UAB’s Hugh Kaul Precision Medicine Institute Research Leads to VA-Sponsored COVID-19 Clinical Trial Investigating Degarelix

Jun 11, 2020 | ARDS, COVID-19, Popular Posts, SARS-CoV-2, University of Alabama

UAB’s Hugh Kaul Precision Medicine Institute Research Leads to VA-Sponsored COVID-19 Clinical Trial Investigating Degarelix

Researchers out of the University of Alabama’s (UAB) Hugh Kaul Precision Medicine Institute played an instrumental role in identifying androgen deprivation therapy and hence the drug degarelix as a potential drug candidate to prevent SARS-CoV-2 virus from entering lung tissue and causing damage and a high risk of mortality. That drug has now entered a Phase II clinical trial sponsored by the U.S. Department of Veterans Affairs (VA) Office of Research and Development.

TrialSite News offers a brief overview of how some “medical detectives” at UAB helped uncover the possible reuse of an FDA-approved drug targeting COVID-19. 

The Genesis

As the COVID-19 pandemic unleashed its initial deadly fury in China, by January the research team at UAB’s Precision Medicine Institute, led by Matt Might, PhD, Professor of Medicine and Director of the Precision Medicine Institute, immediately moved into action leveraging substantial capabilities and tools: from artificial intelligence to computational genomics methods and models, reports Bob Shepard from UAB News.

The director commented, “One of our strengths is to use our trained analysts and artificial intelligence tools to look for FDA-approved drugs that might also have activity against a new target, such as the SARS-CoV-2 virus.” Might and team drilled right into core questions centering on severe COVID-19 symptoms: questions that could help guide and focus their attention and eventually a combination of technology, capability and intellect led them to the potential for androgen deprivation therapy and hence a highly potent degarelix.

Based on the Precision Medicine Institute’s initiative to identify existing FDA-approved candidates for COVID-19 patients, Director Light reports that the UAB team has identified over 200 compounds under ongoing investigation. These drugs exhibit the potential to “either block a target that has been identified in the COVID-19 pathway or manage a symptom of the disease.”

The Collaborative Network

Research and development collaborative networks represent a key element for innovation and progress, and this case is no exception. Upon the UAB Precision Medicine Institute findings, Matt Might immediately was on the phone communicating with those in his network that would be interested in such a discussion. As it turned out, David Goldstein, a colleague of his at Columbia University, had also come to the conclusion that androgen deprivation therapy represented a possible treatment pathway for at least certain severe to critical COVID-19 cases. And Might was also in touch with the VA’s head of research Dr. Rachel Ramoni to discuss the UAB findings.  An intelligent, directed and focused network was forming based on this early stage research.

The Hypothesis

Thanks to a rapid and responsive investigation into existing FDA-approved drugs, teams from both UAB and Columbia had come to the same conclusion that a powerful drug called degarelix could possibly help those patients hospitalized with COVID-19. Underlying their hypothesis was evidence suggesting that male hormones help the body produce TMPRSS2, a protein on the lung tissue. Their evidence points the reliance of COVID-19 on TMPRSS2 to enter the lung tissue and hence trigger a far more dangerous condition. Hence, the core hypothesis reported in UAB News: “By temporarily lowering male hormone levels, researchers believe they can reduce production of TMPRSS2 in lung tissue and thus prevent the virus from penetrating lung cells.”

Degarelix

Degarelix, made by Ferring Pharmaceuticals, has an immediate onset of action, binding to gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland and blocking their interaction with GnRH. This induces a fast and profound reduction in luteinizing hormone (LH), follicle-stimulating hormone (FSH) and in turn, testosterone suppression. The drug has been used to treat advanced cases of prostate cancer, and according to the VA, the drug “rapidly but temporarily suppresses the body’s production of make hormones. These hormones can fuel the growth of prostate cancer.”

The Study

That initial UAB to VA outreach in the research and development collaborative network ultimately led to a major clinical trial at the VA. Further research was used to reinforce the case for the VA to launch a clinical trial on May 15. A double-blind randomized controlled clinical trial investigating and comparing degarelix (Firmagon) to a placebo for improving the outcomes of 198 male COVID-19 patients, hospitalized in the acute care ward at the VA. The experimental drug arm includes the administration of one dose of the drug for a period of 28 days. This does include 2-prefilled syringes containing 3 ml of reconstituted degarelix concentrated to 40mg/ml plus the best supportive care associated with COVID-19 hospitalized cases.

The study team will investigate and compare to placebo whether this investigational drug plus best supportive care reduces the composite endpoint of mortality as well as the ongoing need for hospitalization or requirement for mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at Day 15 after randomization. Additional secondary outcome measures can be reviewed here. The study is planned to conclude in October 2020.

Research Sites

For this study targeting 198 patients, the VA, led by the West Los Angeles VA Medical Center, has mobilized a few sites including VA Centers in New York City (Manhattan and Brooklyn centers) as well as the VA Puget Sound.

Lead Research/Investigators

VA Greater Los Angeles Healthcare System, Los Angeles, CA

·         Matthew B. Rettig, MD 

·         Nicholas G Nickols, MD, PhD 

NYC Brooklyn Campus of the VA NY Harbor Healthcare System

·         Daniel Becker, MD 

·         Mohammad Al-Jam, MD 

NYC Manhattan Campus of the VA NY Harbor Healthcare System

·         Daniel Becker, MD

·         Tsay Jun-Chieh, MD 

VA Puget Sound Healthcare System, Seattle, WA

·         Bruce Montgomery, MD 

·         Elahe Mostaghel, MD 

Call to Action: Interested in the outcomes of this study? TrialSite News will publish results when they are made available. Sign up for the newsletter for daily updates. Commercial sponsors/pharma companies interested in UAB Hugh Kaul Precision Medicine Institute capabilities should contact them.

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