A Study of S-268019 for the Prevention of COVID-19

A Phase 3, Randomized, Observer-Blind, Placebo- Controlled Cross-over Study to Evaluate the Efficacy, Safety, and Immunogenicity of S-268019 for the Prevention of COVID-19

The main purpose of this study is to assess the efficacy of S-268019-b for the prevention of COVID-19 in the initial vaccination period prior to crossover in participants without evidence of infection before vaccination as compared to placebo.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2
• Intervention / Treatment: Drug: S-268019-b; Drug: Placebo

Detailed Description

Eligible participants will be randomized to receive either S-268019-b or placebo first and then will be crossed over to receive the opposite intervention. The study will consist of two treatment periods, an initial vaccination period (Day 1 to Day 224), and a crossover vaccination period (Day 225 to Day 435).

• Study Type: Interventional
• Enrollment (Actual): 9902
• Phase: Phase 3

Contacts and Locations

Study Locations

• Vietnam
  • Dak Lak
    • Buon Ma Thuot, Dak Lak, Vietnam
      • Buon Ma Thuot City Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Agree not to participate in any other SARS-CoV-2 prevention trial during the study follow-up.
• Capable of using Diary without difficulties (if applicable, with assistance by caregiver).

Exclusion Criteria:

• Current or history of a laboratory-confirmed diagnosis of SARS-CoV-2 infection or COVID-19.
• Unstable current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disease that, in the opinion of the investigator or subinvestigator, would constitute a safety concern or confound data interpretation.
• Immunosuppression (immunodeficiency, acquired immunodeficiency syndrome [AIDS], use of systemic steroids, use of immunosuppressants within the past 6 months prior to the first dose of study intervention, treatment for malignant tumors, other immunosuppressive therapy).
• Previous vaccination against SARS-CoV-2.
• Any inactivated vaccine received within 14 days prior to the first dose of study intervention.
• Any live vaccine received within 28 days prior to the first dose of study intervention.
• Immunoglobulin preparations, blood products, or a blood transfusion within 3 months prior to the first dose of study intervention.

Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S-268019-b, Then Placebo; Participants will first receive a dose of S-268019-b via intramuscular (IM) injection on Day 1 and Day 29 during the initial vaccination period. After the initial vaccination period, participants will then receive a placebo IM injection (matching S-268019-b) on Day 225 and Day 253.	Drug: S-268019-b; Solution for IM injection; Drug: Placebo; Saline solution for IM injection
Experimental: Placebo, Then S-268019-b; Participants will first receive a dose of placebo IM injection (matching S-268019-b) on Day 1 and Day 29 during the initial vaccination period. After the initial vaccination period, participants will then receive S-268019-b IM injection on Day 225 and Day 253.	Drug: S-268019-b; Solution for IM injection; Drug: Placebo; Saline solution for IM injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With First Occurrence of SARS-CoV-2 Reverse Transcription Polymerase Chain Reaction (RT-PCR)-Positive Symptomatic COVID-19 With Onset at Least 14 Days Following Second Vaccination During the Initial Vaccination Period	Participants without evidence of infection before vaccination (that is, seronegative and PCR-negative at baseline) were determined to have symptomatic COVID-19 when at least 1 protocol-specified COVID-19-related symptom and a positive RT-PCR test result were confirmed by the medical monitor within at least 14 days following the second vaccination. RT-PCR testing was based upon nasopharyngeal swab sampling at protocol-specified timepoints.	From Day 43 (14 days after the second dose administration) to Day 224

