Safety profile of self-amplifying mRNA SARS-CoV-2 vaccine ARCT-154 in adults: a pooled phase 1/2/3 randomized clinical study.

BACKGROUND

Public health concerns due to ongoing emergence of SARS-CoV-2 variants necessitates further development of improved COVID-19 vaccines. One major innovation are self-amplifying mRNA vaccines, such as ARCT-154 (Arcturus Therapeutics, Inc.), which induces superior immunogenicity compared with conventional mRNA in terms of magnitude, breadth and persistence of neutralizing antibodies.

RESEARCH DESIGN AND

METHODS

In a pivotal placebo-controlled trial in Vietnam combining phase 1, 2 and 3 cohorts, over 17,000 adults received at least one dose of ARCT-154. Here, we report the safety and reactogenicity observations made.

RESULTS

ARCT-154 elicited more local reactions than the saline placebo, most reports of injection site pain were mild/moderate with only a few reporting severe pain. Most frequent solicited adverse events were fatigue, myalgia, headache, arthralgia and chills. Solicited local and systemic reactogenicity resolved within 7 days. Long-term follow-up has not revealed any safety concerns, with no reports of myocarditis or pericarditis. Acceptable tolerability of ARCT-154 was also observed in older participants and in those liable to severe consequences of COVID-19 due to underlying medical conditions. No serious consequences occurred in several pregnancies reported after vaccination, with normal outcomes when followed to term.

CONCLUSIONS

Data from this large trial suggest that ARCT-154 is safe and well tolerated.