Chronic Hepatitis B
Conditions
Keywords
Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis
Brief summary
This is a phase 1/2 study in which healthy adult subjects and subjects with chronic hepatitis B virus (HBV) infection will receive VIR-2218 or placebo and will be assessed for safety, tolerability, pharmacokinetics, and antiviral activity (only in subjects with chronic HBV). In the single ascending dose (SAD) part, Part A, healthy adult subjects will receive one dose of VIR-2218 or placebo, administered subcutaneously (SC). In the multiple ascending dose (MAD) parts, Part B & Part C, subjects with chronic HBV infection will receive two doses of VIR-2218 or placebo every 4 weeks administered SC.
Interventions
DRUGVIR-2218
VIR-2218 given by subcutaneous injection
DRUGPlacebo
Sterile normal saline (0.9% NaCl) given by subcutaneous injection
Sponsors
Alnylam Pharmaceuticals
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
Part A SAD: Inclusion Criteria: * Male or female age 18 - 55 * BMI 18 - 32 kg/m\^2
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 intolerance to SC injection Parts B/C MAD: Inclusion Criteria: * Male or female age 18 - 65 * BMI 18 - 32 kg/m\^2 * Chronic HBV infection for \>/= 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) | Up to 364 days | Number of Subjects with Adverse Events as assessed by CTCAE v5.0. In our planned analysis for this outcome measure, incidence is defined as the number of participants with treatment emergent AEs (TEAEs) in relation to the total number of participants in the cohort. |
| Clinical Assessments Including But Not Limited to Laboratory Test Results | Up to 336 days | Number of participants with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5 | VIR-2218 and metabolite Area under the curve from time 0 to last measurable Time |
| Apparent Terminal Elimination Half-life (h) | Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1 | VIR-2218 Apparent Elimination Half-life t1/2 in Plasma: Median (Inter-Quartile Range Q1-Q3) |
| Apparent Plasma Clearance (L/h) | Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1 | VIR-2218 CL/F Apparent plasma clearance |
| Apparent Volume of Distribution (L) | Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1 | VIR-2218 VZ/F apparent volume of distribution |
| Urine %fe 0-24h | Pooled urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs) | VIR-2218 and metabolite: Fraction excreted in the urine from time 0 to 24 h. Pooled Urine PK samples was collected at pre-specified intervals in the single ascending dose study of VIR-2218. Therefore, the following PK parameter, fraction excreted in the urine ( %fe 0-24h ) was only calculated in healthy subjects who participated in Part A of the study. This parameter was not listed as a secondary endpoint for parts B/C in the submitted protocol, and as such was not reported in this secondary outcome measures. |
| Maximum Plasma Concentration (ng/mL) | Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5 | VIR-2218 and metabolite Maximum Concentration in Plasma |
| Maximum Reduction of Serum HBsAg From Baseline | Up to 112 days | Maximum reduction of serum HBsAg from Day 1 until Week 16. |
| Number of Subjects With Serum HBsAg Loss at Any Time Point | Up to 336 days | Serum HBsAg loss is defined as quantitative HBsAg \< 0.05 IU/mL at two or more consecutive measurements |
| Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months | Up to 336 days | Serum HBsAg loss is defined as quantitative HBsAg \< 0.05 IU/mL at two or more consecutive measurements |
| Number of Subjects With Anti-HBs Seroconversion at Any Timepoint | Up to 336 days | Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements |
| Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | Up to 336 days | HBeAg loss is defined as quantitative HBeAg \< 0.11 IU/mL at two or more consecutive measurements. anti-HBe seroconversion is defined as anti-HBe positivity at two or more consecutive measurements |
| Apparent Renal Clearance (CLR/F) | Pooled Urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs) | VIR-2218 Apparent renal clearance from 0 to 24 h. Pooled Urine PK samples was collected at pre-specified intervals in the single ascending dose study of VIR-2218. Therefore, the following PK parameter, apparent renal clearance (CLR/F) was only calculated in healthy subjects who participated in Part A of the study. This parameter was not listed as a secondary endpoint for parts B/C in the submitted protocol, and as such was not reported in this secondary outcome measures. |
| Time to Reach Maximum Plasma Concentration (h) | Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5 | VIR-2218 and metabolite time of Cmax in Plasma: Median (Inter-Quartile Range Q1-Q3) |
Countries
Australia, Hong Kong, New Zealand, South Korea, Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A: SAD VIR-2218 50 mg Healthy subjects received a single dose of VIR-2218 of 50 mg administered SC
VIR-2218: VIR-2218 given by subcutaneous injection | 6 |
| Part A: SAD VIR-2218 100 mg Healthy subjects received a single dose of VIR-2218 of 100 mg administered SC
VIR-2218: VIR-2218 given by subcutaneous injection | 6 |
| Part A: SAD VIR-2218 200 mg Healthy subjects received a single dose of VIR-2218 of 200 mg administered SC
VIR-2218: VIR-2218 given by subcutaneous injection | 6 |
| Part A: SAD VIR-2218 400 mg Healthy subjects received a single dose of VIR-2218 of 400 mg administered SC
VIR-2218: VIR-2218 given by subcutaneous injection | 7 |
| Part A: SAD VIR-2218 600 mg Healthy subjects received a single dose of VIR-2218 of 600 mg administered SC
VIR-2218: VIR-2218 given by subcutaneous injection | 6 |
| Part A: SAD VIR-2218 900 mg Healthy subjects received a single dose of VIR-2218 of 900 mg administered SC
VIR-2218: VIR-2218 given by subcutaneous injection | 6 |
| Part A: SAD Placebo Healthy subjects received a single dose of placebo administered SC
Placebo: Sterile normal saline (0.9% NaCl) given by subcutaneous injection | 12 |
| Part B: MAD VIR-2218 20 mg Chronic HBV, HBeAg negative, subjects received 2 SC doses of 20 mg VIR-2218 administered 4 weeks apart.
