Study of VIR-2218 in Healthy Subjects and Patients With Chronic Hepatitis B
- Registration Number
- NCT03672188
- Lead Sponsor
- Vir Biotechnology, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
- Male or female age 18 - 55
- BMI 18 - 32 kg/m^2
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: SAD VIR-2218 100 mg VIR-2218 Healthy subjects received a single dose of VIR-2218 of 100 mg administered SC Part A: SAD VIR-2218 200 mg VIR-2218 Healthy subjects received a single dose of VIR-2218 of 200 mg administered SC Part A: SAD VIR-2218 600 mg VIR-2218 Healthy subjects received a single dose of VIR-2218 of 600 mg administered SC Part B: MAD VIR-2218 20 mg VIR-2218 Chronic HBV, HBeAg negative, subjects received 2 SC doses of 20 mg VIR-2218 administered 4 weeks apart. Part B: MAD VIR-2218 50 mg VIR-2218 Chronic HBV, HBeAg negative, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart. Part B: MAD VIR-2218 200 mg VIR-2218 Chronic HBV, HBeAg negative, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart. Part C: MAD VIR-2218 50 mg VIR-2218 Chronic HBV, HBeAg positive, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart. Part C: MAD VIR-2218 200 mg VIR-2218 Chronic HBV, HBeAg positive, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart. Part A: SAD VIR-2218 400 mg VIR-2218 Healthy subjects received a single dose of VIR-2218 of 400 mg administered SC Part A: SAD VIR-2218 900 mg VIR-2218 Healthy subjects received a single dose of VIR-2218 of 900 mg administered SC Part B: MAD VIR-2218 100 mg VIR-2218 Chronic HBV, HBeAg negative, subjects received 2 SC doses of 100 mg VIR-2218 administered 4 weeks apart. Part B: MAD Placebo Placebo Chronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart. Part A: SAD Placebo Placebo Healthy subjects received a single dose of placebo administered SC Part A: SAD VIR-2218 50 mg VIR-2218 Healthy subjects received a single dose of VIR-2218 of 50 mg administered SC Part C: MAD Placebo Placebo Chronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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)
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
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.
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.
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
Trial Locations
- Locations (1)
Investigative Site
🇹🇭Khon Kaen, Thailand