Chronic Hepatitis B
Conditions
Keywords
Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis
Brief summary
This is a Phase 1 study in which healthy volunteers and participants with chronic HBV infection will receive VIR-3434 or placebo and will be assessed for safety, tolerability, pharmacokinetics (PK), and antiviral activity (only in participants with chronic HBV infection).
Interventions
BIOLOGICALVIR-3434
VIR-3434 given by subcutaneous injection or intravenous infusion.
OTHERPlacebo
Sterile normal saline (0.9% NaCl) given by subcutaneous injection or intravenous infusion.
Sponsors
Vir Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy Volunteers: Inclusion Criteria: * Male or female age 18 - 55 * Weight 40-125 kg
Exclusion criteria
* Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation * History or evidence of drug or alcohol abuse * History of allergic reactions to monoclonal antibodies or antibody fragments * History of anaphylaxis CHB Patients: Inclusion Criteria: * Male or female age 18 - 65 * Weight 40-125 kg * Chronic HBV infection for \>/= 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-emergent period, which is up to Week 24 in part A, and up to Week 8 in part B/C/D |
| Number of Participants With Clinical Laboratory Abnormalities | Up to 280 days post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUClast | Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose | VIR-3434 under the curve from time 0 to last measurable Time |
| t1/2 | Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose | VIR-3434 apparent Elimination Half-life (t1/2) in serum |
| Vz/F | Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose | VIR-3434 Volume of Distribution (SC only) |
| Vz | Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose | VIR-3434 Volume of Distribution (IV only) |
| CL/F | Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose | VIR-3434 Apparent serum clearance (SC only) |
| Tmax | Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose | VIR-3434 time of Cmax in Serum |
| Number of Participants With ADA to VIR-3434 | Part A: Up to 168 days post-dose. Parts B-D: Up to 280 days post-dose | Evaluate the immunogenicity of VIR-3434 |
| Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Parts B-D: pre-dose and 1, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose | HBsAg reductions at nadir and Week 4 |
| Part D Only: Maximum Change of HBV DNA From Baseline (Day 1 Predose) | Parts B-D: pre-dose and 1, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose Parts B-D: pre-dose and 1, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose | HBV DNA reductions at nadir and Week 4 |
| Titers (if Applicable) of ADA to VIR-3434 | Part A: Up to 168 days post-dose. Parts B-D: Up to 280 days post-dose | Evaluate the immunogenicity of VIR-3434 |
| CL | Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose | VIR-3434 Apparent serum clearance (IV only) |
| Cmax | Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose | VIR-3434 Maximum Concentration in Serum |
Countries
Germany, Hong Kong, New Zealand, Romania, Singapore, South Korea, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A: Healthy Participants 90 mg SC Healthy participants received 90 mg VIR-3434 subcutaneous | 6 |
| Part A Healthy Participants 300 mg SC Healthy participants received 300 mg VIR-3434 subcutaneous | 6 |
| Part A Healthy Participants 900 mg SC Healthy participants received 900 mg VIR-3434 subcutaneous | 6 |
| Part A Healthy Participants 900 mg IV Healthy Participants received 900 mg VIR-3434 intravenously | 6 |
| Part A: Healthy Participants 3000 mg IV Healthy participants received 3000 mg VIR-3434 intravenously | 6 |
| Part A Healthy Participants Placebo Healthy participants received placebo subcutaneously or intravenously | 11 |
| Part B: HBV Participants 6 mg SC HBV Participants on NRTI therapy with HBsAg \<3000 IU/mL received 6 mg VIR-3434 subcutaneous | 6 |
| Part B: HBV Participants 18 mg SC HBV Participants on NRTI therapy with HBsAg \<3000 IU/mL received 18 mg VIR-3434 subcutaneous | 6 |
