Closer to the border in the Southern Texas town of Edinburg, a prominent trial site organization serves the local community, bringing a range of therapies to those in need, some advanced and novel, others for repurposed investigation. In the age of COVID-19, research has never been more important to local communities, from offering access to what could be life saving therapies and vaccines to providing standard of care alongside the research for what is in many cases underserved populations. A non-profit 501(c)3 organization, DHR Health Institute of Research and Development, is on a mission to enhance translational and clinical research in critical areas of need through collaboration with internal investigators and other affiliated academic and non-academic partners. This part of the United States, known as the Rio Grande Valley region, includes a population of about 1.4 million of which over 90% are Hispanic. Profiled in the past by TrialSite, this trial site is conducting COVID-19 clinical trials testing a number of novel and repurposed drugs including an oral medication called Camostat mesilate.
What is Camostat Mesilate?
Camostat Mesilate is a new potential therapy for COVID-19. Approved in Japan for pancreatitis and postoperative reflux esophagitis that inhibits a protease enzyme. It so happens to be the same protease that assists SARS-CoV-2 in binding to human cells using the ACE2 receptor. The drug is manufactured by Ono Pharmaceutical and in the United States is licensed by Sagent Pharmaceuticals, a Nichi-Iko Group Company from Japan.
Why is this drug relevant?
SARS-CoV-2 exploits the cell entry receptor protein angiotensin converting enzyme II (ACE-2) to access and infect human cells. The interaction between ACE2 and the coronavirus spike protein isn’t the active site. Rather, this process necessitates the serine protease TMPRSS2.
TMPRSS2 is a serine protease that primes the spike protein of highly pathogenic human coronavirus, such as SARS-CoV and MERS-CoV and facilitates its entry into the host human cell.
Camostat mesilate is a potent serine protease inhibitor. Research has demonstrated that SARS-CoV-2 cellular entry can be blocked by camostat mesilate. In mice for example, dosed concentrations similar to those dosages relevant for humans, researchers found reduced mortality following SARS-CoV-2 infection from 100% to 30-35%.
Numerous research reports make the case that SARS-CoV-2 can use TMPRSS2 and closely related proteases for infection in the upper respiratory tract and that this spread in the human lung can be inhibited or blocked by Camostat mesilate and its metabolite GBPA.
How many clinical trials targeting COVID-19 use this drug?
Based on a search of Clinicaltrials.gov, a total of 25 studies are disclosed.
Note another major study, sponsored by Sagent Pharmaceuticals is the CAMELOT study (NCT04583592). Announced during November 2020, the Phase 2 clinical trial targets high risk COVID-19 outpatients at over 20 trial site locations.
The ACTIV-2 Study Program
Sponsored by the National Institutes of Health (NIH) and others, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) includes a number of studies including the ACTIV-2 master protocol, a Phase 2 trial that can seamlessly expand to Phase 3. These studies emphasize therapeutics for those infected with COVID-19 who are not hospitalized with an aim to evaluate safety and to investigate a variety of therapies, including Camostat mesilate.
The Camostat mesilate study (NCT04518410) study is sponsored by Sagent Pharmaceuticals. The Camostat arm includes treatment of 200mg (2×100 mg) film-coated tablets administered orally every 6 hours for 7 days.
The Search for a Treatment
Dr. Sohail Rao heads DHR Health Institute for Research and Development and commented recently in the local media that unfortunately a year after the onset of the pandemic and the majority of the available treatments for COVID-19 involve emergency treatment.
Now investigators are pursuing earlier stage care. So that when an individual is diagnosed with COVID-19, they are not just sent home and told to rest and watch for worsening symptoms. This is unfortunately how many people’s condition worsened, and by the time they return to the hospital with worsening conditions in some cases, it was too late.
Dr. Rao shared, “We have not yet found an absolute treatment for COVID-19.” But perhaps this study drug could be such a treatment?
The Study Participation
This study is open for those living in the Rio Grande Valley region that have tested positive for COVID-19 via PCR or rapid antigen test and within 8 days of symptom onset. Patients receive the study drug for seven days and are closely monitored for 28 days after commencement of the treatment.
The study includes a digital diary via smartphone app so patients can provide feedback to the investigators and study team right from the comfort of their home. Dr. Rao reports, “You will daily record some of your symptoms and signs in that particular app.” Moreover, the study team’s nurse will call the participant every two to three days. Participants also receive $75 per day.
Call to Action: For those in the Rio Grande Valley area that have a loved one recently infected with COVID-19, consider this particular study, part of the ACTIV-2 program sponsored by the National Institutes of Health. Contact DHR Research here.