VIR-2218: VIR-2218 given by subcutaneous injection | 3 |
| Part B: MAD VIR-2218 50 mg Chronic HBV, HBeAg negative, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
VIR-2218: VIR-2218 given by subcutaneous injection | 6 |
| Part B: MAD VIR-2218 100 mg Chronic HBV, HBeAg negative, subjects received 2 SC doses of 100 mg VIR-2218 administered 4 weeks apart.
VIR-2218: VIR-2218 given by subcutaneous injection | 6 |
| Part B: MAD VIR-2218 200 mg Chronic HBV, HBeAg negative, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
VIR-2218: VIR-2218 given by subcutaneous injection | 3 |
| Part C: MAD VIR-2218 50 mg Chronic HBV, HBeAg positive, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
VIR-2218: VIR-2218 given by subcutaneous injection | 3 |
| Part C: MAD VIR-2218 200 mg Chronic HBV, HBeAg positive, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
VIR-2218: VIR-2218 given by subcutaneous injection | 3 |
| Part B: MAD Placebo Chronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart.
Placebo: Sterile normal saline (0.9% NaCl) given by subcutaneous injection | 6 |
| Part C: MAD Placebo Chronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.
Placebo: Sterile normal saline (0.9% NaCl) given by subcutaneous injection | 2 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A: SAD VIR-2218 50 mg | Part A: SAD VIR-2218 100 mg | Part B: MAD VIR-2218 50 mg | Part B: MAD VIR-2218 20 mg | Part A: SAD Placebo | Part A: SAD VIR-2218 900 mg | Part A: SAD VIR-2218 600 mg | Part A: SAD VIR-2218 400 mg | Part A: SAD VIR-2218 200 mg | Part B: MAD VIR-2218 100 mg | Part B: MAD VIR-2218 200 mg | Part C: MAD VIR-2218 50 mg | Part C: MAD VIR-2218 200 mg | Part B: MAD Placebo | Part C: MAD Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 25 Years STANDARD_DEVIATION 3 | 23.3 Years STANDARD_DEVIATION 4 | 42.5 Years STANDARD_DEVIATION 10.8 | 40.3 Years STANDARD_DEVIATION 9.1 | 26.5 Years STANDARD_DEVIATION 6.7 | 32.5 Years STANDARD_DEVIATION 9.5 | 28.8 Years STANDARD_DEVIATION 6.3 | 24.3 Years STANDARD_DEVIATION 3.7 | 26.7 Years STANDARD_DEVIATION 3.8 | 45.2 Years STANDARD_DEVIATION 5.5 | 55 Years STANDARD_DEVIATION 4 | 35 Years STANDARD_DEVIATION 9.8 | 33.7 Years STANDARD_DEVIATION 13.1 | 44 Years STANDARD_DEVIATION 7.2 | 58.5 Years STANDARD_DEVIATION 7.8 | 33.4 Years STANDARD_DEVIATION 11.5 |
| Alanine Aminotransferase Levels | — | — | 23.5 U/L STANDARD_DEVIATION 14.9 | 15.3 U/L STANDARD_DEVIATION 4.6 | — | — | — | — | — | 14.3 U/L STANDARD_DEVIATION 5 | 10.0 U/L STANDARD_DEVIATION 4 | 27.7 U/L STANDARD_DEVIATION 18.6 | 26.0 U/L STANDARD_DEVIATION 17.7 | 21.8 U/L STANDARD_DEVIATION 17.6 | 26.5 U/L STANDARD_DEVIATION 10.6 | 20.25 U/L STANDARD_DEVIATION 13.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 11 Participants | 5 Participants | 6 Participants | 7 Participants | 6 Participants | 6 Participants | 3 Participants | 3 Participants | 3 Participants | 6 Participants | 2 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Hepatitis B Surface Antigen Levels (IU/mL) | — | — | 3872.625 IU/mL STANDARD_DEVIATION 5678.292 | 2372.227 IU/mL STANDARD_DEVIATION 1168.94 | — | — | — | — | — | 4009.863 IU/mL STANDARD_DEVIATION 5239.703 | 2374.423 IU/mL STANDARD_DEVIATION 2078.034 | 3488.037 IU/mL STANDARD_DEVIATION 2454.215 | 12640.983 IU/mL STANDARD_DEVIATION 10495.983 | 4819.127 IU/mL STANDARD_DEVIATION 6348.594 | 1886.045 IU/mL STANDARD_DEVIATION 1223.655 | 4456.52 IU/mL STANDARD_DEVIATION 5657.74 |
| 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 |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 5 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 6 Participants | 2 Participants | 39 Participants |
| Race (NIH/OMB) Black or African American | 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) 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 |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 8 Participants | 3 Participants | 3 Participants | 5 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 29 Participants |
| Region of Enrollment Australia | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants | 0 participants | 0 participants | 2 participants | 0 participants | 0 participants | 4 participants |
| Region of Enrollment Hong Kong | 0 participants | 0 participants | 3 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 2 participants | 0 participants | 8 participants |
| Region of Enrollment New Zealand | 6 participants | 6 participants | 2 participants | 0 participants | 12 participants | 6 participants | 6 participants | 7 participants | 6 participants | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 54 participants |
| Region of Enrollment South Korea | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants | 2 participants | 1 participants | 0 participants | 1 participants | 0 participants | 8 participants |
| Region of Enrollment Thailand | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 3 participants | 1 participants | 7 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 1 Participants | 1 Participants | 5 Participants | 3 Participants | 3 Participants | 7 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 44 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 5 Participants | 2 Participants | 7 Participants | 3 Participants | 3 Participants | 0 Participants | 3 Participants | 5 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 37 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 | 1 / 3 | 0 / 6 | 0 / 2 |
| other Total, other adverse events | 4 / 6 | 3 / 6 | 4 / 6 | 5 / 7 | 3 / 6 | 3 / 6 | 6 / 12 | 0 / 3 | 2 / 6 | 5 / 6 | 2 / 3 | 2 / 3 | 2 / 3 | 1 / 6 | 1 / 2 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 3 | 0 / 6 | 1 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 2 |
Outcome results
Primary
Clinical Assessments Including But Not Limited to Laboratory Test Results
Number of participants with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.
