A Clinical Study of the HCMV-TB Vaccine Candidate VIR-1778 in Healthy Adults

NCT07818824 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: HVTN 606
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 2

Brief Summary

This Phase 1, randomized, double-blind, placebo-controlled study will evaluate the safety, tolerability, and immune responses of the investigational HCMV-TB vaccine candidate VIR-1778 in adults in overall good health without HIV who are cytomegalovirus (CMV) seropositive. Participants will receive two doses of either VIR-1778 or placebo administered 12 weeks apart. The study will assess the safety of VIR-1778, its ability to induce immune responses against Mycobacterium tuberculosis (TB) antigens, and the presence of vaccine-derived virus in blood, saliva, and urine. The study is based on the hypothesis that VIR-1778 will be safe and well tolerated and will induce CD4+ and CD8+ T-cell responses against TB antigens. Approximately 116 participants will be enrolled.

Conditions

Tuberculosis

Keywords

Healthy Participants; Healthy Individuals; Tuberculosis; Vaccine

Outcome Measures

Primary Outcomes (6)

• Incidence of solicited local reactogenicity

  Incidence and severity of solicited local reactogenicity following receipt of study vaccine.

  Through 14 days after each study vaccination

• Incidence of solicited systemic reactogenicity

  Incidence and severity of solicited systemic reactogenicity following receipt of study vaccine.

  Through 14 days after each study vaccination

• Incidence of adverse events (AEs)

  Incidence of adverse events following receipt of study product.

  Through 52 weeks after last receipt of study product

• Incidence of serious adverse events (SAEs)

  Incidence of serious adverse events.

  Through 52 weeks after last receipt of study product

• Incidence of medically attended adverse events (MAAEs)

  Incidence of medically attended adverse events.

  Through 52 weeks after last receipt of study product

• Incidence of adverse events leading to early participant withdrawal or permanent discontinuation

  Incidence of adverse events resulting in early participant withdrawal or permanent discontinuation of study product

  Through 52 weeks after last receipt of study product

Secondary Outcomes (9)

• Frequency of insert-specific CD4 T-cell responses

  Up to 8 weeks after the first vaccination and up to 52 weeks after the second vaccination

• Functional parameters of insert-specific CD4 T-cell responses to synthetic TB peptides

  Up to 8 weeks after the first vaccination and up to 52 weeks after the second vaccination

• Phenotypic profile (markers of memory phenotype) of insert-specific CD4 T-cell responses

  Up to 8 weeks after the first vaccination and up to 52 weeks after the second vaccination

• Frequency of insert-specific CD8 T-cell responses

  Up to 8 weeks after the first vaccination and up to 52 weeks after the second vaccination

• Functional parameters of insert-specific CD8 T-cell responses to synthetic TB peptides

  Up to 8 weeks after the first vaccination and up to 52 weeks after the second vaccination

Study Arms (3)

VIR-1778 Low Dose

EXPERIMENTAL

Participants receive VIR-1778 at a dose of 5 × 10\^5 focus-forming units (ffu) administered as a 1 mL subcutaneous injection in the deltoid at Week 0 and Week 12.

Biological: VIR-1778 (5 × 10^5 ffu)

VIR-1778 High Dose

EXPERIMENTAL

Participants receive VIR-1778 at a dose of 5 × 10\^6 focus-forming units (ffu) administered as a 1 mL subcutaneous injection in the deltoid at Week 0 and Week 12.

Biological: VIR-1778 (5 × 10^6 ffu)

HT Diluent Placebo

PLACEBO COMPARATOR

Participants receive HT Diluent Placebo administered as a 1 mL subcutaneous injection in the deltoid at Week 0 and Week 12

Other: HT Diluent Placebo

Interventions

VIR-1778 (5 × 10^5 ffu) BIOLOGICAL

Live attenuated human cytomegalovirus (HCMV)-vectored tuberculosis (TB) vaccine candidate expressing seven Mycobacterium tuberculosis antigens (TB7Ag). Administered as a 1 mL subcutaneous injection in the deltoid at Week 0 and Week 12.

