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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
82
Investigative Site
Birtinya, Queensland, Australia
Investigative Site
Clayton, Victoria, Australia
Investigative Site
Fitzroy, Victoria, Australia
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
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
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
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
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
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Investigative Site
Hong Kong, Hong Kong
Investigative Site
Auckland, New Zealand
Investigative Site
Auckland, New Zealand
Investigative Site
Busan, South Korea
Investigative Site
Seoul, South Korea
Investigative Site
Seoul, South Korea
Investigative Site
Bangkok, Thailand
...and 4 more locations
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
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
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
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)
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)
Maximum Reduction of Serum HBsAg From Baseline
Maximum reduction of serum HBsAg from Day 1 until Week 16.
Time frame: Up to 112 days
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
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
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
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