Hepatitis B, Chronic
Conditions
Keywords
Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis
Brief summary
This study is to evaluate the safety, pharmacokinetics characteristics, and antiviral activities of multiple doses of VIR-2218 in adults with chronic HBV infection in mainland China.
Interventions
DRUGVIR-2218
VIR-2218 given by subcutaneous injection
DRUGPlacebo
Saline given by subcutaneous injection
Sponsors
Vir Biotechnology, Inc.
Alnylam Pharmaceuticals
Brii Biosciences Limited
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
No
Inclusion criteria
* Male or female age 18 - 65; * Weight ≥ 40 kg to ≤ 125 kg; * Chronic HBV infection as defined by a positive serum HBsAg for ≥ 6 months;
Exclusion criteria
* Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation; * Significant fibrosis or cirrhosis; * History or evidence of drug or alcohol abuse; * History of intolerance to SC injection; * History of chronic liver disease from any cause other than chronic HBV infection; * History of hepatic decompensation;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-emergent Adverse Events (TEAEs) | up to 48 weeks | Number of participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0 are summarized by cohort. Incidence is defined as the number of participants with TEAEs in relation to the total number of participants in the cohort. TEAEs are defined as any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug. |
| Clinical Assessments Including But Not Limited to Laboratory Test Results | up to 48 weeks | Number of participants with graded hematology, coagulation, chemistry abnormalities, and clinically significant abnormalities in vital signs and ECGs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Maximum Plasma Concentration | Maximum plasma concentrations were calculated based on all above results for Day 1 and Day 29 (Week 4). | VIR-2218 and metabolite maximum plasma concentrations (ng/mL) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24. |
| PK: Time to Reach Maximum Plasma Concentration | Time to Cmax were calculated based on all above results for Day 1 and Day 29 (Week 4). | VIR-2218 and metabolite time to Cmax (h) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24. |
| PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | Area under the curve were calculated based on all above results for Day 1 and Day 29 (Week 4). | VIR-2218 and metabolite area under the curve from time 0 to last measurable time (ng\*h/mL) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24. |
| PK: Area Under the Plasma Concentration Versus Time Curve to Infinity | Area under the curve were calculated based on all above results for Day 1 and Day 29 (Week 4). | VIR-2218 and metabolite area under the curve from time 0 to infinity (ng\*h/mL) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24. |
| PK: Percent of Area Extrapolated From AUC Last to Infinity | Percent of area extrapolated from AUC last to infinity were calculated based on all above results for Day 1 and Day 29 (Week 4). | VIR-2218 and metabolite percent of area extrapolated from AUC last to infinity (%) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24. |
| Number of Participants With Sustained Serum HBsAg Loss for at Least 6 Months | up to 48 weeks | Number of participants with sustained serum HBsAg \< 0.05 IU/mL at all visits for at least 6 months |
| PK: Apparent Plasma Clearance | Apparent plasma clearance were calculated based on all above results for Day 1 and Day 29 (Week 4). | VIR-2218 and metabolite apparent plasma clearance CL/F (mL/h) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24. |
| PK: Apparent Volume of Distribution | Apparent volume of distribution were calculated based on all above results for Day 1 and Day 29 (Week 4). | VIR-2218 and metabolite apparent volume of distribution Vz/F (mL) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24. |
| Maximum Change of Serum HBsAg From Baseline | up to 16 weeks | Maximum change of serum HBsAg from Day 1 until 12 weeks post last dose (negative values mean reductions from baseline, positive values mean increased from baseline) |
| Number of Participants With Serum HBsAg Loss | up to 48 weeks | Number of participants with serum HBsAg \< 0.05 IU/mL at two or more consecutive measurements |
| For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | up to 48 weeks | HBeAg loss is defined as quantitative HBeAg \< 0.14 IU/mL at two or more consecutive measurements. Anti-HBe seroconversion is defined as anti-HBe positivity at two or more consecutive measurements. |
| PK: Apparent Terminal Elimination Half-life | Apparent terminal elimination half-life were calculated based on all above results for Day 1 and Day 29 (Week 4). | VIR-2218 and metabolite apparent terminal elimination half-life (h) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24. |
