Phase 2 Clinical Evaluation of USB002 (Angiotensin 1-7) for the Treatment of Pulmonary Distress Due to COVID-19
Abstract
Study Objectives and Rationale: Patients who develop serious infections from COVID-19 typically develop severe acute respiratory syndrome (SARS), which is characterized as acute respiratory distress syndrome (ARDS) due to inflammation and damage to the lungs, heart, liver, and kidneys, which ultimately may result in organ failure and death. With the number of COVID-19 cases increasing exponentially and resultant mortality (now surpassing 100,000 American deaths in 3 months, which is more people than died in all wars involving the U.S. military since the Korean War), the need for an effective therapy is urgent. COVID-19 infection affects a hormone system in the human body. Hormone systems work by maintaining the body’s balance in normal situations and providing responses in situations of stress or danger. The renin-angiotensin system (RAS) works like a hormone system in tissues that make up the lung, heart, and kidneys. Normally, proteins made by other organs (including the liver) are carried into tissues by blood using the vascular system to provide substances that can be changed by RAS into a hormone called angiotensin 1-7 [A(1-7)]. This hormone allows for the tissues inside of the organs to work normally. However, the COVID-19 virus stops RAS from working. As a result, the substances that are usually changed by the RAS into A(1-7) build up into dangerously high concentrations, and tissues in the lungs, heart, and kidneys have dangerously low concentrations of A(1-7). Without A(1-7) in their tissues, normal functions of the lungs, heart, and kidneys are reduced and eventually stop all together. Reddy (2019) showed that ICU patients with ARDS who had reduced A(1-7) serum levels did not survive. The goal of this study is to see if A(1-7) administered into the vascular system is able to correct deficient concentrations of A(1-7) caused by the COVID-19 virus, ultimately restoring normal function of the lungs, heart, and kidneys. Our pharmaceutically formulated A(1-7) has been evaluated in seven clinical trials of subjects with breast cancer, chronic kidney disease, and healthy volunteers. To date, 98 subjects have been treated with A(1-7). A(1-7) has been well-tolerated with no drug-related serious adverse events noted to date. The treatment of SARS-CoV-2-induced ARDS with A(1-7) via IV infusion has the potential to be an effective and safe therapeutic method to reducing pulmonary distress, thereby decreasing fatality rates, improving long-term patient outcomes, and freeing up ICU resources. In animal studies, SARS-infected animals experienced higher levels of Ang II due to reduced proteins that create A(1-7). Other animal studies show that A(1-7) is potentially a safe way to stop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced life-threatening inflammatory responses in the lung, heart, kidneys, and brain. Overall, our goal is to determine the safety and tolerability of A(1-7) in the treatment of respiratory distress from COVID-19 infection. We will do this by determining the maximum tolerated dose (MTD) of A(1-7) and then use that MTD to determine the efficacy of A(1-7) in the treatment of respiratory distress from COVID-19 infection. If A(1-7) treatment is safe and effective in treating the respiratory and cardiac distress caused by COVID-19 infections, we will be able to make it available to every healthcare center through an agreement with the FDA for Emergency Use Authorization. Topic Areas: This application specifically focuses on a pharmacological intervention for COVID-19-induced complications, including ARDS and related sequelae in the area of Emerging Viral Diseases and Respiratory Health. Specifically, within the Emerging Viral Diseases topic area, we plan to use our knowledge of the mechanism of COVID-19 and its impact on the body to find a treatment for respiratory distress. We plan to prevent ARDS caused by COVID-19, develop better methods for treating lung in
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110025
Entities
People
- Gere Dizerega
Organizations
- United States Army