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

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

Official Title
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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)

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Biological: GS-2829
* Biological: GS-6779
* Biological: Placebo for GS-2829
* Biological: Placebo for GS-6779


Participation Criteria
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Eligibility Criteria
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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 ECG. Phase 1a (Healthy Individuals) only: Aged 18 through 60 years. No history of Hepatitis B infection with a negative Hepatitis B virus (HBV) core Antibody. Phase 1b (Virally suppressed 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 kPa within 6 months of screening). Diagnosed with chronic hepatitis B on suppressive oral antiviral for ≥ 6 months. 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 coronavirus 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: GS-2829 Dose A or Placebo<br>Healthy participants will receive GS-2829 Dose A or placebo for GS-2829. | Biological: GS-2829<br>* Administered intramuscularly<br>Biological: Placebo for GS-2829<br>* Administered intramuscularly<br>|
| Experimental: Cohort 2: GS-6779 Dose B or Placebo<br>Healthy participants will receive GS-6779 Dose B or placebo for GS-6779. | Biological: GS-6779<br>* Administered intramuscularly<br>Biological: Placebo for GS-6779<br>* Administered intramuscularly<br>|
| Experimental: Cohort 3: GS-2829 Dose A or Placebo + GS-6779 Dose B or Placebo<br>Healthy participants will receive GS-2829 Dose A or placebo for GS-2829 and GS-6779 Dose B or placebo for GS-6779. | Biological: GS-2829<br>* Administered intramuscularly<br>Biological: GS-6779<br>* Administered intramuscularly<br>Biological: Placebo for GS-2829<br>* Administered intramuscularly<br>Biological: Placebo for GS-6779<br>* Administered intramuscularly<br>|
| Experimental: Cohort 4: GS-2829 Dose C or Placebo + GS-6779 Dose D or Placebo<br>Healthy participants will receive GS-2829 Dose C or placebo for GS-2829 and GS-6779 Dose D or placebo for GS-6779. | Biological: GS-2829<br>* Administered intramuscularly<br>Biological: GS-6779<br>* Administered intramuscularly<br>Biological: Placebo for GS-2829<br>* Administered intramuscularly<br>Biological: Placebo for GS-6779<br>* Administered intramuscularly<br>|
| Experimental: Cohort 5: GS-2829 Dose A or Placebo + GS-6779 Dose B or Placebo<br>Participants with Chronic Hepatitis B (CHB) who are virally suppressed will receive GS-2829 Dose A or placebo for GS-2829 and GS-6779 Dose B or placebo for GS-6779. | Biological: GS-2829<br>* Administered intramuscularly<br>Biological: GS-6779<br>* Administered intramuscularly<br>Biological: Placebo for GS-2829<br>* Administered intramuscularly<br>Biological: Placebo for GS-6779<br>* Administered intramuscularly<br>|
| Experimental: Cohort 6: GS-2829 Dose C or Placebo + GS-6779 Dose D or Placebo<br>Participants with Chronic Hepatitis B (CHB) who are virally suppressed will receive GS-2829 Dose C or placebo for GS-2829 and GS-6779 Dose D or placebo for GS-6779. | Biological: GS-2829<br>* Administered intramuscularly<br>Biological: GS-6779<br>* Administered intramuscularly<br>Biological: Placebo for GS-2829<br>* Administered intramuscularly<br>Biological: Placebo for GS-6779<br>* Administered intramuscularly<br>|
| Experimental: Cohort 7: GS-2829 Dose C or Placebo + GS-6779 Dose D or Placebo<br>Participants with CHB who are virally suppressed will receive GS-2829 Dose C or placebo for GS-2829 and GS-6779 Dose D or placebo for GS-6779. | Biological: GS-2829<br>* Administered intramuscularly<br>Biological: GS-6779<br>* Administered intramuscularly<br>Biological: Placebo for GS-2829<br>* Administered intramuscularly<br>Biological: Placebo for GS-6779<br>* Administered intramuscularly<br>|
| Experimental: Cohort 8: GS-2829 Dose C or Placebo + GS-6779 Dose D or Placebo<br>Healthy participants will receive GS-2829 Dose C or placebo for GS-2829 and GS-6779 Dose D or placebo for GS-6779. | Biological: GS-2829<br>* Administered intramuscularly<br>Biological: GS-6779<br>* Administered intramuscularly<br>Biological: Placebo for GS-2829<br>* Administered intramuscularly<br>Biological: Placebo for GS-6779<br>* Administered intramuscularly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 for Cohorts 1 and 2; Up to Day 309 for Cohorts 3-8) | 
| 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 for Cohorts 1 and 2; Up to Day 309 for Cohorts 3-8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Vaccine-induced Immune Response |  | First dose date to end of study followed up to 24 weeks post last dose (Up to Day 225 for Cohorts 1 and 2; Up to Day 309 for Cohorts 3-8) | 
| Magnitude of Vaccine-Induced Immune Responses as Measured by T-Cell Levels (T-Cell Responses to HBV) |  | First dose date to end of study followed up to 24 weeks post last dose (Up to Day 225 for Cohorts 1 and 2; Up to Day 309 for Cohorts 3-8) |