Study of HBV Therapeutic Vaccines GS-2829 and GS-6779 in Healthy Participants and Participants With Chronic Hepatitis B

A Phase 1a/1b Study to Evaluate the Safety and Tolerability of Repeated Doses of Nonreplicating Arenavirus Vector Therapeutic Vaccines GS-2829 and GS-6779 in Healthy Participants and Participants With Chronic Hepatitis B (CHB)

The goal of this clinical study is to learn more about GS-2829 and GS-6779 in healthy participants and participants with CHB.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Biological: GS-2829; Biological: GS-6779; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research (NZCR)
• Taiwan
  • Chiayi City, Taiwan, 60002
    • Chia-Yi Christian Hospital
  • Chiayi City, Taiwan, 600
    • St. Martin De Porres Hospital
  • Kaohsiung City, Taiwan, 82445
    • E-DA Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Hospital
  • Kaohsiung City, Taiwan, 833
    • Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital
  • Tainan, Taiwan, 7428
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100229
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 33305
    • Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

Phase 1a and 1b:

• Body mass index (BMI) of ≤ 32.0 kg/m^2.
• Non-diabetic without impaired glucose tolerance.
• No evidence of cardiac disease based on 12 lead electrocardiogram (ECG).

Phase 1a (Healthy Individuals) only:

• Aged 18 through 60 years.
• No prior history of Hepatitis B infection with a negative hepatitis B surface antigen (HBsAg) and Hepatitis B (HBV) core antibody.

Phase 1b (Virally Suppressed chronic hepatitis B (CHB) Individuals)):

• Aged 18 through 65 years.
• Documented CHB and HBsAg ≤ 5000 IU/mL at screening.
• No evidence of advanced fibrosis by Fibroscan (defined as Fibroscan < 9 kilo pascal (kPa) within 6 months of screening).
• Diagnosed with CHB on suppressive oral antiviral for ≥ 6 months.
• Must have received an approved HBV-active oral antiviral agent for ≥ 6 months prior to screening with HBV DNA below lower limit of quantification (LLOQ) for ≥ 3 months prior to screening and with no plan to stop HBV-active antivirals during the study.

Key Exclusion Criteria:

Phase 1a and 1b:

• Use of any systemic antibiotics within 30 days of screening.
• Receipt of any HBV vaccine within 12 months of screening visit or planning HBV vaccination during the study period.
• Receipt of any investigational product within 3 months or vaccine within 3 months of screening (with the exception of influenza and severe acute respiratory syndrome (SARs) coronavirus (COV) - 2 (SARS-CoV-2) vaccines, which if needed, should be administered at least 14 days before or after an investigational product administration).
• Receipt of immunoglobulin or other blood products within 3 months of screening.
• Positive serum pregnancy test at screening or positive urine pregnancy on Day 1.
• Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or is expected to receive these agents during the study (eg, corticosteroids, immunoglobulins, other immune or cytokine-based therapies).
• Participation in any other clinical study (including observational studies) without prior approval from the sponsor is prohibited while participating in the study.