Time frame: Up to 336 days
Population: Number of participants analyzed is inclusive of clinically significant Vital Signs, ECGs, and Lab Findings. The Overall Number of Participants Analyzed is not consistent with numbers provided in the rows of the Participant Flow module. This inconsistency has been explained in the Analysis Population Description in our First Primary Outcome Measure as well.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: SAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 1 Participants |
| Part A: SAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 3 Participants |
| Part A: SAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part A: SAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 1 Participants |
| Part A: SAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 1 Participants |
| Part A: SAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part A: SAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part A: SAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 2 Participants |
| Part A: SAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part A: SAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 1 Participants |
| Part A: SAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part A: SAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part A: SAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 3 Participants |
| Part A: SAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part A: SAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 1 Participants |
| Part A: SAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part A: SAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part A: SAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 3 Participants |
| Part A: SAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part A: SAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part A: SAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 1 Participants |
| Part A: SAD VIR-2218 400 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part A: SAD VIR-2218 400 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part A: SAD VIR-2218 400 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 4 Participants |
| Part A: SAD VIR-2218 400 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part A: SAD VIR-2218 400 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 1 Participants |
| Part A: SAD VIR-2218 400 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 1 Participants |
| Part A: SAD VIR-2218 400 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 1 Participants |
| Part A: SAD VIR-2218 600 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part A: SAD VIR-2218 600 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 4 Participants |
| Part A: SAD VIR-2218 600 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 1 Participants |
| Part A: SAD VIR-2218 600 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part A: SAD VIR-2218 600 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 1 Participants |
| Part A: SAD VIR-2218 600 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part A: SAD VIR-2218 600 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part A: SAD VIR-2219 900 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 3 Participants |
| Part A: SAD VIR-2219 900 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 3 Participants |
| Part A: SAD VIR-2219 900 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 0 Participants |
| Part A: SAD VIR-2219 900 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part A: SAD VIR-2219 900 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part A: SAD VIR-2219 900 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part A: SAD VIR-2219 900 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part A: SAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part A: SAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 1 Participants |
| Part A: SAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 3 Participants |
| Part A: SAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part A: SAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part A: SAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 1 Participants |
| Part A: SAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 7 Participants |
| Part B: MAD VIR-2218 20 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part B: MAD VIR-2218 20 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 1 Participants |
| Part B: MAD VIR-2218 20 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 2 Participants |
| Part B: MAD VIR-2218 20 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 0 Participants |
| Part B: MAD VIR-2218 20 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part B: MAD VIR-2218 20 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part B: MAD VIR-2218 20 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part B: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part B: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part B: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part B: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 2 Participants |
| Part B: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 0 Participants |
| Part B: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part B: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 4 Participants |
| Part B: MAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 1 Participants |
| Part B: MAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part B: MAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part B: MAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 5 Participants |
| Part B: MAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part B: MAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part B: MAD VIR-2218 100 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 0 Participants |
| Part B: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part B: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 0 Participants |
| Part B: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 0 Participants |
| Part B: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part B: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part B: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 3 Participants |
| Part B: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part C: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part C: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 0 Participants |
| Part C: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part C: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 3 Participants |
| Part C: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part C: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 0 Participants |
| Part C: MAD VIR-2218 50 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part C: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part C: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 0 Participants |
| Part C: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part C: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 3 Participants |
| Part C: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part C: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 0 Participants |
| Part C: MAD VIR-2218 200 mg | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part B: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 3 Participants |
| Part B: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part B: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 1 Participants |
| Part B: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part B: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part B: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 2 Participants |
| Part B: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
| Part C: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant Vital Signs | 0 Participants |
| Part C: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 1 | 2 Participants |
| Part C: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 2 | 0 Participants |
| Part C: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 3 | 0 Participants |
| Part C: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 4 | 0 Participants |
| Part C: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | CTCAE v5.0 Lab Grade 0 | 0 Participants |
| Part C: MAD Placebo | Clinical Assessments Including But Not Limited to Laboratory Test Results | Clinically Significant ECG | 0 Participants |
Primary
Incidence of Adverse Events (AEs)
Number of Subjects with Adverse Events as assessed by CTCAE v5.0. In our planned analysis for this outcome measure, incidence is defined as the number of participants with treatment emergent AEs (TEAEs) in relation to the total number of participants in the cohort.
