NCT05012943

The ARCT-154 Self-Amplifying RNA Vaccine Efficacy Study (ARCT-154-01)

A Randomized, Observer-Blind, Controlled Study to Assess the Safety, Immunogenicity and Efficacy of the SARS-CoV-2 Self- Amplifying RNA Vaccine ARCT-154 in Adults

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 19,474 (actual)
• Sponsor: Vinbiocare Biotechnology Joint Stock Company · Industry
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Accepted

Summary

This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind study designed to evaluate the safety, immunogenicity and efficacy of ARCT-154 in adult participants to be enrolled in Vietnam. This study consists of four parts: Part 1 (Phase 1) will evaluate the safety of the study vaccines in 100 healthy individuals. Part 2 (Phase 2) will evaluate the safety and immunogenicity of the study vaccines in 300 healthy individuals. Part 3 (Phase 3a) will evaluate the safety, immunogenicity, and efficacy of the study vaccines in 600 individuals with and without underlying medical conditions. Part 4 (Phase 3b) will evaluate the safety and efficacy of the study vaccines in 16,000 individuals with and without underlying medical conditions. Part 5 (Phase 3c) will evaluate the safety and non-inferiority in immunogenicity of ARCT-154 vaccine vs. Astra Zeneca COVID-19 vaccine (ChAdOx1 nCoV-19) in 2400 individuals with and without underlying medical conditions. In Phase 1, healthy individuals 18 to \< 60 years of age will be enrolled. In Phase 2, 3a, and 3b, individuals 18 years of age and older will be enrolled including individuals with underlying medical conditions that put them at higher risk of complications of COVID-19 disease. Phase 1, Phase 2, Phase 3a and Phase 3b participants will be randomly assigned to a study group that will receive up to 2 vaccination series. Each vaccination series comprises two vaccinations at 28-day intervals: an initial vaccination series with vaccinations on Day 1 and Day 29 and an additional vaccination series around 2 months after the first series (on Day 92 and 120). Participants of Phase 2, 3a who received 2 doses of ARCT-154 vaccine will be rerandomized to receive either dose 3 of ARCT-154 on Day 92 plus placebo on Day 120 or placebo on Day 92 plus placebo on Day 120. For Phase 1, Phase 3b and participants in Phase 2 and 3a that received placebo in the first vaccination series, the participants will be switched over to the opposite vaccine in the second series. There is no second vaccination series for Phase 3c as all participants receive active vaccine in the initial series.

Detailed description

Phase 1 will enroll 100 healthy participants that are randomly assigned 3:1 to receive ARCT-154 or placebo (75:25) for the initial series of vaccinations. In Phase 2, 300 participants will be randomly assigned 3:1 to receive ARCT-154 or placebo for the initial series of vaccinations. Participants that received ARCT-154 in the initial series will be rerandomized 3:1 to receive ARCT or placebo on Day 92 followed by placebo on Day 120. In Phase 3a, 600 participants will be randomly assigned 3:1 to receive ARCT-154 or placebo for the initial series of vaccinations. Participants that received ARCT-154 in the initial series will be rerandomized 3:1 to receive ARCT or placebo on Day 92 followed by placebo on Day 120. In Phase 3b, \~16,000 participants will be randomly assigned 1:1 to receive ARCT-154 or placebo for the initial series of vaccinations. In Phase 3c, \~2,400 participants will be randomly assigned 1:1 to receive ARCT-154 or Astra Zeneca COVID-19 vaccine. Blood samples will be collected and reserved for Immunogenicity evaluation for the first 1500 participants (3c-1) and assays for immunogenicity evaluation will be performed for the first 800 participants. Phase 1 participants must be \<60 years of age and healthy. Phase 2, 3a, and 3b and 3c participants will include elderly (≥60 years) and those with comorbidities. For Phase 2, 3a, 3b and 3c, prior to randomization, participants will be stratified by age (\< 60 or ≥ 60 years of age) and for participants \< 60 years of age by risk of severe COVID 19. Participants will be followed up for approximately 1 year after completion of the initial vaccination series. An independent Data and Safety Monitoring Board (DSMB) will perform ongoing review of blinded and unblinded data. An independent blinded adjudication committee will adjudicate all suspected COVID-19 cases to determine if they meet the primary endpoint requirements.

Conditions

• COVID-19 Vaccines

Interventions

Type	Name	Description
BIOLOGICAL	ARCT-154 Self-Amplifying RNA SARS-CoV-2 Vaccine	ARCT-154 Self-Amplifying RNA SARS-CoV-2 Vaccine
OTHER	Placebo (normal saline)	Normal saline with the same volume as of ARCT-154
BIOLOGICAL	Astra Zeneca COVID-19 vaccine	Astra Zeneca COVID-19 vaccine (ChAdOx1 nCoV-19)

Timeline

• Start date: 2021-08-15
• Primary completion: 2023-01-18
• Completion: 2023-01-18
• First posted: 2021-08-19
• Last updated: 2025-11-06
• Results posted: 2025-11-06

Locations

3 sites across 1 country: Vietnam

Regulatory

• FDA-regulated drug study