| Number of Participants With Anti-HBs Seroconversion at Any Timepoint | up to 48 weeks | Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: VIR-2218 50 mg HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart | 4 |
| Part 1: VIR-2218 100 mg HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart | 4 |
| Part 1: Placebo HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart | 3 |
| Part 2: VIR-2218 50 mg HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart | 4 |
| Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart | 4 |
| Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart | 2 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1: VIR-2218 50 mg | Part 1: VIR-2218 100 mg | Part 1: Placebo | Part 2: VIR-2218 50 mg | Part 2: VIR-2218 100 mg | Part 2: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 48.5 years STANDARD_DEVIATION 9.68 | 36.5 years STANDARD_DEVIATION 9.26 | 31.0 years STANDARD_DEVIATION 5.2 | 41.8 years STANDARD_DEVIATION 4.27 | 39.5 years STANDARD_DEVIATION 10.66 | 38.0 years STANDARD_DEVIATION 11.31 | 39.7 years STANDARD_DEVIATION 9.26 |
| Baseline log10 hepatitis B surface antigen | 2.815 log10 IU/mL STANDARD_DEVIATION 0.4865 | 3.278 log10 IU/mL STANDARD_DEVIATION 0.791 | 2.948 log10 IU/mL STANDARD_DEVIATION 0.4822 | 3.598 log10 IU/mL STANDARD_DEVIATION 0.5479 | 3.243 log10 IU/mL STANDARD_DEVIATION 0.4848 | 3.722 log10 IU/mL STANDARD_DEVIATION 0.0729 | 3.239 log10 IU/mL STANDARD_DEVIATION 0.5756 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 4 participants | 4 participants | 3 participants | 4 participants | 4 participants | 2 participants | 21 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 18 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 4 | 0 / 2 |
| other Total, other adverse events | 1 / 4 | 2 / 4 | 0 / 3 | 2 / 4 | 1 / 4 | 1 / 2 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 4 | 0 / 2 |
Outcome results
Primary
Clinical Assessments Including But Not Limited to Laboratory Test Results
Number of participants with graded hematology, coagulation, chemistry abnormalities, and clinically significant abnormalities in vital signs and ECGs
Time frame: up to 48 weeks
Population: All randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 1 | 4 Participants |
| Part 1: VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 2 or above | 0 Participants |
| Part 1: VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant vital signs | 0 Participants |
| Part 1: VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant ECGs | 0 Participants |
| Part 1: VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant vital signs | 0 Participants |
| Part 1: VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 2 or above | 0 Participants |
| Part 1: VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 1 | 4 Participants |
| Part 1: VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant ECGs | 0 Participants |
| Part 1: Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant ECGs | 0 Participants |
| Part 1: Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant vital signs | 0 Participants |
| Part 1: Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 2 or above | 0 Participants |
| Part 1: Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 1 | 2 Participants |
| Part 2: VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 1 | 2 Participants |
| Part 2: VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant ECGs | 0 Participants |
| Part 2: VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 2 or above | 0 Participants |
| Part 2: VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant vital signs | 0 Participants |
| Part 2: VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant vital signs | 0 Participants |
| Part 2: VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant ECGs | 0 Participants |
| Part 2: VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 2 or above | 0 Participants |
| Part 2: VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 1 | 4 Participants |
| Part 2: Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 2 or above | 0 Participants |
| Part 2: Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant vital signs | 0 Participants |
| Part 2: Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any clinically significant ECGs | 0 Participants |
| Part 2: Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Any post baseline laboratory abnormalities of CTCAE Grade 1 | 2 Participants |
Primary
Incidence of Treatment-emergent Adverse Events (TEAEs)
Number of participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0 are summarized by cohort. Incidence is defined as the number of participants with TEAEs in relation to the total number of participants in the cohort. TEAEs are defined as any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug.
