Exploring Dose and Schedule Variations of a Novel Dengue Antiviral Prophylaxis Intervention to Support US Military Operational Requirements
Abstract
Dengue is an emerging and re-emerging infectious disease caused by infection with any of the four dengue virus (DENV) types. The viruses are transmitted by the Aedes species of mosquito as they take a blood meal from a DENV infected person and, after a couple of days, can then transmit the virus to another person. There are an estimated 396 million DENV infections every year occurring in over 125 countries. Approximately 96 million infected people require medical care for their illness. A small percentage of people (2%-4%) who are experiencing a second DENV infection with a different DENV type will develop severe dengue. In severe dengue, people can have bleeding problems and leaky blood vessels causing dangerously low blood pressure and shock. Between 8,000-20,000 people die each year of dengue; most are young and healthy before infection. Dengue occurs in tropical and subtropical countries in the Americas, Africa, parts of the Middle East, and South and Southeast Asia. The U.S. Service Member deploys to, and travelers visit, many of these areas and they are, therefore, at risk of infection. Based on blood tests, 5%-13% of the frequently deploying Service Members (i.e., special operations) have already experienced one DENV infection and approximately 1.5% of individuals will experience a DENV infection during their first deployment. Safe and effective means of preventing and treating infection are needed. We propose to test an experimental Janssen Dengue Drug with promising anti-DENV activity. Our team intends to advance the development of an experimental Janssen Dengue drug designed to prevent or reduce the severity of a dengue infection by preventing or reducing viral replication. We believe severe DENV infections occur and some infected people become severely ill due to high levels of viral replication after infection. The high replication levels cause a cascade of events making infected people severely sick and potentially leading to death. Therefore, if we can administer a drug that interrupts DENV replication before high level replications begins, it may be possible to prevent or substantially reduce DENV replication such that illness does not occur or severe infections are prevented. We will test the experimental Janssen Dengue Drug in a two-part study. In the first part, volunteers will receive a specific dose of the experimental Janssen Dengue Drug or placebo; neither the volunteer nor the study team will know which one the volunteer receives. After a few days of receiving the drug/placebo, each volunteer will be experimentally infected by a one-time injection of an attenuated live DENV-1 virus strain. After injection, we will measure a number of safety markers, indicators of viral replication, and the immune response to infection. By comparing how the various doses of the experimental Janssen Dengue Drug impact the virus replication compared to placebo (i.e., lower viral replication), we will understand the drug’s potential to work in a real-world setting. We will select the safest and best performing doses from part one and then complete the second part of the study. In the second part, we will further define safety and explore the optimal dose and dosing schedule with a focus on improving ease of administration for an operational military population. Experimental infection of humans with dengue has been a research tool for over 100 years, and we have been working with the DOD to make this tool widely available to support dengue vaccine and drug development. The tool is designed to improve overall safety (i.e., expose fewer volunteers to experimental interventions) and speed of development timelines (i.e., acquire important information sooner). We have safely completed two experimental infection studies at our institution, and a third study is currently ongoing. The success of our proposal and experiments will yield very important information about how an experimental Janssen Dengue Drug may be a
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110800
Entities
People
- Stephen J Thomas
Organizations
- State University of New York Upstate Medical University
- United States Army