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

NCT05012943 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ARCT-154-01
• Study Type: interventional
• Target: 19,474
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

COVID-19 Vaccines

Keywords

ARCT-154; COVID-19; SARS-CoV-2; Immunogenicity; Efficacy

Outcome Measures

Primary Outcomes (6)

• Number of Participants Reporting Solicited Local Adverse Reactions (ARs)

  Solicited local ARs included injection site erythema, injection site pain, injection site induration/swelling, and injection site tenderness. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  Within 7 days after Dose 1 and Dose 2 (up to Day 7 and 36)

• Number of Participants Reporting Solicited Systemic ARs

  Solicited systemic ARs included arthralgia, chills, diarrhea, dizziness, fatigue, fever (categorized by measured body temperature), headache, myalgia, and nausea/vomiting. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  Within 7 days after Dose 1 and Dose 2 (up to Day 7 and 36)

• Number of Participants Reporting Unsolicited Adverse Events (AEs)

  Unsolicited AEs were defined as any spontaneously reported or discovered AE. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  Approximately 28 days after Dose 1 and Dose 2 (Day 1 to Day 29 and Day 29 to Day 57)

• Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation

  An MAAE was defined as an AE that led to an unscheduled visit (including a telemedicine visit) with a healthcare provider (\[HCP\], e.g., nurse, nurse practitioner, physician's assistant, physician). An SAE was defined as any event that resulted in death, was immediately life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect arising from a pregnancy conceived after receipt of study vaccine. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  Day 1 to Day 92

• Number of Participants With Neutralizing Antibody (NAb) Responses

  Data are presented for the number of participants with a NAb seroconversion response as determined by the surrogate virus neutralization test (sVNT). Seroconversion was defined as a ≥4-fold increase in antibody concentration from baseline.

  Day 57

• Number of Participants With a First Occurrence of Coronavirus Disease 2019 (COVID-19)

  COVID-19 was defined as a positive SARS-CoV-2 test and at least one of the following that was a new or worsening finding: ⦁ Fever or chills ⦁ Cough ⦁ Shortness of breath or difficulty breathing ⦁ Fatigue ⦁ Muscle or body aches ⦁ Headache ⦁ New loss of taste or smell ⦁ Sore throat ⦁ Congestion or runny nose ⦁ Nausea or vomiting ⦁ Diarrhea Data are presented for the number of participants with a first occurrence of COVID-19 with no evidence of prior infection.

  Day 36 to Day 92

Secondary Outcomes (11)

• Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies

  Days 1, 29, 57 and 92

• Geometric Mean Fold Rise in SARS-CoV-2 Neutralizing Antibody Titers

  Days 29, 57, 92

• Number of Participants Seroconverting for Neutralizing Antibodies

  Days 29, 57 and 92

• Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies

  Days 1, 29, 57, 92

• Geometric Mean Fold Ratio of Spike Protein IgG Binding Antibodies

  Days 29, 57, 92

Study Arms (3)

ARCT-154

EXPERIMENTAL

Each participant is planned to receive a two-dose vaccination series of ARCT-154 at a dose of 5 µg with 28 day interval in the first vaccination series.

Biological: ARCT-154 Self-Amplifying RNA SARS-CoV-2 Vaccine

Placebo

PLACEBO COMPARATOR

Each participant is planned to receive a two-dose vaccination series of placebo (normal saline) with 28 day interval in the first vaccination series.

Other: Placebo (normal saline)

Astra Zeneca COVID-19 vaccine

ACTIVE COMPARATOR

Each participant is planned to receive a two-dose vaccination series of Astra Zeneca COVID-19 vaccine with 28 day interval in the first vaccination series.