Time frame: up to 48 weeks
Population: All randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 1 | 0 Participants |
| Part 1: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| Part 1: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 2 | 1 Participants |
| Part 1: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any drug related TEAEs | 0 Participants |
| Part 1: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 3 or above | 0 Participants |
| Part 1: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 1 Participants |
| Part 1: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 2 Participants |
| Part 1: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| Part 1: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 1 | 1 Participants |
| Part 1: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 2 | 1 Participants |
| Part 1: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 3 or above | 0 Participants |
| Part 1: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any drug related TEAEs | 0 Participants |
| Part 1: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 0 Participants |
| Part 1: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 1 | 0 Participants |
| Part 1: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 2 | 0 Participants |
| Part 1: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 3 or above | 0 Participants |
| Part 1: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| Part 1: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any drug related TEAEs | 0 Participants |
| Part 2: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 2 Participants |
| Part 2: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 1 | 2 Participants |
| Part 2: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 3 or above | 0 Participants |
| Part 2: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| Part 2: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any drug related TEAEs | 1 Participants |
| Part 2: VIR-2218 50 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 2 | 0 Participants |
| Part 2: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 3 or above | 0 Participants |
| Part 2: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| Part 2: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any drug related TEAEs | 1 Participants |
| Part 2: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 1 | 1 Participants |
| Part 2: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 2 | 0 Participants |
| Part 2: VIR-2218 100 mg | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 1 Participants |
| Part 2: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| Part 2: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 1 Participants |
| Part 2: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 1 | 1 Participants |
| Part 2: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 2 | 0 Participants |
| Part 2: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs of CTCAE Grade 3 or above | 0 Participants |
| Part 2: Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any drug related TEAEs | 0 Participants |
Secondary
For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint
HBeAg loss is defined as quantitative HBeAg \< 0.14 IU/mL at two or more consecutive measurements. Anti-HBe seroconversion is defined as anti-HBe positivity at two or more consecutive measurements.
Time frame: up to 48 weeks
Population: Part 2 (HBeAg positive) participants only; all randomized participants who received at least 1 dose of study drug and had at least 1 non-missing data for antiviral activity parameter
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: VIR-2218 50 mg | For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | HBeAg loss | 0 Participants |
| Part 1: VIR-2218 50 mg | For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | Anti-HBe seroconversion | 0 Participants |
| Part 1: VIR-2218 100 mg | For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | HBeAg loss | 0 Participants |
| Part 1: VIR-2218 100 mg | For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | Anti-HBe seroconversion | 0 Participants |
| Part 1: Placebo | For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | HBeAg loss | 0 Participants |
| Part 1: Placebo | For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | Anti-HBe seroconversion | 0 Participants |
Secondary
Maximum Change of Serum HBsAg From Baseline
Maximum change of serum HBsAg from Day 1 until 12 weeks post last dose (negative values mean reductions from baseline, positive values mean increased from baseline)
Time frame: up to 16 weeks
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 non-missing data for antiviral parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: VIR-2218 50 mg | Maximum Change of Serum HBsAg From Baseline | -1.064 log10 IU/mL | Standard Deviation 0.1047 |
| Part 1: VIR-2218 100 mg | Maximum Change of Serum HBsAg From Baseline | -1.346 log10 IU/mL | Standard Deviation 0.5169 |