Time frame: Up to 364 days
Population: The Overall Number of Participants Analyzed is not consistent with numbers provided in the rows of the Participant Flow module because we enrolled and randomized 8 participants for the Part A 400 mg cohort, but only 7 of these participants were dosed and included for full analysis dataset. We have added a row for dosed participants in the Participant Flow module, to clarify this inconsistency and reflect the number of participants in the analysis dataset.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: SAD VIR-2218 50 mg | Incidence of Adverse Events (AEs) | 4 Participants |
| Part A: SAD VIR-2218 100 mg | Incidence of Adverse Events (AEs) | 3 Participants |
| Part A: SAD VIR-2218 200 mg | Incidence of Adverse Events (AEs) | 4 Participants |
| Part A: SAD VIR-2218 400 mg | Incidence of Adverse Events (AEs) | 5 Participants |
| Part A: SAD VIR-2218 600 mg | Incidence of Adverse Events (AEs) | 3 Participants |
| Part A: SAD VIR-2219 900 mg | Incidence of Adverse Events (AEs) | 3 Participants |
| Part A: SAD Placebo | Incidence of Adverse Events (AEs) | 6 Participants |
| Part B: MAD VIR-2218 20 mg | Incidence of Adverse Events (AEs) | 0 Participants |
| Part B: MAD VIR-2218 50 mg | Incidence of Adverse Events (AEs) | 2 Participants |
| Part B: MAD VIR-2218 100 mg | Incidence of Adverse Events (AEs) | 5 Participants |
| Part B: MAD VIR-2218 200 mg | Incidence of Adverse Events (AEs) | 2 Participants |
| Part C: MAD VIR-2218 50 mg | Incidence of Adverse Events (AEs) | 2 Participants |
| Part C: MAD VIR-2218 200 mg | Incidence of Adverse Events (AEs) | 2 Participants |
| Part B: MAD Placebo | Incidence of Adverse Events (AEs) | 1 Participants |
| Part C: MAD Placebo | Incidence of Adverse Events (AEs) | 1 Participants |
Secondary
Apparent Plasma Clearance (L/h)
VIR-2218 CL/F Apparent plasma clearance
Time frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1
Population: The PK Analysis Set includes all randomized subjects who had at least 1 dose of VIR-2218 and 1 post-baseline PK parameter
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: SAD VIR-2218 50 mg | Apparent Plasma Clearance (L/h) | 34.0 L/h | Standard Deviation 2.54 |
| Part A: SAD VIR-2218 100 mg | Apparent Plasma Clearance (L/h) | 21.8 L/h | Standard Deviation 4.27 |
| Part A: SAD VIR-2218 200 mg | Apparent Plasma Clearance (L/h) | 30.8 L/h | Standard Deviation 4.51 |
| Part A: SAD VIR-2218 400 mg | Apparent Plasma Clearance (L/h) | 16.8 L/h | Standard Deviation 1.76 |
| Part A: SAD VIR-2218 600 mg | Apparent Plasma Clearance (L/h) | 21.9 L/h | Standard Deviation 6.91 |
| Part A: SAD VIR-2219 900 mg | Apparent Plasma Clearance (L/h) | 15.3 L/h | Standard Deviation 2.08 |
Secondary
Apparent Renal Clearance (CLR/F)
VIR-2218 Apparent renal clearance from 0 to 24 h. Pooled Urine PK samples was collected at pre-specified intervals in the single ascending dose study of VIR-2218. Therefore, the following PK parameter, apparent renal clearance (CLR/F) was only calculated in healthy subjects who participated in Part A of the study. This parameter was not listed as a secondary endpoint for parts B/C in the submitted protocol, and as such was not reported in this secondary outcome measures.
