Inovio has announced positive interim clinical data of INO 4800 vaccine candidate against novel coronavirus (SARS-CoV-2), from the first two Phase I clinical trial cohorts. In addition, INO 4800 has been selected to participate in a non-human primate (NHP) challenge study as part of the U.S. government’s Operation Warp Speed, a new national program aiming to provide substantial quantities of safe, effective vaccine by January 2021. Furthermore, Inovio has expanded its Phase I trial to add older participants in additional cohorts and plans to initiate a Phase II/III efficacy trial this summer upon regulatory concurrence.
The Phase I clinical trial of INO 4800 initially enrolled 40 healthy adult volunteers 18 to 50 years of age at two U.S. sites with funding from the Coalition for Epidemic Preparedness Innovations (CEPI). The participants were enrolled into 1.0 mg and 2.0 mg dose cohorts; each participant received two doses of INO 4800 four weeks apart. Each dose was administered by intradermal injection using Inovio’s CELLECTRA 2000 device. An independent Data Safety Monitoring Board reviewed the safety data. INO 4800 was generally safe and well-tolerated in all participants in both cohorts through week 8; all ten reported adverse events (AEs) were grade 1 in severity, and most were local injection site redness. There were no reported serious adverse events (SAEs).
Multiple immunology assays including those for humoral and cellular immune responses are being conducted for both 1.0 mg and 2.0 mg dose cohorts after two doses at week 6. Analyses to date have shown that 94% (34 out of 36 total trial participants) demonstrated overall immunological response rates based on preliminary data assessing humoral (binding and neutralizing) and T cell immune responses. One participant in the 1.0 mg dose cohort and two participants in the 2.0 mg dose cohort were excluded in the immune analyses as they tested positive for COVID-19 immune responses at study entry, indicating prior infection. One participant in the 2.0 mg dose cohort discontinued the study for reasons unrelated to safety or tolerability. Inovio plans to publish the full data set in a peer-reviewed medical journal.
One key feature of Inovio’s DNA vaccines is the ability to generate balanced antibody and T cell immune responses, which in the case of SARS-CoV-2 infection could be important in the development of potential COVID-19 vaccines. In this regard, recent scientific reports have highlighted that SARS-CoV-2-specific T cells found in convalescent patients have been positively implicated in controlling the severity of their COVID-19 disease (Grifoni et al, Cell 2020) while other studies have shown that a significant proportion (33% to 40%) of convalescent individuals in their reports had neutralizing antibody below detectable levels (Robbiani et al, Nature 2020 and Payne et al, MMWR 2020). In addition to positive interim Phase I data, INO 4800 has been shown to protect mice in SARS-CoV-2 viral challenge studies, where vaccination with INO 4800 prevented viral replication in the lungs of animals challenged with SARS-CoV-2. Moreover, INO-4800 is currently being tested in a ferret challenge model as well as in NHP challenge studies as part of Operation Warp Speed.