ARCT-154-01: A Large Scale Clinical Trial Marking a Milestone for Next-Generation sa-mRNA Vaccines

The ARCT-154-01 clinical trial (NCT05012943), conducted in Vietnam by Vinbiocare Biotechnology Joint Stock Company (a member of Vingroup), has generated globally valuable scientific data for self-amplifying mRNA (sa-mRNA) vaccine technology. ARCT-154 was specifically designed to target the spike protein of SARS-CoV-2 – the key component enabling the virus to enter human cells.

The sa-mRNA vaccine represents an advanced generation of mRNA technology. After administration, it is capable of self replication within cells, producing higher levels of antigen with lower doses. This mechanism induces a strong and durable immune response. Beyond enhancing protective efficacy, the technology also holds promise for reducing manufacturing costs and expanding applications in the prevention of infectious diseases.

With more than 19,000 Vietnamese volunteers enrolled, ARCT-154-01 is one of the largest global clinical trials of a preventive sa-mRNA COVID-19 vaccine, integrating all three clinical phases (1/2/3). The collected data demonstrated:

• High protective efficacy: Two doses of ARCT-154 achieved 56.6% efficacy against overall COVID-19 and 95.3% efficacy against severe COVID-19, primarily during the period when the Delta variant was predominant (1).

• Robust immune response: 94.1% of vaccinated participants achieved seroconversion with neutralizing antibodies (1). Clinical data generated in Vietnam provided the foundation for a Phase 3 trial conducted in Japan (jRCT 2071220080), where an ARCT-154 booster dose induced higher antibody levels than the Pfizer vaccine, despite using a lower dose (2).

• Safety profile: Preliminary results indicated that the vaccine was well tolerated, with most adverse events being mild to moderate in severity (1).

With these promising outcomes, ARCT-154 (trade name Kostaive™) became the first preventive sa-mRNA COVID-19 vaccine to receive marketing authorization in Japan (November 2023) and in the European Union (February 2025) (3,4).

(Source: Meiji Seika Pharma)

The success of ARCT-154-01 not only demonstrated the efficacy and safety of the sa-mRNA vaccine, but also laid the foundation for a new generation of vaccines capable of inducing strong immunity at lower doses with optimized costs. Clinical data generated in Vietnam have become an important scientific basis for subsequent sa-mRNA vaccine research in COVID-19 prevention, including improved formulations and booster doses targeting emerging variants (2,5). The approval of Kostaive™ has opened new prospects for the application of sa-mRNA technology in the prevention of other infectious diseases (such as seasonal influenza, respiratory syncytial virus [RSV], and herpes), as well as potential future applications in cancer therapeutics (6).

These achievements affirm the capability of Vinmec–VinUni to manage and implement complex, large-scale clinical trials in accordance with international standards, creating opportunities for expanded collaboration with domestic and international partners in this field.

References

1. Hồ NT, Hughes SG, Ta VT, Phan LT, Đỗ Q, Nguyễn TV, et al. Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials. Nature Communications. 2024 May 14;15(1):4081. Available from: https://www.nature.com/articles/s41467-024-47905-1
2. Oda Y, Kumagai Y, Kanai M, Iwama Y, Okura I, Minamida T, et al. Immunogenicity and safety of a booster dose of a self-amplifying RNA COVID-19 vaccine (ARCT-154) versus BNT162b2 mRNA COVID-19 vaccine: a double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial. The Lancet Infectious Diseases [Internet]. 2023 Dec 20;24(4):351–60. Available from: https://pubmed.ncbi.nlm.nih.gov/38141632/
3. Arcturus, 2023. Japan’s Ministry of Health, Labour and Welfare Approves CSL and Arcturus Therapeutics’ ARCT-154, the First Self-Amplifying mRNA Vaccine Approved for COVID in Adults. [Online] Available at: https://ir.arcturusrx.com/news-releases/news-release-details/japans-ministry-health-labour-and-welfare-approves-csl-and
4. Arcturus, 2025. European Commission Approves CSL and Arcturus Therapeutics’ KOSTAIVE®, the First Self-amplifying mRNA COVID-19 Vaccine. [Online]
   Available at: https://ir.arcturusrx.com/news-releases/news-release-details/european-commission-approves-csl-and-arcturus-therapeutics
5. Giles ML, Tabora C, Baccarini C, Barrientos L, Vargas JC, Montellano ME, et al. Immunogenicity and safety of self-amplifying mRNA COVID-19 vaccine (ARCT-2303), with or without co-administration of seasonal inactivated influenza vaccine in adults: a phase 3, randomised, controlled, observer-blind, multicentre study. EClinicalMedicine [Internet]. 2025 Aug 21;87:103428. Available from: https://doi.org/10.1016/j.eclinm.2025.103428
6. PatSnap Synapse, 2023. Japan’s Department of Health sanctions CSL and Arcturus’s ARCT‑154, an initial mRNA booster for adult COVID‑19 authorization. [Online]. Available at: https://synapse.patsnap.com/blog/japans-department-of-health-sanctions-csl-and-arcturuss-arct-154-an-initial-mrna-booster