A Clinical Study to Evaluate the Safety and Immunogenicity of a Higher Dose of the Study Vaccine, VIR-1388, in HCMV-seropositive Adult Participants Without HIV

NCT07801456 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HVTN 146
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This study is to test an experimental HIV Vaccine. About 12 participants, aged 18-55 years and who already have cytomegalovirus (CMV) will take part in this study. Participants will come to the clinic for scheduled visits about 21 times over 12 months.

Conditions

Cytomegalovirus (CMV); HIV (Human Immunodeficiency Virus)

Keywords

Vaccine; HIV Vaccine; Healthy Participants

Outcome Measures

Primary Outcomes (14)

• Number of Participants with Local Reactions

  Local reactogenicity signs and symptoms will be collected for a minimum of 14 days following receipt of any study product

  Day of vaccination through 14 days after each vaccination

• Number of Participants with Systemic Reactions

  Systemic reactogenicity signs and symptoms will be collected for a minimum of 14 days following receipt of any study product

  Day of vaccination through 14 days after each vaccination

• Number of Participants with Serious Adverse Events (SAEs)

  Throughout the study, through 40 weeks after the last study product administration

• Number of Participants with Medically Attended Adverse Events (MAAEs)

  Throughout the study and for 40 weeks after the last study product administration

• Number of Participants with Adverse Events of Special Interest (AESIs)

  Throughout the study and for 40 weeks after the last study product administration

• Number of Participants with Adverse Events Leading to Early Study Withdrawal

  Throughout the study and for 40 weeks after the last study product administration

• Number of Participants with Adverse Events Leading to Permanent Discontinuation of Study Product

  Throughout the study and for 40 weeks after the last study product administration

• Number of Participants with Adverse Events

  Day of vaccination through 30 days after each vaccination

• Magnitude of HIV-1 Mfuse1-Specific CD4 T-Cell Responses

  Level of CD4 T-cell responses to HIV-1 Mfuse1, which contains parts of Gag, Pol, and Nef. Responses will be measured using intracellular cytokine staining (ICS) and flow cytometry.

  Baseline and 4 and 8 weeks after each vaccination

• Magnitude of HIV-1 Mfuse1-Specific CD8 T-Cell Responses

  Level of CD8 T-cell responses to HIV-1 Mfuse1, which contains parts of Gag, Pol, and Nef. Responses will be measured using intracellular cytokine staining (ICS) and flow cytometry.

  Baseline and 4 and 8 weeks after each vaccination

• Function of HIV-1 Mfuse1-Specific CD4 T-Cell Responses

  Function of CD4 T-cell responses to HIV-1 Mfuse1, as measured using intracellular cytokine staining (ICS) and flow cytometry

  Baseline and 4 and 8 weeks after each vaccination

• Function of HIV-1 Mfuse1-Specific CD8 T-Cell Responses

  Function of CD8 T-cell responses to HIV-1 Mfuse1, as measured using intracellular cytokine staining (ICS) and flow cytometry

  Baseline and 4 and 8 weeks after each vaccination

• Phenotypic Profile of HIV-1 Mfuse1-Specific CD4 T-Cell Responses

  Characteristics of CD4 T cells that respond to HIV-1 Mfuse1, as measured using flow cytometry

  Baseline and 4 and 8 weeks after each vaccination

• Phenotypic Profile of HIV-1 Mfuse1-Specific CD8 T-Cell Responses

  Characteristics of CD8 T cells that respond to HIV-1 Mfuse1, as measured using flow cytometry

  Baseline and 4 and 8 weeks after each vaccination

Secondary Outcomes (9)

• Number of Participants With VIR-1388 Detected in Plasma

  Vaccination Day 1 through Study Day 365

• Number of Participants With VIR-1388 Detected in Saliva

  Vaccination Day 1 through Study Day 365

• Number of Participants With VIR-1388 Detected in Urine

  Vaccination Day 1 through Study Day 365

• Magnitude of HIV-1 Mfuse1-Specific CD4 T-Cell Responses at Additional Timepoints responses to VIR-1388derived HIV-1 Mfuse1 (containing portions of Gag, Pol and Nef)

  Additional timepoints during the study, including 2 weeks after each vaccination, and 12 weeks, 24 weeks, and 40 weeks after second vaccination

• Magnitude of HIV-1 Mfuse1-Specific CD8 T-Cell Responses at Additional Timepoints

  Additional timepoints during the study, including 2 weeks after each vaccination and 12 weeks, 24 weeks, and 40 weeks after second vaccination

Study Arms (2)

VIR-1388

EXPERIMENTAL

VIR-1388 will be administered subcutaneously at study week 0 (month 0) and week 12 (month 3).

Biological: VIR-1388

Placebo

PLACEBO COMPARATOR

Placebo will be administered subcutaneously at study week 0 (month 0) and week 12 (month 3).

Biological: Placebo

Interventions

VIR-1388 BIOLOGICAL

Treatment 1 (T1): VIR-1388, 6.9 × 10\^7 ffu to be administered as three 1 mL subcutaneous (SC) injections (total dose = 3 mL) at week 0 (month 0) and week 12 (month 3).

VIR-1388

Placebo BIOLOGICAL

Control 1 (C1): Placebo for VIR-1388 \[HT Diluent Placebo\] to be administered as three 1 mL SC injections (total dose = 3 mL) at week 0 (month 0) and week 12 (month 3).

Placebo

Eligibility Criteria

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

You may qualify if:

• At least 18 years old at screening and up to 55 years old on day of enrollment.
• Access to a participating clinical research site 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.
• 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.
• Women who are not of pregnancy potential or male volunteers. Any individual may be enrolled if they are not of pregnancy potential
• Willingness to receive HIV test results.
• Hemogram/complete blood count (CBC)
• Hemoglobin:
• ≥ 11.0 g/dL for women
• ≥ 13.0 g/dL for men

You may not qualify if:

• Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires approval.
• Of pregnancy potential, 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 HIV vaccine(s) or CMV-based vaccine received in prior vaccine trials. For volunteers who have received control/placebo in a TB vaccine trial, eligibility will be determined on a case-by-case basis.
• Investigational vaccine(s) received within the last 1 year in a prior vaccine trial. Exceptions may be considered 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 Emergency Use Authorization (EUA), or WHO Emergency Use Listing (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.
• Required either oral or parenteral corticosteroids for an exacerbation 2 or more times within the past year; OR
• Needed emergency care, urgent care, hospitalization, or intubation for an acute asthma exacerbation within the past year (eg, would NOT exclude individuals with asthma who meet all other criteria but sought urgent/emergent care solely for asthma medication refills or coexisting conditions unrelated to asthma); OR
• Uses a short-acting rescue inhaler more than 2 days/week for acute asthma symptoms (ie, not for preventive treatment prior to athletic activity); OR uses medium-to-high-dose inhaled corticosteroids (greater than 250 mcg fluticasone or therapeutic equivalent per day), whether in single-therapy or dual-therapy inhalers (ie, with a long-acting beta agonist \[LABA\]); OR
• Asplenia or functional asplenia.
• Active duty and reserve US military personnel.

Sponsors & Collaborators

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

Study Sites (2)

Alabama CRS (Site # 31788)

Birmingham, Alabama, 35222, United States

Location

Beth Israel Deaconess Medical Center / BIDMC VCRS (Site #32077)

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

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

Study Record Dates

• First Submitted: August 31, 2026
• First Posted: September 3, 2026
• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): February 2, 2028
• Study Completion (Estimated): February 2, 2028
• Last Updated: September 3, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)