Time frame: Pooled Urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)
Population: The PK Analysis Set includes all randomized subjects who had at least 1 dose of VIR-2218 and 1 post-baseline PK parameter
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: SAD VIR-2218 50 mg | Apparent Renal Clearance (CLR/F) | 5.87 L/h | Standard Deviation 0.728 |
| Part A: SAD VIR-2218 100 mg | Apparent Renal Clearance (CLR/F) | 5.22 L/h | Standard Deviation 1.27 |
| Part A: SAD VIR-2218 200 mg | Apparent Renal Clearance (CLR/F) | 7.00 L/h | Standard Deviation 0.659 |
| Part A: SAD VIR-2218 400 mg | Apparent Renal Clearance (CLR/F) | 5.13 L/h | Standard Deviation 0.85 |
| Part A: SAD VIR-2218 600 mg | Apparent Renal Clearance (CLR/F) | 7.22 L/h | Standard Deviation 1.48 |
| Part A: SAD VIR-2219 900 mg | Apparent Renal Clearance (CLR/F) | 7.47 L/h | Standard Deviation 1.34 |
Secondary
Apparent Terminal Elimination Half-life (h)
VIR-2218 Apparent Elimination Half-life t1/2 in Plasma: Median (Inter-Quartile Range Q1-Q3)
Time frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1
Population: The PK Analysis Set includes all randomized subjects who had at least 1 dose of VIR-2218 and 1 post-baseline PK parameter
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: SAD VIR-2218 50 mg | Apparent Terminal Elimination Half-life (h) | 2.45 h |
| Part A: SAD VIR-2218 100 mg | Apparent Terminal Elimination Half-life (h) | 3.64 h |
| Part A: SAD VIR-2218 200 mg | Apparent Terminal Elimination Half-life (h) | 4.38 h |
| Part A: SAD VIR-2218 400 mg | Apparent Terminal Elimination Half-life (h) | 3.54 h |
| Part A: SAD VIR-2218 600 mg | Apparent Terminal Elimination Half-life (h) | 5.28 h |
| Part A: SAD VIR-2219 900 mg | Apparent Terminal Elimination Half-life (h) | 4.55 h |
Secondary
Apparent Volume of Distribution (L)
VIR-2218 VZ/F apparent volume of distribution
Time frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1
Population: The PK Analysis Set includes all randomized subjects who had at least 1 dose of VIR-2218 and 1 post-baseline PK parameter
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: SAD VIR-2218 50 mg | Apparent Volume of Distribution (L) | 155 L | Standard Deviation 69.7 |
| Part A: SAD VIR-2218 100 mg | Apparent Volume of Distribution (L) | 132 L | Standard Deviation 40.7 |
| Part A: SAD VIR-2218 200 mg | Apparent Volume of Distribution (L) | 223 L | Standard Deviation 76 |
| Part A: SAD VIR-2218 400 mg | Apparent Volume of Distribution (L) | 104 L | Standard Deviation 62.6 |
| Part A: SAD VIR-2218 600 mg | Apparent Volume of Distribution (L) | 176 L | Standard Deviation 60.8 |
| Part A: SAD VIR-2219 900 mg | Apparent Volume of Distribution (L) | 92.9 L | Standard Deviation 24.6 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (ng*h/mL)
VIR-2218 and metabolite Area under the curve from time 0 to last measurable Time
Time frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5
Population: The PK Analysis Set includes all randomized subjects who had at least 1 dose of VIR-2218 and 1 post-baseline PK parameter
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAD VIR-2218 50 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 1) | 1270 h*ng/mL | Standard Deviation 270 |
| Part A: SAD VIR-2218 50 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218 AUClast (Day 1) | NA h*ng/mL | — |
| Part A: SAD VIR-2218 100 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218 AUClast (Day 1) | 208 h*ng/mL | Standard Deviation 190 |
| Part A: SAD VIR-2218 100 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 1) | 3740 h*ng/mL | Standard Deviation 1190 |
| Part A: SAD VIR-2218 200 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218 AUClast (Day 1) | 481 h*ng/mL | Standard Deviation 149 |
| Part A: SAD VIR-2218 200 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 1) | 6630 h*ng/mL | Standard Deviation 1160 |
| Part A: SAD VIR-2218 400 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218 AUClast (Day 1) | 2530 h*ng/mL | Standard Deviation 613 |
| Part A: SAD VIR-2218 400 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 1) | 23500 h*ng/mL | Standard Deviation 2700 |
| Part A: SAD VIR-2218 600 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218 AUClast (Day 1) | 2680 h*ng/mL | Standard Deviation 1460 |
| Part A: SAD VIR-2218 600 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 1) | 27900 h*ng/mL | Standard Deviation 7540 |
| Part A: SAD VIR-2219 900 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 1) | 58800 h*ng/mL | Standard Deviation 9070 |
| Part A: SAD VIR-2219 900 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218 AUClast (Day 1) | 6430 h*ng/mL | Standard Deviation 1500 |
| Part A: SAD Placebo | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218 AUClast (Day 1) | NA h*ng/mL | — |
| Part A: SAD Placebo | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218AUClast (Day 29) | NA h*ng/mL | — |
| Part A: SAD Placebo | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 29) | 339 h*ng/mL | Standard Deviation 171 |
| Part A: SAD Placebo | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 1) | 360 h*ng/mL | Standard Deviation 199 |
