FLC | iTHRIV helps refocus Navy-developed oxygenation drug for COVID-19

iTHRIV helps refocus Navy-developed oxygenation drug for COVID-19

May 4, 2020

Diffusion Pharmaceuticals Inc. a biotechnology company developing new treatments for life-threatening medical conditions by improving the body’s ability to deliver oxygen where it is needed most, today announced the pre-IND submission to the U.S. Food and Drug Administration (FDA) of a planned clinical program using trans sodium crocetinate (TSC) in COVID-19 patients displaying severe respiratory symptoms and low oxygen levels.

Clinical trial start-up preparations are continuing as the Company awaits the FDA’s response. To aid in timely trial enrollment, Charlottesville, Virginia-based Diffusion is conducting expedited discussions with institutions located in areas of severe COVID-19 incidence, both in the U.S. and in Eastern Europe, to determine their possible participation.

Diffusion’s COVID-19 program is a cooperative research effort with the University of Virginia Health System (UVA) and the Integrated Translational Research Institute of Virginia (iTHRIV.) iTHRIV is a National Institutes of Health (NIH)-funded Clinical and Translational Awards (CTSA) program. TSC was originally developed in conjunction with the Office of Naval Research to address systemic hypoxia from blood loss on the battlefield.

Acute Respiratory Distress Syndrome (ARDS) develops in nearly all patients hospitalized with COVID-19, triggered by lack of sufficient oxygen to vital organs as a consequence of damage to the lungs. In severe cases, patients need to receive life support through mechanical ventilation. In general, ARDS carries a high mortality rate (up to 40% in those on a breathing machine, and likely higher in COVID-19-related ARDS). Diffusion scientists believe that through successful implementation of its TSC/COVID-19 clinical program, TSC’s oxygen-enhancing mechanism of action could provide an important new treatment option for this life-threatening unmet medical need. Further, they believe that TSC’s novel mechanism of action would be compatible with many of the COVID-19 treatment modalities currently used or under development.

Although the number, design and projected enrollment of the clinical trials are subject to change, Diffusion’s pre-IND submission for TSC envisions three studies to be conducted in rapid succession. The first is an open-label study that will examine the basic safety of the TSC dosing paradigm in up to 12 COVID-19 patients who have been admitted to Intensive Care Units (ICUs). Blood gas and pulse oximetry data also will be collected to observe associations between TSC and oxygenation levels in these oxygen-starved patients.

The second trial is planned as a larger, double-blinded, randomized, placebo-controlled study to confirm safety in the ICU patient population and determine the statistical significance of any TSC effect on the patient’s oxygenation status, again using blood gas analysis and pulse oximetry. The number of patients enrolled will be determined by statistical considerations. Data also will be collected for other endpoints including mortality.

Assuming the results from the second study warrant program continuation, the third study, also double-blinded, randomized, and placebo controlled, is intended to be a registration trial. The third trial would enroll a statistically determined number of hospitalized COVID-19 patients not yet admitted to an ICU, and who therefore may not have arterial blood lines in place. While pulse oximetry readouts and other parameters will be monitored for possible improvements in patient status, the primary goal of this third study will be to show that TSC lowers the probability of COVID-19 patient admittance to the ICU.

Diffusion scientists believe achieving this goal would help healthcare professionals prevent the cascade of negative effects from oxygen deficiency in hospitalized COVID-19 patients, which too often lead to disease progression and mortality. Meeting this goal could also provide significant cost savings to the health care system, lessening the use of critical resources associated with ICU admittance and fostering TSC’s more widespread use.