Novel Pharmacological Interventions for ARDS of COVID-19 Patients: Investigational New Drug-Enabling Studies
Abstract
COVID-19, a pandemic that began in December 2019 and has since infected over seven million people worldwide as of June 2020, is caused by the virus SARS-CoV-2, which is closely related to the viruses that caused the SARS and MERS outbreaks of 2003 and 2012, respectively. This virus, thought to have first infected humans from contact with animals, is now primarily spread from person to person through droplets in the air produced when an infected person coughs, sneezes, or exhales. The virus then infects the lungs where it causes damage and inflammation, which can lead to a feared condition called acute respiratory distress syndrome or ARDS. The virus can also enter the bloodstream and cause the body to react too aggressively to the virus, damaging itself in the process. This condition is called cytokine storm, named after the substances, called cytokines, that are overproduced by the body in response to the virus. Together, ARDS and cytokine storm are thought to be the leading causes of death and disability in patients who have COVID-19. Currently there are no drugs that have been proven to treat either ARDS or cytokine storm in COVID-19 patients. We propose that a new drug, called VT-109, could protect the lung from the damaging effects of the SARS-CoV-2 virus as well as reduce the overreaction of the body in cytokine storm. In studies done with mice that have been designed to replicate these complications of COVID-19, we have shown that our drug has restored function to the damaged lungs and reduced the cytokine levels in these mice as well as improved overall survival in infected mice. Based on these findings, we believe that VT-109 could be a particularly useful treatment for COVID-19 patients, and it would be the first of its kind. In order to advance this drug to clinical trials in human patients, we propose to perform the following studies with funding from the PRMRP Technology/Therapeutic Development Award for Emerging Viral Diseases and Respiratory Health. Aim 1: We will use mice designed to replicate what COVID-19 is like in humans as well as monkeys as they are genetically similar to humans in order to test how effective our new drug, VT-109 is in treating the effects of COVID-19 on the lung and body and to measure the proper dosage of the drug. We will also measure the amount of virus present in the animals during the course of treatment to determine whether or not the drug affects how long the animals are infected. Aim 2: In order to make sure the drug will be safe to test in humans we will study whether or not VT-109 can cause mutations in the DNA of bacteria and of human and mouse cells. These tests will help determine whether or not there is a risk for this drug to cause cancer. Aim 3: We will use rats and monkeys to determine how long the drug stays in the bloodstream and whether or not it has negative effects on the heart. Aim 4: To find out how much VT-109 is safe to give, we will determine the maximum level of the drug at which there are no bad effects in monkeys. If the level is acceptably high enough, we will continue with studies measuring the effects of repeated dosing with our drug. Aim 5: In preparation for the first clinical trials in humans, we will establish an optimized design for manufacturing the drug according to a set of principles called Good Manufacturing Practice (GMP). We will also create quality control methods and produce enough drug to use in clinical trials in accordance with GMP. Aim 6: We will develop accurate methods to analyze the dosage of the drug in the format that it will be administered during our studies in rats and monkeys. We will develop this test in accordance to a set of principles called Good Laboratory Practice (GLP) and validate it as required by the FDA. Additionally, we will develop a second test to accurately measure the level of our drug in the bloodstream of rats and monkeys in our studies. Aim 7: As a follow-up to Aim
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110639
Entities
People
- Yulia Komarova
Organizations
- United States Army
- University of Illinois at Chicago