Washington University School of Medicine in St. Louis (WUSM St. Louis) investigators are now preparing for a critically important Phase 3 clinical trial to test a medicine for patients with mild symptoms in the early course of COVID-19 treatment. Called the “STOP COVID Trial 2,” this “contactless” or remote study means that volunteers may participate without leaving their home. The investigational team supplies the medication, known as fluvoxamine, delivered via courier, or shipped overnight. The fundamental study question: does fluvoxamine help to stop the worsening of symptoms associated with COVID-19, hence preventing hospitalization? This is a timely research program. The first trial in this program, the “Stop COVID-Trial,” showed positive results. So much so that the program’s sponsor, a wealthy entrepreneur, and philanthropist named Steve Kirsch, founder of the COVID-19 Early Treatment Fund (CETF), continues to invest in critically important research investigating the efficacy early course COVID-19 FDA approved repurposed treatments, such as fluvoxamine. Mr. Kirsch, founder of several successful companies, is doing the nation and the world a favor by putting lots of his own money, time, and brain power into trying to find early course COVID-19 treatments. This should have been the responsibility of the National Institutes of Health (NIH) and its National Institute of Allergies and Infectious Diseases (NIAID) led by the widely acclaimed and wildly popular Dr. Anthony Fauci. Instead of even allocating minute investments into any economical drug repurposing initiative, the nation’s research agency apparatus—NIH (NIAID, et al) and associated federal agencies such as BARDA, part of HHS, along with Operation Warp Speed via the federal gatekeeper of all COVID-19 research funding—ACTIV (Accelerating COVID-19 Therapeutic Interventions & Vaccines), have opted to invest well over $12.5 billion overwhelmingly focusing on vaccines and expensive novel monoclonal antibodies. While the rush for a vaccine is needed and understood, why was so much attention placed on opting not to focus on the potential of existing FDA-approved, economical and pragmatic repurposed drugs for early course COVID-19 cases? This latter Phase 3 remote trial targets up to 1,100 participants and starts this month and runs through till July 2021.
TrialSite provides a brief breakdown of the investigations into fluvoxamine out of WUSM St. Louis.
The Target Repurposed Product
In the “STOP COVID Trial,” WUSM St. Louis seeks to investigate the repurposing of an approved FDA drug known as fluvoxamine. An antidepressant drug approved by the FDA for obsessive-compulsive disorder, the use of this drug for addressing early onset COVID-19 makes it investigational, meaning it is not approved by the FDA for this use.
Known in the market as Luvox, the serotonin reuptake inhibitor (SSRI) class drug is used in the United States for OCD and social anxiety disorder. In some nations (such as Australia, UK and Russia) this drug is prescribed for depression. Indicated for children and adolescents with OCD, it is reported to act long term, retaining its therapeutic efficacy for at least a year. With treatment as low as $20, the drug is not only economical but widely available. The FDA label is included here.
The drug was originally developed by a unit of Solvay Pharmaceuticals in Belgium and first approved in the U.S. by the FDA in 1994 as Luvox.
During the pandemic, a number of drug repurposing initiatives were launched to explore the efficacy targeting SARS-CoV-2, the virus behind COVID-19. However, as TrialSite has chronicled, not early enough. For example, mounting evidence for the antiparasitic drug ivermectin have attracted little attention among the medical-industry-government complex. Why? Probably because there is little economic incentive for sponsors’ involvement.
But there have been a number of little publicized initiatives. Although the federal research apparatus did look at high end IL6 inhibitors, which failed, other privately-funded groups looked to drugs such as fluvoxamine.
With pandemic conditions worsening by April, various groups sprung into motion, such as the COVID-19 Early Treatment Fund (CETF)—more on that below. By Novembe,r the Journal of the American Medical Association published the ongoing results of a 152 person study, funded by CETF, revealing that Fluvoxamine evidences material promise in treating serious breathing difficulties associated with COVID-19.
The COVID-19 Early Treatment Fund (CETF) announced the publishing of the WUSM St Louis double-blind, randomized controlled clinical trial that investigated the potential of fluvoxamine if taken within seven days of first symptoms of COVID-19 can reduce the risk of respiratory degradation. This CETF-funded study revealed that fluvoxamine was in fact effective. None of the 80 participants who took the drug met the respiratory deterioration criteria compared to an 8.3% rate in the 72 patients who took a placebo.