| Part B: MAD VIR-2218 20 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 1) | 1000 h*ng/mL | Standard Deviation 285 |
| Part B: MAD VIR-2218 20 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218AUClast (Day 29) | NA h*ng/mL | — |
| Part B: MAD VIR-2218 20 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218 AUClast (Day 1) | NA h*ng/mL | — |
| Part B: MAD VIR-2218 20 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 29) | 910 h*ng/mL | Standard Deviation 326 |
| Part B: MAD VIR-2218 50 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218 AUClast (Day 1) | NA h*ng/mL | — |
| Part B: MAD VIR-2218 50 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218AUClast (Day 29) | 174 h*ng/mL | — |
| Part B: MAD VIR-2218 50 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 29) | 2550 h*ng/mL | Standard Deviation 638 |
| Part B: MAD VIR-2218 50 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 1) | 2700 h*ng/mL | Standard Deviation 943 |
| Part B: MAD VIR-2218 100 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218AUClast (Day 29) | 393 h*ng/mL | Standard Deviation 230 |
| Part B: MAD VIR-2218 100 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | AS(N-1) 3' VIR-2218 AUClast (Day 1) | 482 h*ng/mL | Standard Deviation 199 |
| Part B: MAD VIR-2218 100 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 29) | 9580 h*ng/mL | Standard Deviation 3240 |
| Part B: MAD VIR-2218 100 mg | Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) | VIR-2218 AUClast (Day 1) | 9570 h*ng/mL | Standard Deviation 2410 |
Secondary
Maximum Plasma Concentration (ng/mL)
VIR-2218 and metabolite Maximum Concentration in Plasma
Time frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5
Population: The PK Analysis Set includes all randomized subjects who had at least 1 dose of VIR-2218 and 1 post-baseline PK parameter
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAD VIR-2218 50 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 1) | NA ng/mL | — |
| Part A: SAD VIR-2218 50 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 1) | 155 ng/mL | Standard Deviation 65.3 |
| Part A: SAD VIR-2218 100 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 1) | 40.5 ng/mL | — |
| Part A: SAD VIR-2218 100 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 1) | 355 ng/mL | Standard Deviation 117 |
| Part A: SAD VIR-2218 200 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 1) | 62.4 ng/mL | Standard Deviation 17.6 |
| Part A: SAD VIR-2218 200 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 1) | 711 ng/mL | Standard Deviation 207 |
| Part A: SAD VIR-2218 400 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 1) | 2110 ng/mL | Standard Deviation 722 |
| Part A: SAD VIR-2218 400 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 1) | 259 ng/mL | Standard Deviation 114 |
| Part A: SAD VIR-2218 600 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 1) | 177 ng/mL | Standard Deviation 99.2 |
| Part A: SAD VIR-2218 600 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 1) | 1830 ng/mL | Standard Deviation 615 |
| Part A: SAD VIR-2219 900 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 1) | 5010 ng/mL | Standard Deviation 630 |
| Part A: SAD VIR-2219 900 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 1) | 514 ng/mL | Standard Deviation 106 |
| Part A: SAD Placebo | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 29) | 51.8 ng/mL | Standard Deviation 21.1 |
| Part A: SAD Placebo | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 29) | NA ng/mL | — |
| Part A: SAD Placebo | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 1) | 73.5 ng/mL | — |
| Part A: SAD Placebo | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 1) | NA ng/mL | — |
| Part B: MAD VIR-2218 20 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 29) | 115 ng/mL | Standard Deviation 38.2 |
| Part B: MAD VIR-2218 20 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 1) | 118 ng/mL | Standard Deviation 61.2 |
| Part B: MAD VIR-2218 20 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 1) | NA ng/mL | — |
| Part B: MAD VIR-2218 20 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 29) | NA ng/mL | — |
| Part B: MAD VIR-2218 50 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 1) | NA ng/mL | — |
| Part B: MAD VIR-2218 50 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 29) | 256 ng/mL | Standard Deviation 167 |
| Part B: MAD VIR-2218 50 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 1) | 235 ng/mL | Standard Deviation 79 |
| Part B: MAD VIR-2218 50 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 29) | NA ng/mL | — |
| Part B: MAD VIR-2218 100 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 1) | 66.1 ng/mL | — |
| Part B: MAD VIR-2218 100 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 1) | 826 ng/mL | Standard Deviation 336 |
| Part B: MAD VIR-2218 100 mg | Maximum Plasma Concentration (ng/mL) | AS (N-1)3' VIR-2218 Cmax (Day 29) | 75.1 ng/mL | Standard Deviation 27.2 |
| Part B: MAD VIR-2218 100 mg | Maximum Plasma Concentration (ng/mL) | VIR-2218 Cmax (Day 29) | 807 ng/mL | Standard Deviation 374 |
Secondary
Maximum Reduction of Serum HBsAg From Baseline
Maximum reduction of serum HBsAg from Day 1 until Week 16.