| Part 1: Placebo | Maximum Change of Serum HBsAg From Baseline | -0.049 log10 IU/mL | Standard Deviation 0.0158 |
| Part 2: VIR-2218 50 mg | Maximum Change of Serum HBsAg From Baseline | -0.793 log10 IU/mL | Standard Deviation 0.1017 |
| Part 2: VIR-2218 100 mg | Maximum Change of Serum HBsAg From Baseline | -1.268 log10 IU/mL | Standard Deviation 0.1693 |
| Part 2: Placebo | Maximum Change of Serum HBsAg From Baseline | -0.120 log10 IU/mL | Standard Deviation 0.0826 |
Secondary
Number of Participants With Anti-HBs Seroconversion at Any Timepoint
Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements
Time frame: up to 48 weeks
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 non-missing data for antiviral activity parameter
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: VIR-2218 50 mg | Number of Participants With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part 1: VIR-2218 100 mg | Number of Participants With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part 1: Placebo | Number of Participants With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part 2: VIR-2218 50 mg | Number of Participants With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part 2: VIR-2218 100 mg | Number of Participants With Anti-HBs Seroconversion at Any Timepoint | 1 Participants |
| Part 2: Placebo | Number of Participants With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
Secondary
Number of Participants With Serum HBsAg Loss
Number of participants with serum HBsAg \< 0.05 IU/mL at two or more consecutive measurements
Time frame: up to 48 weeks
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 non-missing data for antiviral parameters
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: VIR-2218 50 mg | Number of Participants With Serum HBsAg Loss | 0 Participants |
| Part 1: VIR-2218 100 mg | Number of Participants With Serum HBsAg Loss | 0 Participants |
| Part 1: Placebo | Number of Participants With Serum HBsAg Loss | 0 Participants |
| Part 2: VIR-2218 50 mg | Number of Participants With Serum HBsAg Loss | 0 Participants |
| Part 2: VIR-2218 100 mg | Number of Participants With Serum HBsAg Loss | 0 Participants |
| Part 2: Placebo | Number of Participants With Serum HBsAg Loss | 0 Participants |
Secondary
Number of Participants With Sustained Serum HBsAg Loss for at Least 6 Months
Number of participants with sustained serum HBsAg \< 0.05 IU/mL at all visits for at least 6 months
Time frame: up to 48 weeks
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 non-missing data for antiviral parameters
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: VIR-2218 50 mg | Number of Participants With Sustained Serum HBsAg Loss for at Least 6 Months | 0 Participants |
| Part 1: VIR-2218 100 mg | Number of Participants With Sustained Serum HBsAg Loss for at Least 6 Months | 0 Participants |
| Part 1: Placebo | Number of Participants With Sustained Serum HBsAg Loss for at Least 6 Months | 0 Participants |
| Part 2: VIR-2218 50 mg | Number of Participants With Sustained Serum HBsAg Loss for at Least 6 Months | 0 Participants |
| Part 2: VIR-2218 100 mg | Number of Participants With Sustained Serum HBsAg Loss for at Least 6 Months | 0 Participants |
| Part 2: Placebo | Number of Participants With Sustained Serum HBsAg Loss for at Least 6 Months | 0 Participants |
Secondary
PK: Apparent Plasma Clearance
VIR-2218 and metabolite apparent plasma clearance CL/F (mL/h) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.
Time frame: Apparent plasma clearance were calculated based on all above results for Day 1 and Day 29 (Week 4).
Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: VIR-2218 100 mg | PK: Apparent Plasma Clearance | VIR-2218 CL/F (Day 1) | 35400 mL/h | Geometric Coefficient of Variation 16.7 |
| Part 1: VIR-2218 100 mg | PK: Apparent Plasma Clearance | VIR-2218 CL/F (Day 29) | 39000 mL/h | — |
| Part 1: Placebo | PK: Apparent Plasma Clearance | VIR-2218 CL/F (Day 29) | 41300 mL/h | — |
| Part 2: VIR-2218 50 mg | PK: Apparent Plasma Clearance | VIR-2218 CL/F (Day 29) | 28300 mL/h | — |
Secondary
PK: Apparent Terminal Elimination Half-life
VIR-2218 and metabolite apparent terminal elimination half-life (h) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.
Time frame: Apparent terminal elimination half-life were calculated based on all above results for Day 1 and Day 29 (Week 4).
Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: VIR-2218 100 mg | PK: Apparent Terminal Elimination Half-life | VIR-2218 t1/2 (Day 1) | 4.16 hour |
| Part 1: VIR-2218 100 mg | PK: Apparent Terminal Elimination Half-life | VIR-2218 t1/2 (Day 29) | 7.66 hour |
| Part 1: Placebo | PK: Apparent Terminal Elimination Half-life | VIR-2218 t1/2 (Day 29) | 6.53 hour |
| Part 2: VIR-2218 50 mg | PK: Apparent Terminal Elimination Half-life | VIR-2218 t1/2 (Day 29) | 5.49 hour |
Secondary
PK: Apparent Volume of Distribution
VIR-2218 and metabolite apparent volume of distribution Vz/F (mL) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.
