Penn Medicine is participating in the safety and immunogenicity clinical trial for INO-4800, an investigational DNA vaccine developed by the biotechnology company INOVIO (Plymouth Meeting, PA) to prevent COVID-19 infection.
Phase I clinical testing of INO-4800 began immediately after the study was approved by the U.S. Food and Drug Administration (FDA) on April 6, with first dosing in up to 40 healthy volunteers beginning the same day. A second site, the Center for Pharmaceutical Research in Kansas City, MO, is also participating in the trial.
INO-4800 FDA Update
On November 16, 2020, INOVIO announced it had received clearance from the U.S. Food & Drug Administration (FDA) to proceed with the Phase 2 segment of its planned Phase 2/3 clinical trial for INO-4800. According to the company, the Phase 2 segment of the trial is designed to evaluate safety, tolerability and immunogenicity of INO-4800 in a 2-dose regimen (1.0 mg or 2.0 mg), in a three-to-one randomization to receive either INO-4800 or placebo for each dose to con rm the more appropriate dose(s) for each of three age groups with high risks of infection (18-50 years, 51-64 years and 65 years and older) for the subsequent Phase 3 efficacy evaluation.
The Phase 2 segment of the trial is expected to enroll approximately 400 participants at up to 17 U.S. sites to evaluate safety and immunogenicity in order to confirm the dose(s) for the subsequent efficacy evaluation planned for the Phase 3 segment.
The Phase 3 segment of the trial will enroll healthy men and non-pregnant women 18 years and older to evaluate the efficacy of the proposed dose(s) based on the data from the Phase 2 evaluation. Participants will be enrolled in a one-to-one randomization to receive either INO-4800 or a placebo. The primary endpoint of the Phase 3 segment will be virologically confirmed COVID-19 disease.
How Does the INO-4800 COVID-19 Vaccine Work?
According to vaccine developer Inovio (Plymouth Meeting, PA), INO-4800 is a DNA vaccine candidate matched to the novel coronavirus SARS-CoV-2, the cause of COVID-19 disease in humans. DNA vaccines are composed of optimized DNA plasmids, small units of double-stranded DNA synthesized or reorganized by computer sequencing technology designed to produce a specific immune response in the body.
INO-4800 is administered intradermally with a proprietary device, CELLECTRA 3PSP, designed by INOVIO to deliver optimized DNA into cells in the hope that these cells will be translated into proteins that generate a robust targeted T cell and antibody response to SARS-CoV-2. INOVIO claims that administration with the CELLECTRA device ensures that the DNA medicine is efficiently delivered directly into the body's cells, where it can go to work to drive an immune response.
INO-4800 Phase I: COVID-19 Vaccine Study Design
Each participant in the Phase I trial will receive two doses of INO-4800 four weeks apart. The initial immune responses and safety data from the study are expected by late summer. Preclinical data, which have been shared with global regulatory authorities and were submitted as part of the FDA submission, showed promising immune response results across multiple animal models.
In late June, interim data from INO-4800 suggested that 94% of Phase 1 trial participants demonstrated overall immune responses at Week 6 after two doses of INO-4800 in trial with 40 healthy volunteers in preliminary analyses. Additional preclinical trials, including challenge studies, continued in parallel with the Phase 1 clinical trial. Upon attaining initial safety and immunogenicity data from Phase 1 studies, INOVIO advanced INO-4800 to Phase 2 efficacy studies.
The Perelman School of Medicine is an INO-4800 Test Site
Pablo Tebas, MD, Director, Developmental Core, Penn Center for AIDS Research, and Director, Principal Investigator, AIDS Clinical Trial Unit (ACTU) research site, will lead the trial as principal investigator at the Perelman School of Medicine.
"We anticipate rapid enrollment of this initial study," Dr. Tebas said in a recent interview. “There has been tremendous interest in this vaccine among people who want to do what they can to help protect the greater public from this pandemic as soon as possible."
The global coalition of collaborators and partners assembled by INOVIO includes the scientific team at the Wistar Institute of the University of Pennsylvania, whose contributions included key research. INOVIO Pharmaceuticals received a $5 million grant from the Bill & Melinda Gates Foundation to accelerate the testing of the CELLECTRA 3PSP device to deliver the vaccine.