Time frame: Up to 112 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: SAD VIR-2218 50 mg | Maximum Reduction of Serum HBsAg From Baseline | -1.031 log10 IU/mL | Standard Deviation 0.574 |
| Part A: SAD VIR-2218 100 mg | Maximum Reduction of Serum HBsAg From Baseline | -1.230 log10 IU/mL | Standard Deviation 0.702 |
| Part A: SAD VIR-2218 200 mg | Maximum Reduction of Serum HBsAg From Baseline | -1.504 log10 IU/mL | Standard Deviation 0.54 |
| Part A: SAD VIR-2218 400 mg | Maximum Reduction of Serum HBsAg From Baseline | -1.653 log10 IU/mL | Standard Deviation 0.154 |
| Part A: SAD VIR-2218 600 mg | Maximum Reduction of Serum HBsAg From Baseline | -1.161 log10 IU/mL | Standard Deviation 0.35 |
| Part A: SAD VIR-2219 900 mg | Maximum Reduction of Serum HBsAg From Baseline | -1.568 log10 IU/mL | Standard Deviation 0.636 |
| Part A: SAD Placebo | Maximum Reduction of Serum HBsAg From Baseline | -0.098 log10 IU/mL | Standard Deviation 0.047 |
| Part B: MAD VIR-2218 20 mg | Maximum Reduction of Serum HBsAg From Baseline | -0.068 log10 IU/mL | Standard Deviation 0.01 |
Secondary
Number of Subjects 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 336 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: SAD VIR-2218 50 mg | Number of Subjects With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part A: SAD VIR-2218 100 mg | Number of Subjects With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part A: SAD VIR-2218 200 mg | Number of Subjects With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part A: SAD VIR-2218 400 mg | Number of Subjects With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part A: SAD VIR-2218 600 mg | Number of Subjects With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part A: SAD VIR-2219 900 mg | Number of Subjects With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part A: SAD Placebo | Number of Subjects With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
| Part B: MAD VIR-2218 20 mg | Number of Subjects With Anti-HBs Seroconversion at Any Timepoint | 0 Participants |
Secondary
Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint
HBeAg loss is defined as quantitative HBeAg \< 0.11 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 336 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: SAD VIR-2218 50 mg | Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | Number of Subjects with HBeAg Loss | 0 Participants |
| Part A: SAD VIR-2218 50 mg | Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | Number of Subjects with anti-HBe seroconversion | 0 Participants |
| Part A: SAD VIR-2218 100 mg | Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | Number of Subjects with HBeAg Loss | 1 Participants |
| Part A: SAD VIR-2218 100 mg | Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | Number of Subjects with anti-HBe seroconversion | 1 Participants |
| Part A: SAD VIR-2218 200 mg | Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | Number of Subjects with HBeAg Loss | 0 Participants |
| Part A: SAD VIR-2218 200 mg | Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint | Number of Subjects with anti-HBe seroconversion | 0 Participants |
Secondary
Number of Subjects With Serum HBsAg Loss at Any Time Point
Serum HBsAg loss is defined as quantitative HBsAg \< 0.05 IU/mL at two or more consecutive measurements
Time frame: Up to 336 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: SAD VIR-2218 50 mg | Number of Subjects With Serum HBsAg Loss at Any Time Point | 0 Participants |
| Part A: SAD VIR-2218 100 mg | Number of Subjects With Serum HBsAg Loss at Any Time Point | 0 Participants |
| Part A: SAD VIR-2218 200 mg | Number of Subjects With Serum HBsAg Loss at Any Time Point | 0 Participants |
| Part A: SAD VIR-2218 400 mg | Number of Subjects With Serum HBsAg Loss at Any Time Point | 0 Participants |
| Part A: SAD VIR-2218 600 mg | Number of Subjects With Serum HBsAg Loss at Any Time Point | 0 Participants |
| Part A: SAD VIR-2219 900 mg | Number of Subjects With Serum HBsAg Loss at Any Time Point | 0 Participants |
| Part A: SAD Placebo | Number of Subjects With Serum HBsAg Loss at Any Time Point | 0 Participants |
| Part B: MAD VIR-2218 20 mg | Number of Subjects With Serum HBsAg Loss at Any Time Point | 0 Participants |
Secondary
Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months
Serum HBsAg loss is defined as quantitative HBsAg \< 0.05 IU/mL at two or more consecutive measurements
Time frame: Up to 336 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: SAD VIR-2218 50 mg | Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months | 0 Participants |
| Part A: SAD VIR-2218 100 mg | Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months | 0 Participants |
| Part A: SAD VIR-2218 200 mg | Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months | 0 Participants |
| Part A: SAD VIR-2218 400 mg | Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months | 0 Participants |
| Part A: SAD VIR-2218 600 mg | Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months | 0 Participants |
| Part A: SAD VIR-2219 900 mg | Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months | 0 Participants |
| Part A: SAD Placebo | Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months | 0 Participants |
| Part B: MAD VIR-2218 20 mg | Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months | 0 Participants |
Secondary
Time to Reach Maximum Plasma Concentration (h)
VIR-2218 and metabolite time of Cmax in Plasma: Median (Inter-Quartile Range Q1-Q3)
Time frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5
Population: The PK Analysis Set includes all randomized subjects who had at least 1 dose of VIR-2218 and 1 post-baseline PK parameter