Time frame: Apparent volume of distribution were calculated based on all above results for Day 1 and Day 29 (Week 4).
Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: VIR-2218 100 mg | PK: Apparent Volume of Distribution | VIR-2218 Vz/F (Day 1) | 213000 mL | Geometric Coefficient of Variation 18.6 |
| Part 1: VIR-2218 100 mg | PK: Apparent Volume of Distribution | VIR-2218 Vz/F (Day 29) | 431000 mL | — |
| Part 1: Placebo | PK: Apparent Volume of Distribution | VIR-2218 Vz/F (Day 29) | 389000 mL | — |
| Part 2: VIR-2218 50 mg | PK: Apparent Volume of Distribution | VIR-2218 Vz/F (Day 29) | 224000 mL | — |
Secondary
PK: Area Under the Plasma Concentration Versus Time Curve to Infinity
VIR-2218 and metabolite area under the curve from time 0 to infinity (ng\*h/mL) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.
Time frame: Area under the curve were calculated based on all above results for Day 1 and Day 29 (Week 4).
Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: VIR-2218 100 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Infinity | VIR-2218 AUCinf (Day 1) | 2820 ng*h/mL | Geometric Coefficient of Variation 16.7 |
| Part 1: VIR-2218 100 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Infinity | VIR-2218 AUCinf (Day 29) | 2570 ng*h/mL | — |
| Part 1: Placebo | PK: Area Under the Plasma Concentration Versus Time Curve to Infinity | VIR-2218 AUCinf (Day 29) | 1210 ng*h/mL | — |
| Part 2: VIR-2218 50 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Infinity | VIR-2218 AUCinf (Day 29) | 3530 ng*h/mL | — |
Secondary
PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint
VIR-2218 and metabolite area under the curve from time 0 to last measurable time (ng\*h/mL) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.
Time frame: Area under the curve were calculated based on all above results for Day 1 and Day 29 (Week 4).
Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: VIR-2218 50 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | VIR-2218 AUClast (Day 1) | 1080 ng*h/mL | Geometric Coefficient of Variation 25.3 |
| Part 1: VIR-2218 50 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | VIR-2218 AUClast (Day 29) | 854 ng*h/mL | Geometric Coefficient of Variation 34.2 |
| Part 1: VIR-2218 50 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | AS(N-1)3'VIR-2218 AUClast (Day 1) | 58.7 ng*h/mL | Geometric Coefficient of Variation 28.9 |
| Part 1: VIR-2218 50 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | AS(N-1)3'VIR-2218 AUClast (Day 29) | 50.2 ng*h/mL | Geometric Coefficient of Variation 52.5 |
| Part 1: VIR-2218 100 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | VIR-2218 AUClast (Day 29) | 2390 ng*h/mL | Geometric Coefficient of Variation 26.6 |
| Part 1: VIR-2218 100 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | AS(N-1)3'VIR-2218 AUClast (Day 1) | 159 ng*h/mL | Geometric Coefficient of Variation 30.5 |
| Part 1: VIR-2218 100 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | AS(N-1)3'VIR-2218 AUClast (Day 29) | 140 ng*h/mL | Geometric Coefficient of Variation 81.2 |
| Part 1: VIR-2218 100 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | VIR-2218 AUClast (Day 1) | 1400 ng*h/mL | Geometric Coefficient of Variation 115.6 |
| Part 1: Placebo | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | AS(N-1)3'VIR-2218 AUClast (Day 1) | 67.6 ng*h/mL | Geometric Coefficient of Variation 2.1 |
| Part 1: Placebo | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | VIR-2218 AUClast (Day 29) | 580 ng*h/mL | Geometric Coefficient of Variation 56.9 |
| Part 1: Placebo | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | AS(N-1)3'VIR-2218 AUClast (Day 29) | 63.1 ng*h/mL | Geometric Coefficient of Variation 6.1 |
| Part 1: Placebo | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | VIR-2218 AUClast (Day 1) | 626 ng*h/mL | Geometric Coefficient of Variation 31.1 |
| Part 2: VIR-2218 50 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | AS(N-1)3'VIR-2218 AUClast (Day 29) | 155 ng*h/mL | Geometric Coefficient of Variation 39.8 |
| Part 2: VIR-2218 50 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | VIR-2218 AUClast (Day 29) | 3140 ng*h/mL | Geometric Coefficient of Variation 15.8 |
| Part 2: VIR-2218 50 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | VIR-2218 AUClast (Day 1) | 3190 ng*h/mL | Geometric Coefficient of Variation 42.3 |
| Part 2: VIR-2218 50 mg | PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint | AS(N-1)3'VIR-2218 AUClast (Day 1) | 180 ng*h/mL | Geometric Coefficient of Variation 63.4 |
Secondary
PK: Maximum Plasma Concentration
VIR-2218 and metabolite maximum plasma concentrations (ng/mL) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.
