may now advance to Phase 3 testing.

“We are grateful to the Liberian people who volunteered for this important clinical trial and encouraged by the study results seen with the two investigational Ebola vaccine candidates,” said NIAID Director Anthony S. Fauci, M.D. “Now we must move forward to adapt and expand the study so that ultimately we can determine whether these experimental vaccines can protect against Ebola virus disease and therefore be used in future Ebola outbreaks.”

The PREVAIL trial, which began on Feb. 2, 2015 in Monrovia, Liberia, is testing the safety and efficacy of the cAd3-EBOZ candidate vaccine co-developed by NIAID scientists and GlaxoSmithKline, and the VSV-ZEBOV candidate vaccine developed by the Public Health Agency of Canada and licensed to NewLink Genetics Corporation and Merck. Volunteers are assigned at random to receive a single injection of the NIAID/GSK (cAd3-EBOZ) vaccine, the VSV-ZEBOV vaccine, or a placebo (saline) injection. The trial is also double-blinded, meaning that neither study subjects nor staff know whether a vaccine or placebo was administered. A randomized, double-blind, placebo-controlled trial is considered the “gold standard” in clinical research.

While the initial enrollment goal in the Phase 2 study has been met and the vaccines proven safe, the researchers are continuing Phase 2 study enrollment at Redemption Hospital in Monrovia, Liberia, through late April 2015. This would boost enrollment in the Phase 2 portion of the trial to approximately 1,500 people and would be done, in part, to increase the percentage of women (currently, about 16 percent) in the study for a more robust data set overall. The study follow-up period would be at least one year, and two additional blood samples would be obtained from all volunteers at six and 12 months post-vaccination to determine the durability of the immune responses. These proposed changes will be discussed with the U.S. Food and Drug Administration and are under review by the institutional review boards in Liberia and the United States.

Investigators planned to enroll 27,000 people in Liberia at risk of Ebola infection in the Phase 3 portion of the trial. However, there has been only one new confirmed case of Ebola infection in the country since Feb. 19, 2015. Given this decline in Ebola infection incidence, the trial leaders—H. Clifford Lane, M.D., NIAID deputy director for clinical research, and Liberian co-principal investigators Stephen Kennedy, M.D., and Fatorma Bolay, Ph.D.—have determined that it is scientifically appropriate to expand the trial to additional sites in other West African countries. Discussions are underway to explore that possibility.

The Liberia-U.S. research team also plans to launch a separate natural history study of Ebola survivors to better understand the after-effects of Ebola virus disease. Four sites in Monrovia, Liberia and locations in the United States may begin enrollment into this study in the coming months, pending regulatory review and approval. More information on this study will be provided when the trial launches.