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period With Onset at Least 14 Days Following Second Vaccination	For participants without evidence of infection before vaccination (that is, seronegative and PCR-negative at baseline) who were confirmed to have symptomatic COVID-19 within at least 14 days following the second vaccination, the investigator evaluated if the maximum intensity during the course of the disease met protocol-specified criteria for severe COVID-19.	From Day 43 (14 days after the second dose administration) to Day 224
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Symptomatic COVID-19 in the Initial Vaccination Period	Participants without evidence of infection before vaccination (that is, seronegative and PCR-negative at baseline) were determined to have symptomatic COVID-19 when at least 1 protocol-specified COVID-19-related symptom and a positive RT-PCR test result were confirmed by the medical monitor. RT-PCR testing was based upon nasopharyngeal swab sampling at protocol-specified timepoints.	Up to Day 224
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period	For participants without evidence of infection before vaccination (that is, seronegative and PCR-negative at baseline) who were confirmed to have symptomatic COVID-19, the investigator evaluated if the maximum intensity during the course of the disease met the protocol-specified criteria for severe COVID-19.	Up to Day 224
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Symptomatic COVID-19 in the Initial Vaccination Period Regardless of Serostatus or PCR Status at Baseline With Onset at Least 14 Days Following Second Vaccination	A participant was determined to have symptomatic COVID-19 when at least 1 protocol-specified COVID-19-related symptom and a positive RT-PCR test result were confirmed by the medical monitor within at least 14 days following the second vaccination. RT-PCR testing was based upon nasopharyngeal swab sampling at protocol-specified timepoints.	From Day 43 (14 days after the second dose administration) to Day 224
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period With Onset at Least 14 Days Following Second Vaccination Regardless of Serostatus or PCR Status at Baseline	For participants confirmed to have symptomatic COVID-19 within at least 14 days following the second vaccination, the investigator evaluated if the maximum intensity during the course of the disease met the protocol-specified criteria for severe COVID-19.	From Day 43 (14 days after the second dose administration) to Day 224
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Symptomatic COVID-19 in the Initial Vaccination Period Regardless of Serostatus or PCR Status at Baseline	A participant was determined to have symptomatic COVID-19 when the participant had at least 1 protocol-specified COVID-19-related symptom and a positive RT-PCR test result confirmed by the medical monitor. RT-PCR testing was based upon nasopharyngeal swab sampling at protocol-specified timepoints.	Up to Day 224
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period Regardless of Serostatus or PCR Status at Baseline	For participants confirmed to have symptomatic COVID-19, the investigator evaluated if the maximum intensity during the course of the disease met the protocol-specified criteria for severe COVID-19.	Up to Day 224
Number of Participants With First Occurrence of Asymptomatic SARS-CoV-2 Infection in the Initial Vaccination Period	For participants without evidence of infection before vaccination (that is, seronegative and PCR-negative at baseline), asymptomatic SARS-CoV-2 infection was defined as having a positive result of anti-SARS-CoV-2 N-protein antibody test beginning 14 days following the second vaccination and not meeting the protocol-specified criteria of symptomatic COVID-19. Antibodies to SARS-CoV-2 N-protein were used to determine both natural infection and the incidence of asymptomatic infection acquired during the initial vaccination period of the study.	From Day 43 (14 days after the second dose administration) to Day 224
Percentage of Participants Experiencing Solicited Systemic Adverse Events	An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs were defined as the AEs that occurred within the first 7 days after each vaccination and were classified as one of the following: fever, nausea/vomiting, diarrhea, headache, fatigue, and myalgia. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to Day 224
Percentage of Participants Experiencing Solicited Local Adverse Events	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited local AEs were defined as the AEs that occurred within the first 7 days after each vaccination and were classified as one of the following: pain, erythema/redness, induration, and swelling. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to Day 224
Geometric Mean Titer (GMT) of SARS-CoV-2 Neutralizing Antibody	Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody level against SARS-CoV-2 was measured by a live virus neutralization assay. The GMT was calculated by taking the back transformation of the arithmetic mean of log-transformed titers. The 95% confidence interval was calculated based on the Student's t distribution of the log-transformed values, then back transformed to the original scale.	Day 57
Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibody	Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody level against SARS-CoV-2 was measured by a live virus neutralization assay. The GMFR was calculated by taking the back transformation of the arithmetic mean of the change from baseline in log-transformed titers. The 95% confidence interval was calculated based on the Student's t distribution of the change from baseline in the log-transformed values, then back transformed to the original scale.	Day 57
Seroconversion Rate of SARS-CoV-2 Neutralizing Antibody	Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody level against SARS-CoV-2 was measured by a live virus neutralization assay. Seroconversion was defined as a 4-times or higher from baseline in SARS-CoV-2 neutralizing antibody titer, where titer values reported as below the lower limit of quantification (LLOQ) were replaced by 0.5*LLOQ. Seroconversion rate was defined as the percentage of participants that underwent seroconversion. The 95% confidence interval was calculated using the Clopper-Pearson method.	Day 57
GMT of Anti-SARS-CoV-2 S-protein Immunoglobulin G (IgG) Antibody	Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody level against SARS-CoV-2 (anti-spike protein IgG antibody) was measured by a chemiluminescence immunoassay. The GMT was calculated by taking the back transformation of the arithmetic mean of log- transformed titers. The 95% confidence interval was calculated based on the Student's t distribution of the log-transformed values, then back transformed to the original scale.	Day 57
GMFR of Anti-SARS-CoV-2 S-protein IgG Antibody	Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The anti-spike protein IgG antibody was measured by a chemiluminescence immunoassay. The GMFR was calculated by taking the back transformation of the arithmetic mean of the change from baseline in log-transformed titers. The 95% confidence interval was calculated based on the Student's t distribution of the change from baseline in the log-transformed values, then back transformed to the original scale.	Day 57
Seroconversion Rate of Anti-SARS-CoV-2 S-protein IgG Antibody	Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The anti-spike protein IgG antibody was measured by a chemiluminescence immunoassay. Seroconversion was defined as a 4-times or higher from baseline in anti-spike protein IgG antibody titer, where titer values reported as below the LLOQ are replaced by 0.5*LLOQ and titer values reported as above the upper limit of quantification (ULOQ) are imputed at the ULOQ value. Seroconversion rate was defined as the percentage of participants that underwent seroconversion. The 95% confidence interval was calculated using the Clopper-Pearson method.	Day 57

Collaborators and Investigators

• Sponsor: Shionogi

Publications and helpful links

General Publications

• Dinh Thiem V, Van Anh PT, Van Men C, Hung DT, Pollard AJ, Kamitani A, Tada Y, Fukuyama H, Iwasaki Y, Ariyasu M, Sonoyama T. A SARS-CoV-2 recombinant spike protein vaccine (S-268019-b) for COVID-19 prevention during the Omicron-dominant period: A phase 3, randomised, placebo-controlled clinical trial. Vaccine. 2024 Jun 20;42(17):3699-3709. doi: 10.1016/j.vaccine.2024.04.084. Epub 2024 May 10.

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2021
• Primary Completion (Actual): December 19, 2022
• Study Completion (Actual): July 19, 2023

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: January 24, 2022
• First Posted (Actual): January 28, 2022

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: S-268019-b COVID-19 vaccine
• Other Study ID Numbers: 2126U0232

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No