Time frame: Maximum plasma concentrations were calculated based on all above results for Day 1 and Day 29 (Week 4).
Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: VIR-2218 50 mg | PK: Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Cmax (Day 1) | 10.2 ng/mL | — |
| Part 1: VIR-2218 50 mg | PK: Maximum Plasma Concentration | VIR-2218 Cmax (Day 29) | 125 ng/mL | Geometric Coefficient of Variation 48.8 |
| Part 1: VIR-2218 50 mg | PK: Maximum Plasma Concentration | VIR-2218 Cmax (Day 1) | 120 ng/mL | Geometric Coefficient of Variation 40.5 |
| Part 1: VIR-2218 50 mg | PK: Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Cmax (Day 29) | 16.3 ng/mL | — |
| Part 1: VIR-2218 100 mg | PK: Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Cmax (Day 1) | 31.4 ng/mL | — |
| Part 1: VIR-2218 100 mg | PK: Maximum Plasma Concentration | VIR-2218 Cmax (Day 1) | 144 ng/mL | Geometric Coefficient of Variation 100.5 |
| Part 1: VIR-2218 100 mg | PK: Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Cmax (Day 29) | 23.6 ng/mL | Geometric Coefficient of Variation 48.8 |
| Part 1: VIR-2218 100 mg | PK: Maximum Plasma Concentration | VIR-2218 Cmax (Day 29) | 198 ng/mL | Geometric Coefficient of Variation 52.9 |
| Part 1: Placebo | PK: Maximum Plasma Concentration | VIR-2218 Cmax (Day 29) | 76.5 ng/mL | Geometric Coefficient of Variation 35.7 |
| Part 1: Placebo | PK: Maximum Plasma Concentration | VIR-2218 Cmax (Day 1) | 65.8 ng/mL | Geometric Coefficient of Variation 58.6 |
| Part 1: Placebo | PK: Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Cmax (Day 29) | 9.75 ng/mL | Geometric Coefficient of Variation 1.1 |
| Part 2: VIR-2218 50 mg | PK: Maximum Plasma Concentration | VIR-2218 Cmax (Day 29) | 268 ng/mL | Geometric Coefficient of Variation 43 |
| Part 2: VIR-2218 50 mg | PK: Maximum Plasma Concentration | VIR-2218 Cmax (Day 1) | 260 ng/mL | Geometric Coefficient of Variation 90.4 |
| Part 2: VIR-2218 50 mg | PK: Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Cmax (Day 29) | 19.3 ng/mL | Geometric Coefficient of Variation 82.1 |
| Part 2: VIR-2218 50 mg | PK: Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Cmax (Day 1) | 28.1 ng/mL | Geometric Coefficient of Variation 171.1 |
Secondary
PK: Percent of Area Extrapolated From AUC Last to Infinity
VIR-2218 and metabolite percent of area extrapolated from AUC last to infinity (%) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.
