A phase 1/2 randomized, double-blinded, placebo controlled ascending dose trial to assess the safety, tolerability and immunogenicity of ARCT-021 in healthy adults
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Background: The pandemic of coronavirus disease-19 (Covid-19) continues to afflict the lives and livelihoods of many as global demand for vaccine supply remains unmet. Methods: Phase 1 of this trial (N=42) assessed the safety, tolerability and immunogenicity of ascending levels of one-dose ARCT-021, a self-amplifying mRNA vaccine against Covid-19. Phase 2 (N=64) tested two-doses of ARCT-021 given 28 days apart. Both young and older adults were enrolled. The primary safety outcomes were local and systemic solicited adverse events (AEs) reported immediately and up to 7 days post-inoculation and unsolicited events reported up to 56 days after inoculation. Secondary and exploratory outcomes were antibody and T cell responses to vaccination, respectively. Results: ARCT-021 was well tolerated up to one 7.5 μg dose and two 5.0 μg doses. Local solicited AEs, namely injection-site pain and tenderness, as well as systemic solicited AEs, such as fatigue, headache and myalgia, were more common in ARCT-021 than placebo recipients, and in younger than older adults. Seroconversion rate for anti-S IgG was 100% in all cohorts except for the 1 μg one-dose in younger adults and the 7.5 μg one-dose in older adults, which were each 80%. Neutralizing antibody titers increased with increasing dose although the responses following 5.0 μg and 7.5 μg ARCT-021 were similar. Anti-S IgG titers overlapped with those in Covid-19 convalescent plasma. ARCT-021 also elicited T-cell responses against the S glycoprotein. Conclusion: Taken collectively, the favorable safety and immunogenicity profiles support further clinical development of ARCT-021.
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Phase I/II clinical trials of ARCT-021 indicated production of robust anti-spike specific antibodies when 5.0-7.5 μg was administered per dose group, but it failed to reach 100% seroconversion rate.
“the results of phase I/II clinical trials of the saRNA vaccine ARCT-021 developed by Arcturus Therapeutics indicated the production of robust anti-spike specific antibodies when 5.0–7.5 μg was administered per dose group, but it also failed to reach 100% seroconversion rate.441,442”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [442]
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- Authors
- Low, J. G., de Alwis, R., Chen, S., Kalimuddin, S., Leong, Y. S., Mah, T. K. L., Yuen, N., Tan, H. C., Zhang, S. L., Sim, J. X. Y., Chan, Y. F. Z., Syenina, A., Yee, J. X., Ong, E. Z., Sekulovich, R., Sullivan, B. B., Lindert, K., Sullivan, S. B., Chivukula, P., Hughes, S. G., & Ooi, E. E.
- Affiliations
- National University of Singapore (SG)
- Singapore General Hospital (SG)
- Arcturus Therapeutics (United States) (US)
- Corresponding author
- Hughes, Steven G.
- ORCID
- Venue
- medRxiv
- Publisher
- openRxiv
- Published
- 2021-07-02
- OpenAlex
- W3176098528
- Cited by
- 19
- References
- 27
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 11 · 2021: 2
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Locations
- medRxiv (acceptedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- self-amplifying mRNA vaccine, COVID-19 vaccines, SARS-CoV-2 spike protein, vaccine safety, immunogenicity, dose escalation, neutralizing antibodies, T cell response, adverse events, older adults, seroconversion
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