| Part B: HBV Participants 75 mg SC HBV Participants on NRTI Therapy with HBsAg \<3000 IU/mL received 75 mg VIR-3434 subcutaneous | 6 |
| Part B: HBV Participants 300 mg SC HBV Participants on NRTI Therapy with HBsAg \<3000 IU/mL received 300 mg VIR-3434 subcutaneous | 6 |
| Part B: HBV Participants Placebo HBV Participants on NRTI Therapy with HBsAg \<3000 IU/mL received placebo subcutaneous | 8 |
| Part C: HBV Participants 18 mg SC HBV Participants on NRTI therapy with HBsAg \>/= 3000 IU/mL received 18 mg VIR-3434 subcutaneous | 6 |
| Part C: HBV Participants 75 mg SC HBV Participants on NRTI Therapy with HBsAg \>/= 3000 IU/mL received 75 mg VIR-3434 subcutaneous | 6 |
| Part C: HBV Participants 300 mg SC HBV Participants on NRTI Therapy with HBsAg \>/= 3000 IU/mL received 300 mg VIR-3434 subcutaneous | 6 |
| Part C: HBV Participants Placebo HBV Participants on NRTI Therapy with HBsAg \>/= 3000 IU/mL received placebo subcutaneous | 6 |
| Part D: HBV Participants 75 mg SC HBV Participants not on NRTI therapy with HBV DNA \>/= 1000 and any HBsAg level received 75 mg VIR-3434 subcutaneous | 6 |
| Part D: HBV Participants 300 mg SC HBV Participants not on NRTI Therapy with HBV DNA \>/= 1000 and any HBsAg level received 300 mg VIR-3434 subcutaneous | 6 |
| Part D: HBV Participants Placebo HBV Participants not on NRTI Therapy with HBV DNA \>/= 1000 IU/mL and any HBsAg level received placebo subcutaneous | 4 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part C: HBV Participants 300 mg SC | Part C: HBV Participants Placebo | Part A: Healthy Participants 90 mg SC | Part A Healthy Participants 300 mg SC | Part A Healthy Participants 900 mg SC | Part A Healthy Participants 900 mg IV | Part A: Healthy Participants 3000 mg IV | Part A Healthy Participants Placebo | Part B: HBV Participants 6 mg SC | Part B: HBV Participants 18 mg SC | Part B: HBV Participants 75 mg SC | Part B: HBV Participants 300 mg SC | Part D: HBV Participants 75 mg SC | Part B: HBV Participants Placebo | Part C: HBV Participants 18 mg SC | Part C: HBV Participants 75 mg SC | Part D: HBV Participants 300 mg SC | Part D: HBV Participants Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.8 years STANDARD_DEVIATION 8.95 | 44.0 years STANDARD_DEVIATION 8.53 | 31.3 years STANDARD_DEVIATION 11.94 | 27.7 years STANDARD_DEVIATION 7.92 | 31.5 years STANDARD_DEVIATION 9.77 | 24.8 years STANDARD_DEVIATION 4.58 | 29.3 years STANDARD_DEVIATION 12.99 | 30.3 years STANDARD_DEVIATION 10.77 | 56.3 years STANDARD_DEVIATION 5.72 | 49.0 years STANDARD_DEVIATION 6.93 | 50.8 years STANDARD_DEVIATION 8.35 | 50.0 years STANDARD_DEVIATION 8.81 | 42.7 years STANDARD_DEVIATION 7.71 | 51.6 years STANDARD_DEVIATION 6.35 | 44.5 years STANDARD_DEVIATION 10.82 | 38.2 years STANDARD_DEVIATION 8.33 | 38.0 years STANDARD_DEVIATION 6.16 | 37.3 years STANDARD_DEVIATION 8.54 | 39.6 years STANDARD_DEVIATION 12.37 |
| Baseline HbsAg (IU/mL) | 3.71 log 10 IU/mL STANDARD_DEVIATION 0.375 | 3.18 log 10 IU/mL STANDARD_DEVIATION 1.652 | — | — | — | — | — | — | 1.94 log 10 IU/mL STANDARD_DEVIATION 0.617 | 2.78 log 10 IU/mL STANDARD_DEVIATION 0.711 | 2.55 log 10 IU/mL STANDARD_DEVIATION 0.693 | 2.59 log 10 IU/mL STANDARD_DEVIATION 1.15 | 3.79 log 10 IU/mL STANDARD_DEVIATION 0.729 | 2.24 log 10 IU/mL STANDARD_DEVIATION 0.638 | 3.34 log 10 IU/mL STANDARD_DEVIATION 0.455 | 4.12 log 10 IU/mL STANDARD_DEVIATION 0.353 | 4.29 log 10 IU/mL STANDARD_DEVIATION 0.305 | 4.15 log 10 IU/mL STANDARD_DEVIATION 0.496 | 3.17 log 10 IU/mL STANDARD_DEVIATION 1.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 4 Participants | 5 Participants | 6 Participants | 9 Participants | 5 Participants | 3 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 4 Participants | 4 Participants | 5 Participants | 6 Participants | 5 Participants | 0 Participants | 2 Participants | 0 Participants | 36 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 14 Participants |