Time frame: Percent of area extrapolated from AUC last to infinity were calculated based on all above results for Day 1 and Day 29 (Week 4).
Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: VIR-2218 50 mg | PK: Percent of Area Extrapolated From AUC Last to Infinity | VIR-2218 %AUCextrap (Day 29) | 46.2 % of AUCinf | — |
| Part 1: VIR-2218 100 mg | PK: Percent of Area Extrapolated From AUC Last to Infinity | VIR-2218 %AUCextrap (Day 1) | 2.69 % of AUCinf | Geometric Coefficient of Variation 5.1 |
| Part 1: VIR-2218 100 mg | PK: Percent of Area Extrapolated From AUC Last to Infinity | VIR-2218 %AUCextrap (Day 29) | 13.8 % of AUCinf | — |
| Part 1: VIR-2218 100 mg | PK: Percent of Area Extrapolated From AUC Last to Infinity | AS(N-1)3'VIR-2218 %AUCextrap (Day 29) | 49.2 % of AUCinf | — |
| Part 1: Placebo | PK: Percent of Area Extrapolated From AUC Last to Infinity | VIR-2218 %AUCextrap (Day 29) | 23.9 % of AUCinf | Geometric Coefficient of Variation 263.4 |
| Part 2: VIR-2218 50 mg | PK: Percent of Area Extrapolated From AUC Last to Infinity | VIR-2218 %AUCextrap (Day 29) | 5.88 % of AUCinf | — |
Secondary
PK: Time to Reach Maximum Plasma Concentration
VIR-2218 and metabolite time to Cmax (h) VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.
Time frame: Time to Cmax were calculated based on all above results for Day 1 and Day 29 (Week 4).
Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: VIR-2218 50 mg | PK: Time to Reach Maximum Plasma Concentration | VIR-2218 Tmax (Day 1) | 4.99 hour |
| Part 1: VIR-2218 50 mg | PK: Time to Reach Maximum Plasma Concentration | VIR-2218 Tmax (Day 29) | 7.76 hour |
| Part 1: VIR-2218 50 mg | PK: Time to Reach Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Tmax (Day 1) | 7.95 hour |
| Part 1: VIR-2218 50 mg | PK: Time to Reach Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Tmax (Day 29) | 7.76 hour |
| Part 1: VIR-2218 100 mg | PK: Time to Reach Maximum Plasma Concentration | VIR-2218 Tmax (Day 29) | 4.02 hour |
| Part 1: VIR-2218 100 mg | PK: Time to Reach Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Tmax (Day 1) | 4.98 hour |
| Part 1: VIR-2218 100 mg | PK: Time to Reach Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Tmax (Day 29) | 5.93 hour |
| Part 1: VIR-2218 100 mg | PK: Time to Reach Maximum Plasma Concentration | VIR-2218 Tmax (Day 1) | 2.00 hour |
| Part 1: Placebo | PK: Time to Reach Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Tmax (Day 1) | 7.80 hour |
| Part 1: Placebo | PK: Time to Reach Maximum Plasma Concentration | VIR-2218 Tmax (Day 29) | 2.50 hour |
| Part 1: Placebo | PK: Time to Reach Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Tmax (Day 29) | 4.00 hour |
| Part 1: Placebo | PK: Time to Reach Maximum Plasma Concentration | VIR-2218 Tmax (Day 1) | 4.02 hour |
| Part 2: VIR-2218 50 mg | PK: Time to Reach Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Tmax (Day 29) | 5.93 hour |
| Part 2: VIR-2218 50 mg | PK: Time to Reach Maximum Plasma Concentration | VIR-2218 Tmax (Day 29) | 5.93 hour |
| Part 2: VIR-2218 50 mg | PK: Time to Reach Maximum Plasma Concentration | VIR-2218 Tmax (Day 1) | 4.00 hour |
| Part 2: VIR-2218 50 mg | PK: Time to Reach Maximum Plasma Concentration | AS(N-1)3'VIR-2218 Tmax (Day 1) | 5.79 hour |