Note - Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a : Cohort 1 (Healthy Participants) : GS-2829 Low Dose (2 injections); Healthy participants will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 focus-forming unit (FFU)/mL) or placebo as intramuscular (IM) injection on Days 1 and 57.	Biological: GS-2829; Administered intramuscularly; Biological: Placebo; Administered intramuscularly
Experimental: Phase 1a : Cohort 2 (Healthy Participants) : GS-6779 Low Dose (2 injections); Healthy participants will receive a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57.	Biological: GS-6779; Administered intramuscularly; Biological: Placebo; Administered intramuscularly
Experimental: Phase 1a : Cohort 3 (Healthy Participants) : GS-2829 and GS-6779 Low Dose (2 cycles); Healthy participants will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection, on Days 29 and 85.	Biological: GS-2829; Administered intramuscularly; Biological: GS-6779; Administered intramuscularly; Biological: Placebo; Administered intramuscularly
Experimental: Phase 1a : Cohort 4 (Healthy Participants) : GS-2829 and GS-6779 High Dose (2 cycles); Healthy participants will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection, on Days 1 and 57; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection, on Days 29 and 85.	Biological: GS-2829; Administered intramuscularly; Biological: GS-6779; Administered intramuscularly; Biological: Placebo; Administered intramuscularly
Experimental: Phase 1a : Cohort 8 (Healthy Participants) : GS-2829 and GS-6779 High Dose (3 cycles); Healthy participants will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1, 57 and 113; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29, 85 and 141.	Biological: GS-2829; Administered intramuscularly; Biological: GS-6779; Administered intramuscularly; Biological: Placebo; Administered intramuscularly
Experimental: Phase 1b : Cohort 5 (VS Participants with CHB) : GS-2829 and GS-6779 Low Dose (2 cycles); Virally suppressed (VS) participants with Chronic Hepatitis B (CHB) will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 29 and 85.	Biological: GS-2829; Administered intramuscularly; Biological: GS-6779; Administered intramuscularly; Biological: Placebo; Administered intramuscularly
Experimental: Phase 1b : Cohort 6 (VS Participants with CHB) : GS-2829 and GS-6779 High Dose (2 cycles); VS participants with CHB will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29 and 85.	Biological: GS-2829; Administered intramuscularly; Biological: GS-6779; Administered intramuscularly; Biological: Placebo; Administered intramuscularly
Experimental: Phase 1b : Cohort 7 (VS Participants with CHB) : GS-2829 and GS-6779 High Dose (3 cycles); VS participants with CHB will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1, 57 and 113; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29, 85 and 141.	Biological: GS-2829; Administered intramuscularly; Biological: GS-6779; Administered intramuscularly; Biological: Placebo; Administered intramuscularly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Treatment-emergent adverse events (TEAEs) were defined as any AE with a start date on or after the study drug start date; or any AE that led to premature discontinuation of study drug. An SAE is defined as an event that, at any dose, results in the following: Death, a life-threatening situation, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.	First dose date to end of study (followed up to 24 weeks post last dose (up to Day 225 [cohorts 1, 2], Day 253 [cohorts 3, 4, 5, 6], and Day 309 [cohorts 7 and 8])
Percentage of Participants With Treatment-Emergent Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any time postbaseline. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed postbaseline will be considered treatment emergent.	First dose date to end of study (followed up to 24 weeks post last dose (up to Day 225 [cohorts 1, 2], Day 253 [cohorts 3, 4, 5, 6], and Day 309 [cohorts 7 and 8])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With ≥ 3-Fold Increase in Vaccine-Induced Hepatitis B Virus (HBV) Specific T-Cell Responses	Vaccine-induced HBV-specific T cell responses were measured using an interferon-gamma (IFN-γ), enzyme-linked immunospot (ELISpot) assay with a readout of spot forming cells (SFCs) /10^6 peripheral blood mononuclear cells (PBMCs). Total response was the sum of the dimethylsulfoxide (DMSO) -adjusted averages for the 4 HBV peptides (HBV core + HBV polymerase (pol) A + HBV pol B + HBV surface antigen (sAg)). Response was defined as a ≥ 3-fold increase over baseline in vaccine-induced HBV-specific total T cell response (measured using the IFN-γ ELISpot assay). A participant's highest fold-increase postbaseline was utilized for analysis of responder/non-responder. Participants with missing values for fold change over baseline were counted as failures (missing = failure).	Up to 24 weeks post last dose (up to Day 225 [cohorts 1, 2]) or up to 12 weeks post last dose (up to Day 169 [cohorts 3, 4, 5, 6]; Day 225 [cohorts 7 and 8])
Mean Peak Levels of Vaccine-Induced HBV Specific T-Cell Responses	Vaccine-induced HBV-specific T cell responses were measured using an IFN-γ ELISpot assay with a readout of SFCs/10^6 PBMCs. Total response was the sum of the DMSO-adjusted averages for the 4 HBV peptides (HBV Core + HBV Pol A + HBV Pol B + HBV sAg). Peak values were the highest posttreatment value for an individual participant and then means were calculated across the participants in a cohort.	Up to 24 weeks post last dose (up to Day 225 [cohorts 1, 2]) or up to 12 weeks post last dose (up to Day 169 [cohorts 3, 4, 5, 6]; Day 225 [cohorts 7 and 8])

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Gane E J et al. Safety, tolerability and immunogenicity of GS-2829 and GS-6779, a novel arenaviral vectored therapeutic hepatitis B vaccine: results from a phase 1a study in healthy participants. Poster THU-246. Presented at European Association for the Study of the Liver (EASL), 07-10 May 2025, Amsterdam, The Netherlands. J Hepatol 2025;82(S1):S831.
• Gane E J, et al. Safety, tolerability, immunogenicity, and antiviral efficacy of GS-2829 and GS-6779, a novel, arenaviral-vectored, therapeutic hepatitis B vaccine: Results from a phase 1b study in virally suppressed patients with chronic hepatitis B. *Hepatology*. 2025;72(Suppl 1):197. Presented at: AASLD The Liver Meeting; November 7-11, 2025; San Diego, CA.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2023
• Primary Completion (Actual): January 15, 2025
• Study Completion (Actual): January 15, 2025

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 16, 2023

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Hepatitis B; Hepatitis B, Chronic
• Other Study ID Numbers: GS-US-642-5670

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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