| Race (NIH/OMB) White | 6 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 2 Participants | 7 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants | 3 Participants | 2 Participants | 51 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 5 Participants | 4 Participants | 6 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 49 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants | 6 Participants | 6 Participants | 4 Participants | 5 Participants | 2 Participants | 7 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 64 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 | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 11 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 4 / 6 | 4 / 6 | 5 / 6 | 4 / 6 | 3 / 6 | 6 / 11 | 0 / 6 | 1 / 6 | 2 / 6 | 3 / 6 | 2 / 8 | 2 / 6 | 4 / 6 | 5 / 6 | 4 / 6 | 2 / 6 | 6 / 6 | 1 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 11 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 |
Outcome results
Primary
Number of Participants With Clinical Laboratory Abnormalities
Time frame: Up to 280 days post-dose
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part A: Healthy Participants 90 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 1 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 1 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 1 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 1 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 1 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 1 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 2 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 2 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 1 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 1 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 2 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 1 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 1 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 1 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 1 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 2 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 1 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 1 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 1 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 1 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 2 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 5 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 2 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 3 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 2 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 1 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 4 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 3 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 4 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT Grade 1 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 1 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 3 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST Grade 2 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Alkaline phosphatase Grade 4 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 2 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 3 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 4 | 0 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Clinical Laboratory Abnormalities | Bilirubin Grade 1 | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Treatment-emergent period, which is up to Week 24 in part A, and up to Week 8 in part B/C/D
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Healthy Participants 90 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Part A Healthy Participants Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Part B: HBV Participants Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Part C: HBV Participants Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Part D: HBV Participants 75 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Part D: HBV Participants 300 mg SC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| Part D: HBV Participants Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
Secondary
AUClast
VIR-3434 under the curve from time 0 to last measurable Time
Time frame: Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose
Population: Participants with BQL at all time points were excluded from the PK analysis, hence for different n in the cohorts. AUClast was only calculated if the PK parameter was estimated in at least 3 subjects
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | AUClast | 302 Part A: day*µg/mL | Geometric Coefficient of Variation 16 |
| Part A Healthy Participants 300 mg SC | AUClast | 964 Part A: day*µg/mL | Geometric Coefficient of Variation 22.6 |
| Part A Healthy Participants 900 mg SC | AUClast | 3060 Part A: day*µg/mL | Geometric Coefficient of Variation 19.8 |
| Part A Healthy Participants 900 mg IV | AUClast | 4010 Part A: day*µg/mL | Geometric Coefficient of Variation 28.5 |
| Part A: Healthy Participants 3000 mg IV | AUClast | 12300 Part A: day*µg/mL | Geometric Coefficient of Variation 19.7 |
Secondary
AUClast
VIR-3434 under the curve from time 0 to last measurable Time
Time frame: Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Population: Participants with BQL at all time points were excluded from the PK analysis, hence for different n in the cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | AUClast | 3130 Parts B-D: day*ng/mL | Geometric Coefficient of Variation 67.5 |
| Part A Healthy Participants 300 mg SC | AUClast | 4150 Parts B-D: day*ng/mL | Geometric Coefficient of Variation 270 |
| Part A Healthy Participants 900 mg SC | AUClast | 106000 Parts B-D: day*ng/mL | Geometric Coefficient of Variation 72.3 |
| Part A Healthy Participants 900 mg IV | AUClast | 381000 Parts B-D: day*ng/mL | Geometric Coefficient of Variation 94.2 |
| Part A: Healthy Participants 3000 mg IV | AUClast | 9540 Parts B-D: day*ng/mL | — |
| Part A Healthy Participants Placebo | AUClast | 39000 Parts B-D: day*ng/mL | Geometric Coefficient of Variation 133 |
| Part B: HBV Participants 6 mg SC | AUClast | 181,000 Parts B-D: day*ng/mL | Geometric Coefficient of Variation 964.4 |
| Part B: HBV Participants 18 mg SC | AUClast | 9,270 Parts B-D: day*ng/mL | — |
| Part B: HBV Participants 75 mg SC | AUClast | 54,300 Parts B-D: day*ng/mL | Geometric Coefficient of Variation 122.7 |
Secondary
CL
VIR-3434 Apparent serum clearance (IV only)
Time frame: Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | CL | 244 mL/day | Geometric Coefficient of Variation 19.6 |
| Part A Healthy Participants 300 mg SC | CL | 1950 mL/day | Geometric Coefficient of Variation 71.2 |
Secondary
CL/F
VIR-3434 Apparent serum clearance (SC only)
Time frame: Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | CL/F | 295 mL/day | Geometric Coefficient of Variation 16 |
| Part A Healthy Participants 300 mg SC | CL/F | 308 mL/day | Geometric Coefficient of Variation 22.7 |
| Part A Healthy Participants 900 mg SC | CL/F | 292 mL/day | Geometric Coefficient of Variation 19.7 |
| Part A Healthy Participants 900 mg IV | CL/F | 1950 mL/day | Geometric Coefficient of Variation 71.2 |
| Part A: Healthy Participants 3000 mg IV | CL/F | 496 mL/day | — |
| Part A Healthy Participants Placebo | CL/F | 697 mL/day | Geometric Coefficient of Variation 71.6 |
| Part B: HBV Participants 6 mg SC | CL/F | 653 mL/day | Geometric Coefficient of Variation 85.6 |
| Part B: HBV Participants 18 mg SC | CL/F | 1860 mL/day | — |
| Part B: HBV Participants 75 mg SC | CL/F | 1200 mL/day | Geometric Coefficient of Variation 111.2 |
| Part B: HBV Participants 300 mg SC | CL/F | 670 mL/day | Geometric Coefficient of Variation 32.8 |
| Part B: HBV Participants Placebo | CL/F | 1090 mL/day | — |
| Part C: HBV Participants 18 mg SC | CL/F | 1700 mL/day | — |
Secondary
Cmax
VIR-3434 Maximum Concentration in Serum
Time frame: Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | Cmax | 9.46 Part A: μg/mL | Geometric Coefficient of Variation 27.4 |
| Part A Healthy Participants 300 mg SC | Cmax | 32.1 Part A: μg/mL | Geometric Coefficient of Variation 18 |
| Part A Healthy Participants 900 mg SC | Cmax | 105 Part A: μg/mL | Geometric Coefficient of Variation 23.7 |
| Part A Healthy Participants 900 mg IV | Cmax | 363 Part A: μg/mL | Geometric Coefficient of Variation 32.6 |
| Part A: Healthy Participants 3000 mg IV | Cmax | 1060 Part A: μg/mL | Geometric Coefficient of Variation 20 |
Secondary
Cmax
VIR-3434 Maximum Concentration in Serum