Private Funding Sources Cover the Government Gap
As TrialSite has chronicled, over $12.5 billion of taxpayer money alone has gone into just a handful of vaccine and novel monoclonal antibody development efforts thanks to the choices of the NIH Foundation’s ACTIV—the entity established to prioritize what treatments and therapies receive federal funding. TrialSite introduced the NIH’s ACTIV of federal government, pharma industry and academic center centralizing bias over the needs and demands of the clinic, that is health systems, hospitals and regional and community health operations that care for America’s population.
TrialSite news suggested that wasn’t a surprise given the powerful interests vested in the more expensive vaccine and advanced novel therapy development approaches supported by the NIH, NIAID, HHS, and others. TrialSite’s position has been that investment in all are necessary—that is, the vaccine and more advanced drugs as well as appropriate government support for low cost, repurposed targets. A free market requires a plethora of choices if available. A pandemic market demands them now.
But given the aforementioned government and industry and select academic bias, pragmatic approaches to early onset treatment for COVID-19 with more economical and readily available, repurposed drug candidates would require a different source of capital than U.S. taxpayer money via NIH and peer agencies.
CETF was created to ensure rapid and successful completion of outpatient clinical trials for effective early treatments for COVID-19, using existing drugs. Taking a bold approach in a bid to offer the shortest path to saving lives, this group has received little media attention.
While the pandemic began its deadly rage, the serial entrepreneur, one who founded several companies such as Mouse Systems, Frame Technology Corp, Infoseek and others, put his regular business in the hands of his co-founder so he could dedicate himself to finding an early stage treatment to COVID-19. Consulting with industry and medical experts, he quickly realized that the fastest, most effective way to reduce fatalities was by leveraging existing drugs to treat patients at the onset of the infection.
Mr. Kirsch identified early on what TrialSite has been writing about for months: that there was a dangerous and deadly gap in focus on early onset treatment for COVID-19, hence this led the entrepreneur to allocate funds to launch CETF.
With a powerful list of scientific advisors, CETF may be on to something with the STOP COVID trials.
The Breakthrough Study
The STOP COVID Trial (NCT04342663) started back in April and involves an investigation to determine if fluvoxamine can be used in early course of the COVID-19 infection to prevent more serious complications such as shortness of breath.
Led by Dr. Eric Lenze, director of the Healthy Mind Lab at Washington University School of Medicine in St Louis, the team found that fluvoxamine has strong anti-inflammatory properties. Testing this hypothesis, the St. Louis-based team asked if these properties could contribute to stop deadly cytokine storms, the body’s massive, sometimes deadly, inflammatory reactions to COVID-19
Much to the delight of the study team, they discovered they were on to something big as in this home-based, remote trial involving 80 participants absolutely no one who took fluvoxamine hit the endpoint of clinical deterioration (oxygen saturation of 92% or lower along with difficulty breathing or hospitalization for pneumonia), as opposed to six of the 72 people who got the placebo and experienced deterioration.
The results evidence that fluvoxamine has the potential to reduce the risk of hospitalization in COVID-19 patients—a critical milestone.
‘STOP COVID 2’ Study
Now the WUSM St. Louis team gears up for the much larger Phase 3 “STOP COVID 2” clinical trial (NCT04668950). Targeting 1,100 participants in partnership again with CETF and led by Principal Investigator Dr. Lenze, the study team seeks to determine if fluvoxamine can be used early in the course of the COVID-19 infection to prevent more serious complications, such as shortness of breath.
Like the last study, this is a fully remote trial, meaning there is no face-to-face contact; study materials including the study drug will be shipped to participants’ houses and the study is available to residents in the United States and Canada.
Officially titled “Fluvoxamine for Early Treatment of COVID—19: a Fully-remote, Randomized Placebo Controlled Trial,” the study starts this month (December) and runs until July 2021.
In addition to Washington University School of Medicine St. Louis, the lead trial site center, other participating centers in this remote study include the following:
· Northwestern University, Evanston, IL
· University of Utah, Salt Lake City, UT
· Fred Hutchinson, Seattle, WA
· McGill University Health Center, Montreal, Canada
Eric Lenze, MD, Wallace and Lucille K. Renard Professor of Psychiatry