Phase I Interim Results of a Phase I/II Study of the IgG-Fc Fusion COVID-19 Subunit Vaccine, AKS-452

Abstract

Background: To address the coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recombinant subunit vaccine, AKS-452, is being developed comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain (SP/RBD) antigen and human IgG1 Fc emulsified in the water-in-oil adjuvant, Montanide™ ISA 720.Methods: A single-center, open-label, phase I dose-finding and safety study was conducted with 60 healthy adults (18 – 65 years) receiving one or two doses 28 days apart of 22.5 µg, 45 µg, or 90 µg of AKS-452 (i.e., six cohorts, N=10 subjects per cohort). Primary endpoints were safety and reactogenicity and secondary endpoints were immunogenicity assessments.Findings: No AEs ≥ 3, no SAEs attributable to AKS-452, and no SARS-CoV-2 viral infections occurred during the study. Seroconversion rates of anti-SARS-CoV-2 SP/RBD IgG titers in the 22.5, 45, and 90 µg cohorts at day 28 were 70%, 90%, and 100%, respectively, which all increased to 100% at day 56 (except 89% for the single-dose 22.5 µg cohort). All IgG titers were Th1-isotype skewed and efficiently bound mutant SP/RBD from several SARS-CoV-2 variants with strong neutralization potencies of live virus infection of cells (including alpha and delta variants). Interpretation: The favorable safety and immunogenicity profiles of this phase I study (ClinicalTrials.gov: NCT04681092) support phase II initiation of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain. Clinical Trial Registration Details: ClinicalTrials.gov: NCT04681092.Funding Information: This research was not funded by any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Declaration of Interests: The following authors declare the following financial interests/personal relationships which may be considered as potential competing interests: the following authors were employed by and received monetary compensation from Akston Biosciences, Inc.: DGA, ARD,MMS, SM, RR, EKG, TS, SK, JRH, NJS, VR, SN, TML, TZ. No other authors were personally compensated by Akston Biosciences.Ethics Approval Statement: The trial was reviewed and approved by the Central Committee on esearch involving Humans in The Hague, together with a marginal review by the competent authority (Ministry of Health, Welfare and Sport (VWS)). Local feasibility was assessed and approved by the UMCG Institutional Review Board. An informed consent form was signed voluntarily before any study-related procedure was performed, indicating that the subject understood the purpose and procedures required for the study and was willing to participate.