Phase 1 and Phase 1/2 Clinical Trials for Treatment of COVID-19-Associated ARDS by AV-001, a Novel Therapeutic Targeting Vascular Endothelium
Abstract
Topic Area: Our proposed research and development address the FY20 PRMRP Respiratory Health Topic Area titled, “Novel and/or innovative detection technologies or therapeutics to reduce the incidence and/or severity of ARDS and/or other lung injury secondary to trauma, transfusion, mechanical ventilation, infection, burns, hemorrhagic shock, inhalation, and/or oxygen exposure.” A Pervasive Medical Problem: Acute Respiratory Distress Syndrome (ARDS) is a debilitating and lethal syndrome defined by specific clinical criteria demonstrating a major build-up of fluid in the lungs. ARDS occurs as a response to or an escalation of various lung injuries, including direct insults to the lungs, such as viral or bacterial pneumonia, or indirect insults to the lungs, such as sepsis or cardiopulmonary bypass. It is also a common syndrome, occurring in approximately 10 percent of all patients admitted to hospital Intensive Care Units and 23 percent of all patients who are placed on mechanical ventilation. The annual incidence alone is over a quarter of million patients with a mortality rate of approximately 40 percent. Compounding the issue is the lack of effective medicines. Care focuses on what is called “supportive therapy,” referring to fluid management and/or further injury prevention via lung-protective ventilation. Today, there are no targeted therapeutics in the market to treat ARDS. There are also significant socioeconomic ramifications, as ARDS patients have an average stay in the hospital of 17 days, resulting in an annual cost of approximately 10 billion dollars. Relevance to the Current COVID-19 Pandemic: Among patients hospitalized due to COVID-19, up to 40 percent will likely acquire ARDS. Currently, the leading cause of death instigated by a SARS-CoV-2 infection is the accumulation of fluid in the lungs and decreased capacity to breathe, known as ARDS. Importantly, it has been noted that COVID-19-instigated ARDS is analogous to general ARDS (i.e., ARDS resulting from other lung injuries). Consequently, pharmaceuticals developed for general ARDS hold clinical relevance and important clinical utility to COVID-19 patients. A Solution to the Crux of the Problem: Vasomune Therapeutics has developed a novel drug candidate AV-001 for treatment of ARDS that addresses a critical driver of the syndrome, i.e., the accumulation of fluid in the lungs due to increased permeability of lung microvasculature. This occurs due to loss of barrier integrity of critical cells lining the microvasculature, known as endothelial cells. This loss of barrier integrity causes fluid to drain into the lungs and reduces the capacity of the lungs to provide life-giving oxygen to the blood supply, which drives lung dysfunction, frequently culminating in death. AV-001 interacts with a pathway, known as the Tie2/Angiopoietin signaling axis, thus promoting barrier integrity of endothelial cells, defending the lungs from vascular leakage. Overall Objective: Vasomune Therapeutics has conducted extensive research in various different animal models that cumulatively suggest the vast potential of AV-001 as a targeted therapeutic against ARDS. Here, we seek to translate our preclinical findings to early clinical trials and considering the exceptional circumstances around the COVID-19 pandemic and the emergency context seek emergency use authorization from the FDA. In our proposed project, we will first run a phase 1 safety clinical trial and if safety endpoints are met, we will also run a phase 1/2 proof-of-concept efficacy trial in patients with moderate-to-severe COVID-19. This course of action is justified as new research suggests that biomarkers for dysregulation of the Tie2/Angiopoietin signaling axis are elevated in hospitalized COVID-19 patients. Consequently, Vasomune’s novel approach to treat COVID-19 patients at (significant) risk for ARDS or that already are affected by ARDS is treatment with AV-001 to reinforce the barrier integrity of end
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110834
Entities
People
- Douglas S. Hamilton
Organizations
- United States Army