Time frame: Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | Cmax | 352 Parts B-D: ng/mL | Geometric Coefficient of Variation 27 |
| Part A Healthy Participants 300 mg SC | Cmax | 456 Parts B-D: ng/mL | Geometric Coefficient of Variation 152.8 |
| Part A Healthy Participants 900 mg SC | Cmax | 5460 Parts B-D: ng/mL | Geometric Coefficient of Variation 36.5 |
| Part A Healthy Participants 900 mg IV | Cmax | 19700 Parts B-D: ng/mL | Geometric Coefficient of Variation 56.9 |
| Part A: Healthy Participants 3000 mg IV | Cmax | 835 Parts B-D: ng/mL | — |
| Part A Healthy Participants Placebo | Cmax | 4750 Parts B-D: ng/mL | Geometric Coefficient of Variation 46.9 |
| Part B: HBV Participants 6 mg SC | Cmax | 26100 Parts B-D: ng/mL | Geometric Coefficient of Variation 21.8 |
| Part B: HBV Participants 18 mg SC | Cmax | 6000 Parts B-D: ng/mL | Geometric Coefficient of Variation 16.8 |
| Part B: HBV Participants 75 mg SC | Cmax | 10800 Parts B-D: ng/mL | Geometric Coefficient of Variation 61.4 |
Secondary
Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose)
HBsAg reductions at nadir and Week 4
Time frame: Parts B-D: pre-dose and 1, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -1.30 IU/mL | Standard Deviation 0.152 |
| Part A: Healthy Participants 90 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -0.61 IU/mL | Standard Deviation 0.4 |
| Part A Healthy Participants 300 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -1.27 IU/mL | Standard Deviation 0.666 |
| Part A Healthy Participants 300 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -0.38 IU/mL | Standard Deviation 0.503 |
| Part A Healthy Participants 900 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -1.96 IU/mL | Standard Deviation 0.436 |
| Part A Healthy Participants 900 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -1.51 IU/mL | Standard Deviation 0.245 |
| Part A Healthy Participants 900 mg IV | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -2.24 IU/mL | Standard Deviation 0.353 |
| Part A Healthy Participants 900 mg IV | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -1.69 IU/mL | Standard Deviation 0.766 |
| Part A: Healthy Participants 3000 mg IV | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | 0.02 IU/mL | Standard Deviation 0.039 |
| Part A: Healthy Participants 3000 mg IV | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -0.04 IU/mL | Standard Deviation 0.039 |
| Part A Healthy Participants Placebo | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -1.05 IU/mL | Standard Deviation 0.598 |
| Part A Healthy Participants Placebo | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -0.30 IU/mL | Standard Deviation 0.382 |
| Part B: HBV Participants 6 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -0.16 IU/mL | Standard Deviation 0.175 |
| Part B: HBV Participants 6 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -1.28 IU/mL | Standard Deviation 0.749 |
| Part B: HBV Participants 18 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -2.17 IU/mL | Standard Deviation 0.252 |
| Part B: HBV Participants 18 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -1.43 IU/mL | Standard Deviation 0.711 |
| Part B: HBV Participants 75 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -0.06 IU/mL | Standard Deviation 0.092 |
| Part B: HBV Participants 75 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -0.01 IU/mL | Standard Deviation 0.129 |
| Part B: HBV Participants 300 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -1.77 IU/mL | Standard Deviation 0.931 |
| Part B: HBV Participants 300 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -0.48 IU/mL | Standard Deviation 0.608 |
| Part B: HBV Participants Placebo | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -0.37 IU/mL | Standard Deviation 0.368 |
| Part B: HBV Participants Placebo | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -1.83 IU/mL | Standard Deviation 0.219 |
| Part C: HBV Participants 18 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Week 4 | -0.00 IU/mL | Standard Deviation 0.016 |