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: SAD VIR-2218 50 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 1 | 4.25 h |
| Part A: SAD VIR-2218 50 mg | Time to Reach Maximum Plasma Concentration (h) | AS(N-1)3' VIR-2218 Tmax Day 1 | NA h |
| Part A: SAD VIR-2218 100 mg | Time to Reach Maximum Plasma Concentration (h) | AS(N-1)3' VIR-2218 Tmax Day 1 | 6.17 h |
| Part A: SAD VIR-2218 100 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 1 | 4.32 h |
| Part A: SAD VIR-2218 200 mg | Time to Reach Maximum Plasma Concentration (h) | AS(N-1)3' VIR-2218 Tmax Day 1 | 6.17 h |
| Part A: SAD VIR-2218 200 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 1 | 5.21 h |
| Part A: SAD VIR-2218 400 mg | Time to Reach Maximum Plasma Concentration (h) | AS(N-1)3' VIR-2218 Tmax Day 1 | 9.21 h |
| Part A: SAD VIR-2218 400 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 1 | 7.21 h |
| Part A: SAD VIR-2218 600 mg | Time to Reach Maximum Plasma Concentration (h) | AS(N-1)3' VIR-2218 Tmax Day 1 | 10.2 h |
| Part A: SAD VIR-2218 600 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 1 | 7.21 h |
| Part A: SAD VIR-2219 900 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 1 | 4.25 h |
| Part A: SAD VIR-2219 900 mg | Time to Reach Maximum Plasma Concentration (h) | AS(N-1)3' VIR-2218 Tmax Day 1 | 8.25 h |
| Part A: SAD Placebo | Time to Reach Maximum Plasma Concentration (h) | AS(N-1)3' VIR-2218 Tmax Day 1 | NA h |
| Part A: SAD Placebo | Time to Reach Maximum Plasma Concentration (h) | AS (N-1)3' VIR-2218 Tmax Day 29 | NA h |
| Part A: SAD Placebo | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 29 | 3.95 h |
| Part A: SAD Placebo | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 1 | 4.00 h |
| Part B: MAD VIR-2218 20 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 1 | 7.63 h |
| Part B: MAD VIR-2218 20 mg | Time to Reach Maximum Plasma Concentration (h) | AS (N-1)3' VIR-2218 Tmax Day 29 | NA h |
| Part B: MAD VIR-2218 20 mg | Time to Reach Maximum Plasma Concentration (h) | AS(N-1)3' VIR-2218 Tmax Day 1 | NA h |
| Part B: MAD VIR-2218 20 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 29 | 4.00 h |
| Part B: MAD VIR-2218 50 mg | Time to Reach Maximum Plasma Concentration (h) | AS(N-1)3' VIR-2218 Tmax Day 1 | NA h |
| Part B: MAD VIR-2218 50 mg | Time to Reach Maximum Plasma Concentration (h) | AS (N-1)3' VIR-2218 Tmax Day 29 | 6.00 h |
| Part B: MAD VIR-2218 50 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 29 | 8.00 h |
| Part B: MAD VIR-2218 50 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 1 | 2.48 h |
| Part B: MAD VIR-2218 100 mg | Time to Reach Maximum Plasma Concentration (h) | AS (N-1)3' VIR-2218 Tmax Day 29 | 5.99 h |
| Part B: MAD VIR-2218 100 mg | Time to Reach Maximum Plasma Concentration (h) | AS(N-1)3' VIR-2218 Tmax Day 1 | 8.00 h |
| Part B: MAD VIR-2218 100 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 29 | 3.99 h |
| Part B: MAD VIR-2218 100 mg | Time to Reach Maximum Plasma Concentration (h) | VIR-2218 Tmax Day 1 | 5.98 h |
Secondary
Urine %fe 0-24h
VIR-2218 and metabolite: Fraction excreted in the urine from time 0 to 24 h. Pooled Urine PK samples was collected at pre-specified intervals in the single ascending dose study of VIR-2218. Therefore, the following PK parameter, fraction excreted in the urine ( %fe 0-24h ) was only calculated in healthy subjects who participated in Part A of the study. This parameter was not listed as a secondary endpoint for parts B/C in the submitted protocol, and as such was not reported in this secondary outcome measures.
Time frame: Pooled urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)
Population: The PK Analysis Set includes all randomized subjects who had at least 1 dose of VIR-2218 and 1 post-baseline PK parameter
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAD VIR-2218 50 mg | Urine %fe 0-24h | VIR-2218 fe 0-24 | 16.9 % excreted in the urine from time 0-24h | Standard Deviation 3.19 |
| Part A: SAD VIR-2218 50 mg | Urine %fe 0-24h | AS(N-1)3' VIR-2218 fe 0-24 | 1.94 % excreted in the urine from time 0-24h | Standard Deviation 0.48 |
| Part A: SAD VIR-2218 100 mg | Urine %fe 0-24h | AS(N-1)3' VIR-2218 fe 0-24 | 4.16 % excreted in the urine from time 0-24h | Standard Deviation 2.28 |
| Part A: SAD VIR-2218 100 mg | Urine %fe 0-24h | VIR-2218 fe 0-24 | 21.7 % excreted in the urine from time 0-24h | Standard Deviation 6.22 |
| Part A: SAD VIR-2218 200 mg | Urine %fe 0-24h | AS(N-1)3' VIR-2218 fe 0-24 | 3.31 % excreted in the urine from time 0-24h | Standard Deviation 0.656 |
| Part A: SAD VIR-2218 200 mg | Urine %fe 0-24h | VIR-2218 fe 0-24 | 23.2 % excreted in the urine from time 0-24h | Standard Deviation 4.34 |
| Part A: SAD VIR-2218 400 mg | Urine %fe 0-24h | VIR-2218 fe 0-24 | 29.5 % excreted in the urine from time 0-24h | Standard Deviation 5.72 |
| Part A: SAD VIR-2218 400 mg | Urine %fe 0-24h | AS(N-1)3' VIR-2218 fe 0-24 | 4.99 % excreted in the urine from time 0-24h | Standard Deviation 0.74 |
| Part A: SAD VIR-2218 600 mg | Urine %fe 0-24h | VIR-2218 fe 0-24 | 32.3 % excreted in the urine from time 0-24h | Standard Deviation 11.7 |
| Part A: SAD VIR-2218 600 mg | Urine %fe 0-24h | AS(N-1)3' VIR-2218 fe 0-24 | 4.12 % excreted in the urine from time 0-24h | Standard Deviation 2.31 |
| Part A: SAD VIR-2219 900 mg | Urine %fe 0-24h | AS(N-1)3' VIR-2218 fe 0-24 | 6.96 % excreted in the urine from time 0-24h | Standard Deviation 1.47 |
| Part A: SAD VIR-2219 900 mg | Urine %fe 0-24h | VIR-2218 fe 0-24 | 47.6 % excreted in the urine from time 0-24h | Standard Deviation 8.59 |