Chronic Hepatitis B
Conditions
Brief summary
The goal of this clinical study is to learn more about GS-2829 and GS-6779 in healthy participants and participants with CHB.
Interventions
BIOLOGICALGS-2829
Administered intramuscularly
BIOLOGICALGS-6779
Administered intramuscularly
BIOLOGICALPlacebo
Administered intramuscularly
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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]) | 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. |
| Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | 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]) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥ 3-Fold Increase in Vaccine-Induced Hepatitis B Virus (HBV) Specific T-Cell Responses | 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]) | 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). |
| Mean Peak Levels of Vaccine-Induced HBV Specific T-Cell Responses | 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]) | 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. |
Countries
New Zealand, Taiwan
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Participant flow
Recruitment details
Participants were enrolled at study sites in New Zealand and Taiwan.
Pre-assignment details
148 participants (114 in Phase 1a and 34 in Phase 1b) were screened.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 81 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 48 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Race Other or More Than One Race | 0 Participants |
| Race/Ethnicity, Customized Race White | 21 Participants |
| Region of Enrollment New Zealand | 57 Participants |
| Region of Enrollment Taiwan | 0 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 10 | 0 / 8 | 0 / 9 | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 6 |
| other Total, other adverse events | 8 / 8 | 8 / 8 | 8 / 8 | 8 / 8 | 9 / 9 | 9 / 10 | 6 / 8 | 5 / 8 | 6 / 8 | 3 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 1 / 9 | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 6 |
Outcome results
None listed