VIR-1778 Low Dose

VIR-1778 (5 × 10^6 ffu) BIOLOGICAL

Live attenuated human cytomegalovirus (HCMV)-vectored tuberculosis (TB) vaccine candidate expressing seven Mycobacterium tuberculosis antigens (TB7Ag). Administered as a 1 mL subcutaneous injection in the deltoid at Week 0 and Week 12.

VIR-1778 High Dose

HT Diluent Placebo OTHER

HT buffer placebo containing 20 mM histidine and 10% trehalose-dihydrate without active vaccine. Administered as a 1 mL subcutaneous injection in the deltoid at Week 0 and Week 12.

HT Diluent Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General and Demographic Criteria
• At least 18 years old at screening and up to 55 years old on day of enrollment.
• Access to a participating HVTN CRS and willingness to be followed for the planned duration of the study.
• Demonstrates an understanding of the study and is able and willing to provide informed consent.
• Agrees not to enroll in another study of an investigational agent during participation in the trial. If a potential participant is already enrolled in another clinical trial, approvals are required prior to enrollment into HVTN 606.
• In good general health according to the clinical judgment of the site investigator.
• Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgment of the site investigator.
• Willing to not donate blood, sperm, or other tissues until after the last required protocol clinic visit.
• CMV seropositive.
• Male volunteers with partners of pregnancy potential must agree to have their partners use contraception through the end of the study (does not include long-term follow-up).
• For Part A only: Women who are not of pregnancy potential or male volunteers. Any individual may be enrolled if they are not of pregnancy potential.
• For Part B only: Women volunteers who are of pregnancy potential must
• Be willing to use an approved method of highly effective contraception from 14 days before enrollment through the end of the study
• Refrain from egg donation and in vitro fertilization from the time of study product administration through the end of the study
• Have negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test at screening (ie, prior to randomization) and prior to study product administration on the day of study product administration. Women who are NOT of pregnancy potential due to having undergone hysterectomy or salpingectomy or tubal ligation or bilateral oophorectomy (verified by medical records) are not required to undergo pregnancy testing.

You may not qualify if:

• Known significant exposure to TB in the 2 years prior to enrollment, as determined by the site investigator based on potential participant report and available medical records.
• Note: Significant exposure is defined as close contact with a person who has active TB and has not completed TB treatment. Close contact is defined as sleeping in the same contiguous house/dwelling, and/or working or socializing in close proximity in an enclosed space frequently (eg, several times a week).
• History of prior active TB disease, as determined by the site investigator based on participant report and available medical, laboratory, or radiographic records.
• Current anti-TB prophylaxis or therapy.
• Evidence of active TB disease as determined by the site investigator.
• Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires approval.
• Pregnant or breastfeeding.
• Receipt of investigational research agents with a half-life of 7 or fewer days within 4 weeks prior to enrollment. If a potential participant has received investigational agents with a half-life of more than 7 days (or unknown half-life) within the past year, approval is required for enrollment.
• Investigational TB vaccine(s) or CMV-based vaccine received in prior vaccine trials or BCG vaccination outside infancy. For volunteers who have received control/placebo in a TB vaccine trial, eligibility will be determined on a case-by-case basis.
• Investigational non-TB vaccine(s) or non-CMV vaccine received within the last 1 year in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA or by the national regulatory authority where the volunteer is enrolling. For volunteers who have received control/placebo in an experimental vaccine trial, eligibility will be determined on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 1 year ago, eligibility for enrollment will be determined on a case-by-case basis.
• Receipt of any of the following within 4 weeks prior to enrollment:
• Live replicating vaccine
• Any mRNA-based vaccine with FDA licensure, FDA EUA, or WHO EUL
• ACAM2000 vaccine \> 28 days prior with a vaccination scab still present
• Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator, such as glucocorticoid use, ≥ prednisone 10 mg/day within 3 months prior to enrollment.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

ACSA CRS Site# 30259

Iquitos, Peru

Location

Via Libre CRS Site# 31909

Lima, 15001, Peru

Location

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: September 14, 2026
• Study Start (Estimated): November 6, 2026
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: September 14, 2026

Record last verified: 2026-08

Locations

PE (2)