INOVIO (NASDAQ:INO), a biotechnology company focused on bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases, cancer, and HPV-associated diseases, today announced positive safety, tolerability and immunogenicity data from its placebo-controlled and blinded Phase 2 segment of its Phase 2/3 clinical trial in the U.S., called INNOVATE (INOVIO INO-4800 Vaccine Trial for Efficacy), evaluating INO-4800, its DNA vaccine candidate for COVID-19. Preliminary results show in a larger population that INO-4800 was generally safe, well-tolerated and immunogenic in all studied age groups.
Findings from the Phase 2 Clinical Trial:
- The Phase 2 segment of the trial enrolled approximately 400 participants, 18 years of age or older, at 16 U.S. sites.
- Participants received either INO-4800 (1.0 mg or 2.0 mg dose) or placebo at 0 and 4 weeks (randomized 3:3:1:1). Each dose was administered by intradermal injection followed by electroporation using INOVIO's CELLECTRA®, its proprietary smart device.
- Safety endpoints included systemic and local administration site reactions through 8 weeks post-dose one (or 4 weeks post-dose 2). Immunology endpoints included antigen-specific binding antibody titers, neutralization titers, and antigen-specific interferon-gamma (IFN-γ) cellular immune responses after two doses of the vaccine.
- Vaccine administration was generally safe and well-tolerated. The majority of adverse events (AEs) were Grade 1 and Grade 2 in severity and did not appear to increase in frequency with the second dose. The number of participants experiencing each of the most common AEs did not differ between the two dosing groups.
- The geometric mean fold rise (GMFR) of binding and neutralizing antibody levels were statistically significantly greater in the 2.0 mg dose group versus the 1.0 mg dose group.
- The T cell immune responses measured by the ELISpot assay were also higher in the 2.0 mg dose group compared to the 1.0 mg dose group.
- ClinicalTrials.gov identifier: NCT04642638
The Phase 2 segment of INNOVATE was designed to evaluate the safety, tolerability and immunogenicity of INO-4800 in a two-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 identify optimal dose(s) for two age groups (18-50 years and 51 years and older) for the subsequent Phase 3 efficacy evaluation. The preliminary Phase 2 results showed that INO-4800 was safe, well-tolerated and immunogenic in all tested age groups. The trial was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, (JPEO-CBRND) in coordination with the Office of the Assistant Secretary of Defense for Health Affairs (OASD(HA)) and the Defense Health Agency. Results from the trial can be found in the paper entitled "Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A Preliminary Report of a Randomized, Blinded, Placebo-controlled, Phase 2 Clinical Trial in Adults at High Risk of Viral Exposure," has been published as a pre-print in MedRxiv (https://doi.org/10.1101/2021.05.07.21256652) prior to peer review.
Dr. Laurent M. Humeau, INOVIO's Chief Scientific Officer, said, "We thank the volunteers who are participating in our INNOVATE Phase 2 blinded trial, as well as the research partners, clinical teams and INOVIO employees who have been working tirelessly to advance this important work. Our Phase 2 results validate our initial COVID-19 Phase 1 results in a larger population, which show that INO-4800 continues to be generally safe, well-tolerated and immunogenic in all studied age groups. The expanded data set enabled a clear dose selection to be made with 2.0 mg as the dose for the global Phase 3 efficacy trial."
INOVIO plans to file preliminary Phase 2 results and device data with the U.S. Food and Drug Administration (FDA). Following the submission and FDA concurrence to proceed, the company plans to conduct a global Phase 3 clinical trial for INO-4800. The company recognizes the growing and unmet global demand for both initial as well as boosting doses of COVID-19 vaccines and looks forward to supporting the rollout of much needed additional vaccines to prevent the spread of COVID-19 – including both current and future variants – around the world.
About the INO-4800 "INNOVATE" Phase 2/3 Clinical Trial
The lead Principal Investigator for the Phase 2 segment of INNOVATE is Dr. Pablo Tebas, Professor of Medicine at the Hospital of the University of Pennsylvania. The Phase 2 clinical 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, to confirm the more appropriate dosing level for each of three age groups (18-50 years, 51-64 years and 65 years and older) for the subsequent Phase 3 efficacy evaluation.
The Phase 3 segment of the INNOVATE trial in the U.S. remains on partial clinical hold until INOVIO satisfactorily resolves the FDA's remaining questions related to the CELLECTRA® 2000 device that will be used to deliver INO-4800 into the cells of the skin. The company plans to satisfy the remaining device questions during the Phase 2 segment and prior to the start of the Phase 3 segment of INNOVATE. In the Phase 3 segment of the trial, INOVIO intends to enroll men and non-pregnant women 18 years and older, to evaluate the efficacy of the proposed dosing level(s) for each age group based on the data from the Phase 2 evaluation. The trial will predominately be conducted globally; participants will be enrolled in a two-to-one randomization to receive either INO-4800 or a placebo. The Phase 3 segment will be case-driven with the final number of enrollees to be determined by the incidence of COVID-19 during the Phase 3 segment. The primary endpoint of the Phase 3 segment will be virologically-confirmed COVID-19 disease.
INO-4800 is INOVIO's DNA vaccine candidate against SARS-CoV-2, the novel coronavirus that causes COVID-19. INOVIO has extensive experience working with coronaviruses and was the first company to initiate a Phase 2a trial for INO-4700, a DNA vaccine candidate for a related coronavirus that causes Middle East Respiratory Syndrome (MERS).
Composed of an optimized DNA plasmid, INO-4800 is delivered directly into cells in the body via a proprietary smart device to produce a robust, safe and tolerable immune response. INO-4800 is the only nucleic-acid based vaccine that is stable at room temperature for more than a year, at 37oC for more than a month, has a five-year projected shelf life at normal refrigeration temperature and does not need to be frozen during transport or storage – all of which are important considerations when preparing for mass immunizations.