Title
Study of VIR-2218 in Healthy Subjects and Patients With Chronic Hepatitis B
A Phase 1/2, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-2218
Phase
Phase 1/Phase 2Lead Sponsor
Vir Biotechnology, Inc.Study Type
InterventionalStatus
Completed Results PostedIndication/Condition
Chronic Hepatitis BIntervention/Treatment
VIR-2218 ...Study Participants
82This 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.
VIR-2218 given by subcutaneous injection
Sterile normal saline (0.9% NaCl) given by subcutaneous injection
Healthy subjects received a single dose of VIR-2218 of 50 mg administered SC
Healthy subjects received a single dose of VIR-2218 of 100 mg administered SC
Healthy subjects received a single dose of VIR-2218 of 200 mg administered SC
Healthy subjects received a single dose of VIR-2218 of 400 mg administered SC
Healthy subjects received a single dose of VIR-2218 of 600 mg administered SC
Healthy subjects received a single dose of VIR-2218 of 900 mg administered SC
Healthy subjects received a single dose of placebo administered SC
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 20 mg VIR-2218 administered 4 weeks apart.
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 100 mg VIR-2218 administered 4 weeks apart.
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
Chronic HBV, HBeAg positive, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
Chronic HBV, HBeAg positive, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
Chronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart.
Chronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.
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 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
| Event Type | Organ System | Event Term | Part A SAD: VIR-2218 50 mg | Part A SAD: VIR-2218 100 mg | Part A SAD: VIR-2218 200 mg | Part A SAD: VIR-2218 400 mg | Part A SAD: VIR-2218 600 mg | Part A SAD: VIR-2218 900 mg | Part A SAD: Placebo | Part B MAD: VIR-2218 20 mg | Part B MAD: VIR-2218 50 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 |
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Number of participants with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.
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.
VIR-2218 and metabolite Maximum Concentration in Plasma
VIR-2218 and metabolite time of Cmax in Plasma: Median (Inter-Quartile Range Q1-Q3)
VIR-2218 and metabolite Area under the curve from time 0 to last measurable Time
VIR-2218 Apparent Elimination Half-life t1/2 in Plasma: Median (Inter-Quartile Range Q1-Q3)
VIR-2218 CL/F Apparent plasma clearance
VIR-2218 VZ/F apparent volume of distribution
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.
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.
Maximum reduction of serum HBsAg from Day 1 until Week 16.
Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements
Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements
Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements
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
