A Study Exploring the Effect of Adjuvanted RZV or RSVPreF3 Vaccines on Coronary Plaque Progression in Adults >=50 Years of Age at Risk for Cardiovascular Events

A Randomized, Observer-blind, Placebo-controlled Exploratory Study to Evaluate Whether Administration of Adjuvanted RZV or RSVPreF3 Vaccine Can Attenuate Coronary Plaque Progression in Individuals 50 Years of Age and Above Who Are at Risk for Cardiovascular Events

This study is designed to evaluate whether the adjuvanted recombinant zoster vaccine (RZV) or the adjuvanted respiratory syncytial virus PreFusion protein 3 (RSVPreF3) vaccine can attenuate the progression of coronary plaque in adult individuals at risk for cardiovascular events.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Combination product: Placebo; Combination product: Adjuvanted RZV vaccine; Biological: Adjuvanted RSVPreF3 vaccine

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants, including participants with a caregiver who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written or witnessed informed consent obtained from the participant prior to performance of any study-specific procedure.
• Medically stable patients as established by medical history and clinical examination at screening.
• Male or female participants >=50 years of age (YOA) at the time of the first study intervention administration.
• Participants with documented history of coronary artery calcium (CAC) and two or more risk factors for cardiovascular disease.
• Participants with estimate glomerular filtration rate (eGFR) >=45 mL/min/1.73m^2.
• Participants who can undergo serial CCTA.
• Participants with no planned changes in medical therapies through the course of the study.
• Participants of non-childbearing potential may be enrolled in the clinical study.

• Participant of childbearing potential may be enrolled in the study if the participant:

  • has practiced adequate contraception for at least 30 days prior to study intervention administration, and
  • has a negative pregnancy test within 24 hours prior to the study intervention administration and prior to each CCTA, and
  • has agreed to continue adequate contraception during the entire duration of the study and for 8 weeks after completion of the study.

Exclusion Criteria:

Cardiovascular conditions

• Prior atherosclerotic cardiovascular disease (ASCVD) event.
• History or planned coronary artery bypass grafting (CABG), any cardiovascular surgery, percutaneous coronary intervention (PCI), or valvular intervention.
• Heart failure with Class III or IV symptoms according to the New York Heart Association and/or unstable heart failure at the screening visit.

Other medical conditions

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Acute or unstable chronic conditions, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination and/or laboratory screening tests.
• Recurrent history or uncontrolled neurological disorders or any neuroinflammatory, congenital neurological conditions, encephalopathies, or seizures.
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the clinical study.
• Condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study.
• History of malignancy <=5 years, radiation therapy or systemic therapy prior to signing informed consent.
• Any history of dementia or any medical condition that moderately or severely impairs cognition.

Prior/Concomitant therapy

• Previous vaccination against Herpes Zoster (HZ) (investigational or licensed vaccine) and/or planned administration of vaccination against HZ during the study period other than the vaccine administered during the study.
• Previous vaccination with an RSV vaccine (investigational or licensed vaccine) and/or planned administration of an RSV vaccine during the study period other than the adjuvanted RSVPreF3 vaccine administered during the study.
• Use of any investigational or non-registered product other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -29 to Day 1), or their planned use during the study period.
• Administration of immunoglobulins or other blood products or plasma derivatives during the period starting 90 days before the study intervention or planned administration during the study period.
• Chronic administration of immune-modifying drugs and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study.
• Planned administration/administration of a vaccine in the period starting 30 days before the first dose/each dose and ending 30 days after the last dose/each dose of study intervention(s) administration, with the exception of SARS-CoV-2 and inactivated seasonal influenza (flu) vaccine which can be administered up to 14 days before or 14 days after study intervention administration.

Prior/Concurrent clinical study participation

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention drug/invasive medical device.
• Contraindications to CCTA.

Other exclusion criteria

• Bedridden participants.
• Pregnant or lactating participant.
• History of current chronic alcohol consumption and/or drug abuse, based on investigator's judgment.
• Any study personnel or their immediate dependents, family, or household members.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Participants in this group receive placebo, the first dose being administered at Day 1 and the second dose at Month 2.	Combination product: Placebo; Placebo will be administered intramuscularly.
Experimental: Adjuvanted RZV group; Participants in this group receive the adjuvanted RZV vaccine, the first dose being administered at Day 1 and the second dose at Month 2.	Combination product: Adjuvanted RZV vaccine; Adjuvanted RZV vaccine will be administered intramuscularly.
Experimental: Adjuvanted RSVPreF3 group; Participants in this group receive a single dose of placebo at Day 1 and a single dose of the adjuvanted RSVPreF3 vaccine at Month 2.	Combination product: Placebo; Placebo will be administered intramuscularly.; Biological: Adjuvanted RSVPreF3 vaccine; Adjuvanted RSVPreF3 vaccine will be administered intramuscularly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in total coronary non-calcified plaque volume (NCPV) as measured on coronary computed tomography angiography (CCTA)	At Baseline (Day 1) and at Month 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in total coronary plaque volume as measured on CCTA		At Baseline (Day 1) and at Month 14
Change from Baseline in low attenuation plaque as measured on CCTA		At Baseline (Day 1) and at Month 14
Change from Baseline in peri-coronary fat attenuation index as measured on CCTA		At Baseline (Day 1) and at Month 14
Number of participants with any serious adverse events (SAEs)	An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, is an abnormal pregnancy outcome or is a suspected transmission of any infectious agent via an authorized medicinal product. Any = occurrence of the SAE regardless of intensity grade or relation to the study vaccination.	From Day 1 to Month 15
Number of participants with SAEs related to study participation or study procedures		From start of screening (Day -15) to Month 15
Number of participants with SAEs leading to withdrawal from the study		From Day 1 to Month 15

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): May 4, 2029
• Study Completion (Estimated): May 4, 2029

Study Registration Dates

• First Submitted: July 14, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 17, 2026

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Respiratory syncytial virus; RSV; Herpes Zoster; Coronary plaque; Adjuvanted Recombinant zoster vaccine; Adjuvanted RSVPreF3 vaccine
• Additional Relevant MeSH Terms: Varicella Zoster Virus Infection; Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Cardiovascular Diseases; Herpes Zoster
• Other Study ID Numbers: 309767

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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