Worldwide, over 125 COVID-19 vaccines are now in development, while only a handful have progressed to human clinical trials. Of those vaccines currently undergoing clinical trials, Inovio Pharmaceuticals started recruiting patients in April 2020 to test the INO-4800 experimental vaccine. Study sites include Central Kentucky Research Associates, Center for Pharmaceutical Research, and the University of Philadelphia. Volunteering participants represent the absolute key, at this point, along with the science of the particular vaccine, to the eventual success or not of INO-4800: will the vaccine work? Recently, a local Pennsylvania news outlet highlighted one of the volunteers, a 41-year-old Manheim Township PA mother, revealing a little more about this particularly important trial.
Stella Sexton recalls responding to the call for volunteers on the Penn Medicine Lancaster General Health website. A humanitarian impulse perhaps as Sexton isn’t currently a stay-at-home mom, is healthy, and thought she could contribute and give back, reports Jeff Hawkes of Lancaster Online.
Patient Participation: The Biggest Challenge in Clinical Trials
Stella Sexton has served the society by stepping up to become a participant in a clinical trial testing a COVID-19 experimental vaccine candidate. Medical progress itself is premised on advancing evidence, and this must be produced via the scientific method as manifested in properly designed random controlled trials. That human volunteers are an instrumental variable in the success formula cannot be understated. Medical progress itself is premised upon human participation in clinical research.
One of the primary causes of clinical trial failure is the lack of patient participation. From the industry lens, it would be considered “the patient recruitment problem.”
Yes, more often than not, clinical trials fail due to the lack of participants. While 25% of cancer trials fail to enroll sufficient numbers of patients, 86% of clinical trials fail to reach recruitment targets with their specific time periods.
The Health System is a Good Way to Find Participants
The research center, University of Pennsylvania, runs Penn Medicine, a major multi-hospital health system based in Philadelphia, PA. Back in 2015, one of Pennsylvania’s top five health systems, Lancaster General Health, joined Penn Medicine, forming a formidable health system in the region. Residing over an hour west of Philadelphia in rural Lancaster County, this critically important clinical trial ultimately found this particular volunteer via health system consolidation. That expands the coverage and total number of potential patients/volunteers. In this case, Stella Sexton noticed the vaccine study on the system’s website, which is localized to her area.
A Key Milestone: Signed Informed Consent
Unless there are emergency exceptions, every clinical trial requires informed consent. In this case, the volunteer read and signed a 22-page informed consent document. This can be considered a kind of sacred process in a clinical trial. The informed consent document should be authored in such a way that the participant can truly understand what the study is about; the goals, and importantly, the risks of the process including any specific study drug risks.
In the case of INO-4800, any risks are explained even if just “theoretical” such as that the vaccine could possibly make the participant more susceptible to COVID-19. This kind of risk can occur as TrialSite News reported on one such incident in the Philippines with a Sanofi Pasteur dengue fever vaccine that resulted in fatalities.
The Study Overview
That the investigational vaccine has made it to this point is impressed—many drugs and vaccines don’t progress past animal research. However, INO-4800 evidence has been well-tolerated first in preclinical studies in mice, and then in the first cohort of 40 participants in the Phase I stage of the study.
This Phase I open-label study is designed to evaluate the safety, tolerability, and immunogenicity of INO-4800, the prophylactic vaccine against SARS-CoV-2 which is administered intradermally followed by electroporation. Dr. Pablo Tebas, Principal Investigator and Director of the HIV Clinical Trials Unit at Penn, leads the University of Pennsylvania study.
The Experimental Vaccine
In the case of INO-4800, the experimental vaccine is delivered into the dermis, or the skin layer underneath the epidermis (the upper skin layer). A DNA vaccine candidate matched to SARS-CoV-2 virus, the vaccine’s DNA cells are essentially driven into the cells of the study participant via a proprietary platform hand-held smart device called CELLECTRA.® The participant, in this case Mrs. Sexton, needs not worry about viral infection or passing it to her family as the INO-4800 basis is a snippet of the virus’ DNA and not the virus itself.
So INO-4800 delivers optimized DNA plasmids directly into cells in a quest to trigger an antibody response, actually turning the body into medicine. Put another way, INO-4800 contains the DNA for the spike protein, which is on the surface of the novel coronavirus (SARS-CoV-2). If these plasmids come into the body successfully, the spike protein will be expressed in the cells of the individual receiving the vaccine, triggering the human immune system reaction. In theory, once this occurs, the immune system stops COVID-19.
According to experts such as Dr. David Weiner of the Wistar Institute, a collaborator with Inovio Pharmaceuticals, DNA-based vaccines such as INO-4800 has a number of advantages from safety profile to the relative ease of manufacturing and production. The INO-4800 experimental vaccine delivery does require the use of a smart device called CELLECTRA. The device uses a brief electrical pulse to open small pores in the cell, reversibly facilitating the movement of the plasmids into the cell.
The Real Heroes
Thanks to Stella Sexton for standing up and stepping into the Phase I INO-4800 clinical trial. But for participants such as Mrs. Sexton, no vaccine will progress to the next Phase and hopefully to the finish line: U.S. Food and Drug Administration (FDA) approval. Lancaster Online reported that she happens to have “humanitarian impulse” that has driven her to help in other ways, such as giving blood. In an age where mass media promotes a winner-takes-all culture of billionaires, sports stars to celebrities, the real heroes are people like Sexton.
Serving the INO-4800 study for the University of Pennsylvania is Dr. Pablo Tebas, Principal Investigator and Director of the HIV clinical trials unit. Dr. Tebas is also a co-founder/member of the HIV Reservoirs and Viral Eradication (CURE) Transformative Science Group (TSH) of the AIDS clinical trials group. He is a prominent principal investigator and key opinion leader.
Call to Action: Do you live in the Philadelphia metropolitan area and fit the inclusion criteria for the vaccine study? Consider participating.