Inovio is enrolling 125 subjects in a second stage of its phase I trial of INO-4212 after generating positive initial safety and immune response data in the first set of 75 healthy volunteers.
The study will assess immune response characteristics generated with fewer intradermal administrations, lower doses, and with and without its DNA-based IL-12 immune activator.
The initial 75-subject stage of the trial evaluated INO-4212 in muscle and skin in five study arms in two and three doses, one including Inovio’s DNA-based IL-12 immune activator. In a study arm using intradermal administration, 100% (13/13) of subjects generated antigen-specific antibody responses after only two doses.
Similarly, in a study arm receiving the vaccine with intramuscular administration in combination with plasmid IL-12, 12 of 13 evaluable subjects (92%) demonstrated strong antibody responses after only two immunizations and 100% produced strong antibody responses after three immunizations. A majority of vaccinated subjects in each of the five cohorts produced strong Ebola antigen-specific T-cell responses.
Dr. J. Joseph Kim, Inovio’s President & CEO, said, “Immune responses from our Ebola vaccine in the first group of vaccine recipients met our highest expectations. Our aim is to pursue a regulatory approval path for Ebola using the Animal Rule, which relies on showing safety in humans and efficacy in multiple animal species.
"To pursue this path, apart from showing efficacy in animals we will require data supporting an optimal immunization regimen able to generate robust antigen specific immune responses in humans. Our goal now is to characterize the best immunization regimen and continue building the safety database required for regulatory approval.
“We plan to meet with regulators regarding a path forward following the close of this study early next year with results from 200 patients and positive preliminary pre-clinical data from several animal models, which we already have in hand.”
This expanded human study (CT.gov: NCT02464670) is being conducted by an Inovio-led consortium which was selected and awarded $45 million by the U.S. Defense Advanced Research Projects Agency (DARPA) in 2015 to take a multi-faceted approach to prevent and treat Ebola infection.
To date INO-4212 has been well tolerated and not demonstrated systemic serious adverse effects, such as fever, severe joint pain, and low white blood cell counts, reported in association with some viral vector based Ebola vaccines currently in development.
Moreover, unlike viral vectored vaccines, which must be kept frozen, INO-4212 was formulated in a refrigerated solution (2-8 C).
Under this DARPA-funded program, Inovio and its collaborators are developing multiple approaches against Ebola. This program allows for the development and early clinical testing of:
Inovio's DNA-based vaccine INO-4212 against Ebola.
Inovio's therapeutic Ebola dMAb product. This new technology has properties complementary to Inovio’s Ebola DNA vaccine to potentially protect against Ebola. For example, while a DNA vaccine may provide longer lasting protection, an Ebola dMAb product may provide more rapid therapeutic benefit (as shown in Inovio’s Chikungunya and dengue programs); and
A highly potent conventional protein-based therapeutic monoclonal antibody (mAb) product against Ebola virus infection, co-developed with MedImmune, the global biologics research & development arm of AstraZeneca.