| Part C: HBV Participants 18 mg SC | Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose) | Nadir | -0.09 IU/mL | Standard Deviation 0.039 |
Secondary
Number of Participants With ADA to VIR-3434
Evaluate the immunogenicity of VIR-3434
Time frame: Part A: Up to 168 days post-dose. Parts B-D: Up to 280 days post-dose
Population: Immunogenicity Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Healthy Participants 90 mg SC | Number of Participants With ADA to VIR-3434 | 0 Participants |
| Part A Healthy Participants 300 mg SC | Number of Participants With ADA to VIR-3434 | 1 Participants |
| Part A Healthy Participants 900 mg SC | Number of Participants With ADA to VIR-3434 | 1 Participants |
| Part A Healthy Participants 900 mg IV | Number of Participants With ADA to VIR-3434 | 0 Participants |
| Part A: Healthy Participants 3000 mg IV | Number of Participants With ADA to VIR-3434 | 0 Participants |
| Part A Healthy Participants Placebo | Number of Participants With ADA to VIR-3434 | 0 Participants |
| Part B: HBV Participants 6 mg SC | Number of Participants With ADA to VIR-3434 | 1 Participants |
| Part B: HBV Participants 18 mg SC | Number of Participants With ADA to VIR-3434 | 1 Participants |
| Part B: HBV Participants 75 mg SC | Number of Participants With ADA to VIR-3434 | 2 Participants |
| Part B: HBV Participants 300 mg SC | Number of Participants With ADA to VIR-3434 | 2 Participants |
| Part B: HBV Participants Placebo | Number of Participants With ADA to VIR-3434 | 1 Participants |
| Part C: HBV Participants 18 mg SC | Number of Participants With ADA to VIR-3434 | 2 Participants |
| Part C: HBV Participants 75 mg SC | Number of Participants With ADA to VIR-3434 | 4 Participants |
| Part C: HBV Participants 300 mg SC | Number of Participants With ADA to VIR-3434 | 1 Participants |
Secondary
Part D Only: Maximum Change of HBV DNA From Baseline (Day 1 Predose)
HBV DNA reductions at nadir and Week 4
Time frame: Parts B-D: pre-dose and 1, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose Parts B-D: pre-dose and 1, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | Part D Only: Maximum Change of HBV DNA From Baseline (Day 1 Predose) | Nadir | -1.44 IU/mL | Standard Deviation 0.998 |
| Part A: Healthy Participants 90 mg SC | Part D Only: Maximum Change of HBV DNA From Baseline (Day 1 Predose) | Week 4 | -0.70 IU/mL | Standard Deviation 0.917 |
| Part A Healthy Participants 300 mg SC | Part D Only: Maximum Change of HBV DNA From Baseline (Day 1 Predose) | Nadir | -2.07 IU/mL | Standard Deviation 1.007 |
| Part A Healthy Participants 300 mg SC | Part D Only: Maximum Change of HBV DNA From Baseline (Day 1 Predose) | Week 4 | -0.61 IU/mL | Standard Deviation 1.195 |
| Part A Healthy Participants 900 mg SC | Part D Only: Maximum Change of HBV DNA From Baseline (Day 1 Predose) | Nadir | -0.12 IU/mL | Standard Deviation 0.06 |
| Part A Healthy Participants 900 mg SC | Part D Only: Maximum Change of HBV DNA From Baseline (Day 1 Predose) | Week 4 | 0.06 IU/mL | Standard Deviation 0.472 |
Secondary
t1/2
VIR-3434 apparent Elimination Half-life (t1/2) in serum
Time frame: Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Population: PK Anal;ysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Healthy Participants 90 mg SC | t1/2 | 28.5 day |
| Part A Healthy Participants 300 mg SC | t1/2 | 24.3 day |
| Part A Healthy Participants 900 mg SC | t1/2 | 25.2 day |
| Part A Healthy Participants 900 mg IV | t1/2 | 24.0 day |
| Part A: Healthy Participants 3000 mg IV | t1/2 | 20.7 day |
| Part A Healthy Participants Placebo | t1/2 | 3.57 day |
| Part B: HBV Participants 6 mg SC | t1/2 | 6.34 day |
| Part B: HBV Participants 18 mg SC | t1/2 | 7.94 day |
| Part B: HBV Participants 75 mg SC | t1/2 | 13.6 day |
| Part B: HBV Participants 300 mg SC | t1/2 | 3.82 day |
| Part B: HBV Participants Placebo | t1/2 | 4.25 day |
| Part C: HBV Participants 18 mg SC | t1/2 | 8.36 day |
| Part C: HBV Participants 75 mg SC | t1/2 | 3.17 day |
| Part C: HBV Participants 300 mg SC | t1/2 | 1.99 day |
Secondary
Titers (if Applicable) of ADA to VIR-3434
Evaluate the immunogenicity of VIR-3434