Biological: Astra Zeneca COVID-19 vaccine

Interventions

ARCT-154 Self-Amplifying RNA SARS-CoV-2 Vaccine BIOLOGICAL

ARCT-154 Self-Amplifying RNA SARS-CoV-2 Vaccine

ARCT-154

Placebo (normal saline) OTHER

Normal saline with the same volume as of ARCT-154

Placebo

Astra Zeneca COVID-19 vaccine BIOLOGICAL

Astra Zeneca COVID-19 vaccine (ChAdOx1 nCoV-19)

Astra Zeneca COVID-19 vaccine

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals who:
• are able to provide consent
• agree to comply with all study visits and procedures
• are of childbearing potential and sexually active must be willing to adhere to contraceptive requirements
• are male or female ≥18 years of age (or, for Phase 1, 18 to \< 60 years of age)
• are at higher risk of developing COVID-19 based on where they work or live

You may not qualify if:

• Individuals who:
• Significant infection or other acute illness, including body temperature \>100.4°F (\>38.0°C) on the day prior to or Day 1. Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator.
• Pregnant or breastfeeding.
• Close contact with a person known to be SARS-CoV-2 positive or with a clinical diagnosis of COVID-19 within 7 days prior to enrollment. Participants meeting this criterion who remain asymptomatic for 7 days may be rescheduled for enrollment within the relevant windows.
• Known history of anaphylaxis, urticaria, or other significant adverse reaction to the vaccine or its excipients.
• Known history of anaphylaxis to other vaccines.
• Bleeding disorder considered a contraindication to intramuscular (IM) injection or phlebotomy.
• Immunosuppressive or immunodeficient state, asplenia, recurrent severe infections, or known to be HIV positive.
• An underlying clinically significant acute or chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Prior/Concomitant Therapy
• Has previously received investigational or approved MERS-CoV, SARS-CoV, SARS-CoV-2 vaccines or who have plans to receive off-study COVID-19 vaccines.
• Has received a live replicating vaccine within 28 days prior to each study vaccination or a licensed inactivated or non-replicating vaccine within 14 days prior to first study vaccination.
• Has received treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, within 6 months prior to Screening, or planned receipt throughout the study. If systemic corticosteroids have been administered short term (\<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days prior to first study vaccine administration. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
• Has received systemic immunoglobulins or blood products within 3 months prior to first study vaccine administration or plans to receive such products during the study.
• Demonstrated inability to comply with the study procedures.

Sponsors & Collaborators

• Vinbiocare Biotechnology Joint Stock Company: lead
• Arcturus Therapeutics, Inc.: collaborator

Study Sites (3)

Hanoi Medical University

Hanoi, Hanoi, 00000, Vietnam

Location

Military Medical University

Hanoi, Hanoi, 00000, Vietnam

Location

Pasteur Institute

Ho Chi Minh City, Ho Chi Minh, 00000, Vietnam

Location

MeSH Terms

Conditions

COVID-19

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Nguyen Xuan Hung
• Organization: Vinmec Healthcare System

v.hungnx1@vinmec.com

+84-865438388

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Observer-blind design: Investigators, site staff, participants, CRO staff, Sponsor representatives with oversight of study conduct or study-related assessments will remain blinded to vaccine assignments for the study duration.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1, 2, 3a, 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 at around 2 months after the first series on Day 92 and 120. Each participant is planned to receive a two-dose vaccination series of ARCT-154 at a dose of 5 µg or a two-dose vaccination series of placebo (saline) in the first series. Participants in Phase 2, 3a who received 2 doses of ARCT-154 vaccine in the first vaccine series 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. Phase 3c: Participants will be randomly assigned to a study group to receive two-dose vaccination series of ARCT-154 at a dose of 5 µg or approved COVID-19 vaccine comparator (Astra Zeneca's COVID-19 vaccine).

Study Record Dates

• First Submitted: August 13, 2021
• First Posted: August 19, 2021
• Study Start: August 15, 2021
• Primary Completion: January 18, 2023
• Study Completion: January 18, 2023
• Last Updated: November 6, 2025
• Results First Posted: November 6, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

VN (3)