Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries.

INTRODUCTION: The Ebola virus disease (EVD) outbreak in 2014-2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments. METHODS: This is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection. RESULTS: From April 2017 to December 2018, a total of 5002 volunteers were screened and 4789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4789 participants, 2560 (53%) were adults and 2229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years, 750 (16%) 5 to 11 years, and 930 (19%) aged 12-17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1090 participants was 72 (50, 116) EU/mL. DISCUSSION: The PREVAC trial is evaluating-placebo-controlled-two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children. TRIAL REGISTRATION: ClinicalTrials.gov NCT02876328 . Registered on 23 August 2016.

Advancing the Use of Mobile Technologies in Clinical Trials: Recommendations from the Clinical Trials Transformation Initiative.

Mobile technologies offer the potential to reduce the costs of conducting clinical trials by collecting high-quality information on health outcomes in real-world settings that are relevant to patients and clinicians. However, widespread use of mobile technologies in clinical trials has been impeded by their perceived challenges. To advance solutions to these challenges, the Clinical Trials Transformation Initiative (CTTI) has issued best practices and realistic approaches that clinical trial sponsors can now use. These include CTTI recommendations on technology selection; data collection, analysis, and interpretation; data management; protocol design and execution; and US Food and Drug Administration submission and inspection. The scientific principles underpinning the clinical trials enterprise continue to apply to studies using mobile technologies. These recommendations provide a framework for including mobile technologies in clinical trials that can lead to more efficient assessment of new therapies for patients.

Collaboration of the NIH and PHS Commissioned Corps in the International Ebola Clinical Research Response.

The U.S. response to the Ebola epidemic resulted in many federal agencies assessing their ability to respond to global threats and improve the efficiency of humanitarian efforts.

Considerations for Use of Investigational Drugs in Public Health Emergencies.

The paradigm for the use of investigational drugs in public health emergencies has been recently tested to prevent and treat highly infectious and lethal diseases. Examples include the successful implementation of vaccine and therapeutic clinical trials during the recent Ebola outbreak in West Africa. On the other end of the spectrum was the Emergency Use Authorization (EUA) of peramivir in the treatment of H1N1 influenza virus that did not provide an opportunity to collect data or understand the effectiveness of the EUA program. Between the gold standard of a randomized controlled clinical trial and the problems associated with EUAs are the domain of expanded access protocols that may provide an avenue to make products available while awaiting licensure. This paper will examine the regulatory pathways in the United States (US) for the use of investigational drugs in a public health emergency as well as considerations when making these products available outside the US. Descriptions of the applications of the various approaches will be presented. Regardless of the pathway chosen, public health and clinical research planners need to work together to consider several factors associated with the respective options and maintain a goal of working toward the collection of data to support licensure before faced with future outbreaks. Finally, this paper will consider the lessons learned from public health response in the context of investigational drugs in other diseases where "right to try laws" may pose opportunities, as well as challenges.

Establishment of a research pharmacy to support Ebola clinical research in Liberia.

OBJECTIVE: This article describes the establishment of a research pharmacy to support the Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) vaccine study for Ebola virus disease. SETTING: This article describes the establishment of the pharmacy element to support the overall research program during an Ebola outbreak in Monrovia, Liberia, in 2014 and 2015. PRACTICE INNOVATION: The need for the rapid establishment of infrastructure to support the Liberia-United States joint clinical research partnership in response to the emerging Ebola virus disease provided the opportunity for collaboration among Liberian and U.S. pharmacists. PRACTICE DESCRIPTION: Resource austere and research naïve. EVALUATION: Research pharmacy prepared and randomized 1500 vaccinations in support of PREVAIL. RESULTS: Experiences of the Liberian and U.S. pharmacists involved in the program are described. CONCLUSION: The partnership was successful in the conduct of the study. More importantly, the capacity for Liberian pharmacists to support clinical research was established. In addition, the U.S. team learned several important lessons that will help prepare them for responding to research needs in future infectious disease outbreaks.