Time frame: Part A: Up to 168 days post-dose. Parts B-D: Up to 280 days post-dose
Population: Immunogenicity Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Healthy Participants 90 mg SC | Titers (if Applicable) of ADA to VIR-3434 | 0 Median Titer |
| Part A Healthy Participants 300 mg SC | Titers (if Applicable) of ADA to VIR-3434 | 20 Median Titer |
| Part A Healthy Participants 900 mg SC | Titers (if Applicable) of ADA to VIR-3434 | 160 Median Titer |
| Part A Healthy Participants 900 mg IV | Titers (if Applicable) of ADA to VIR-3434 | 0 Median Titer |
| Part A: Healthy Participants 3000 mg IV | Titers (if Applicable) of ADA to VIR-3434 | 0 Median Titer |
| Part A Healthy Participants Placebo | Titers (if Applicable) of ADA to VIR-3434 | 0 Median Titer |
| Part B: HBV Participants 6 mg SC | Titers (if Applicable) of ADA to VIR-3434 | 40 Median Titer |
| Part B: HBV Participants 18 mg SC | Titers (if Applicable) of ADA to VIR-3434 | 80 Median Titer |
| Part B: HBV Participants 75 mg SC | Titers (if Applicable) of ADA to VIR-3434 | 240 Median Titer |
| Part B: HBV Participants 300 mg SC | Titers (if Applicable) of ADA to VIR-3434 | 120 Median Titer |
| Part B: HBV Participants Placebo | Titers (if Applicable) of ADA to VIR-3434 | 80 Median Titer |
| Part C: HBV Participants 18 mg SC | Titers (if Applicable) of ADA to VIR-3434 | 20 Median Titer |
| Part C: HBV Participants 75 mg SC | Titers (if Applicable) of ADA to VIR-3434 | 40 Median Titer |
| Part C: HBV Participants 300 mg SC | Titers (if Applicable) of ADA to VIR-3434 | 20 Median Titer |
Secondary
Tmax
VIR-3434 time of Cmax in Serum
Time frame: Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Population: Participants with BQL at all time points were excluded from the PK analysis, hence for different n in the cohorts. CV was only calculated if the PK parameter was estimated in at least 3 subjects
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Healthy Participants 90 mg SC | Tmax | 7.00 day |
| Part A Healthy Participants 300 mg SC | Tmax | 7 day |
| Part A Healthy Participants 900 mg SC | Tmax | 3 day |
| Part A Healthy Participants 900 mg IV | Tmax | .0833 day |
| Part A: Healthy Participants 3000 mg IV | Tmax | .0833 day |
| Part A Healthy Participants Placebo | Tmax | 6.90 day |
| Part B: HBV Participants 6 mg SC | Tmax | 2.92 day |
| Part B: HBV Participants 18 mg SC | Tmax | 5.44 day |
| Part B: HBV Participants 75 mg SC | Tmax | 2.96 day |
| Part B: HBV Participants 300 mg SC | Tmax | 3.98 day |
| Part B: HBV Participants Placebo | Tmax | 3.00 day |
| Part C: HBV Participants 18 mg SC | Tmax | 2.99 day |
| Part C: HBV Participants 75 mg SC | Tmax | 4.08 day |
| Part C: HBV Participants 300 mg SC | Tmax | 2.99 day |
Secondary
Vz
VIR-3434 Volume of Distribution (IV only)
Time frame: Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | Vz | 7620 mL | Geometric Coefficient of Variation 26.3 |
| Part A Healthy Participants 300 mg SC | Vz | 7290 mL | Geometric Coefficient of Variation 24.6 |
Secondary
Vz/F
VIR-3434 Volume of Distribution (SC only)
Time frame: Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Healthy Participants 90 mg SC | Vz/F | 12200 mL | Geometric Coefficient of Variation 15.2 |
| Part A Healthy Participants 300 mg SC | Vz/F | 10900 mL | Geometric Coefficient of Variation 27.3 |
| Part A Healthy Participants 900 mg SC | Vz/F | 10600 mL | Geometric Coefficient of Variation 27.7 |
| Part A Healthy Participants 900 mg IV | Vz/F | 9420 mL | Geometric Coefficient of Variation 12.9 |
| Part A: Healthy Participants 3000 mg IV | Vz/F | 4540 mL | — |
| Part A Healthy Participants Placebo | Vz/F | 7410 mL | Geometric Coefficient of Variation 21.5 |
| Part B: HBV Participants 6 mg SC | Vz/F | 9830 mL | Geometric Coefficient of Variation 54.2 |
| Part B: HBV Participants 18 mg SC | Vz/F | 10300 mL | — |
| Part B: HBV Participants 75 mg SC | Vz/F | 6710 mL | Geometric Coefficient of Variation 27.4 |
| Part B: HBV Participants 300 mg SC | Vz/F | 7330 mL | Geometric Coefficient of Variation 22.5 |
| Part B: HBV Participants Placebo | Vz/F | 5000 mL | — |
| Part C: HBV Participants 18 mg SC | Vz/F | 4880 mL | — |