CompletedNCT03672188Updated Dec 13, 2021Results posted

Study of VIR-2218 in Healthy Subjects and Patients With Chronic Hepatitis B

A Phase 1/2 interventional study of VIR-2218 and Placebo in Chronic Hepatitis B, sponsored by Vir Biotechnology, Inc.. Completed at 14 sites in 5 countries. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-12-13.

Sponsored by Vir Biotechnology, Inc. · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 82
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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.

Conditions studied

Chronic Hepatitis B

Browse trials for

Keywords

Hepatitis B Virus
Chronic Hepatitis B
HBV
Hepatitis

In context

Hepatitis A

2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.

This study's enrollment of 82 is below the median of 100 across 1,886 interventional studies indexed under Hepatitis A.

Browse Hepatitis A studies →

Lead sponsor

Vir Biotechnology, Inc. is the lead sponsor of 21 studies on the registry; 2 are open to participants now.

Of its 14 completed or terminated interventional studies of FDA-regulated products, 10 (71%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Eligibility 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

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

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 82 participants (actual)

Study arms

Experimental
Part A: SAD VIR-2218 50 mg
Healthy subjects received a single dose of VIR-2218 of 50 mg administered SC
Drug: VIR-2218
Experimental
Part A: SAD VIR-2218 100 mg
Healthy subjects received a single dose of VIR-2218 of 100 mg administered SC
Drug: VIR-2218
Experimental
Part A: SAD VIR-2218 200 mg
Healthy subjects received a single dose of VIR-2218 of 200 mg administered SC
Drug: VIR-2218
Experimental
Part A: SAD VIR-2218 400 mg
Healthy subjects received a single dose of VIR-2218 of 400 mg administered SC
Drug: VIR-2218
Experimental
Part A: SAD VIR-2218 600 mg
Healthy subjects received a single dose of VIR-2218 of 600 mg administered SC
Drug: VIR-2218
Experimental
Part A: SAD VIR-2218 900 mg
Healthy subjects received a single dose of VIR-2218 of 900 mg administered SC
Drug: VIR-2218
Placebo comparator
Part A: SAD Placebo
Healthy subjects received a single dose of placebo administered SC
Drug: Placebo
Experimental
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.
Drug: VIR-2218
Experimental
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.
Drug: VIR-2218
Experimental
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.
Drug: VIR-2218
Experimental
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.
Drug: VIR-2218
Experimental
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.
Drug: VIR-2218
Experimental
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.
Drug: VIR-2218
Placebo comparator
Part B: MAD Placebo
Chronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart.
Drug: Placebo
Placebo comparator
Part C: MAD Placebo
Chronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.
Drug: Placebo

Interventions

DrugVIR-2218
VIR-2218 given by subcutaneous injection
DrugPlacebo
Sterile normal saline (0.9% NaCl) given by subcutaneous injection

What researchers measure

Primary outcomes

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

Secondary outcomes

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
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

Results

Posted Dec 13, 2021

Participant flow

Participant flow — Overall Study
Milestone	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 200 mg	Part B: MAD Placebo	Part C: MAD Placebo
Started	6	6	6	8	6	6	12	3	6	6	3	3	3	6	2
Dosed	6	6	6	7	6	6	12	3	6	6	3	3	3	6	2
Completed	6	6	5	5	6	6	12	3	6	6	3	3	2	6	2
Not completed	0	0	1	3	0	0	0	0	0	0	0	0	1	0	0
Withdrew: Withdrawal by subject	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0
Withdrew: Death	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Withdrew: Lost to follow-up	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0

Outcome measures

PrimaryIncidence 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
Reported as:: Count of participants · Participants

Incidence of Adverse Events (AEs)
Participants	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-2219 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
Incidence of Adverse Events (AEs)	4	3	4	5	3	3	6	0	2	5	2	2	2	1	1

PrimaryClinical 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
Reported as:: Count of participants · Participants

Clinical Assessments Including But Not Limited to Laboratory Test Results
Participants	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
CTCAE v5.0 Lab Grade 0	1	1	1	1	1	0	1	1	0	0	0	0	0	1	0
CTCAE v5.0 Lab Grade 1	3	3	3	4	4	3	7	2	4	5	3	3	3	3	2
CTCAE v5.0 Lab Grade 2	1	2	1	1	1	3	3	0	2	1	0	0	0	2	0
CTCAE v5.0 Lab Grade 3	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0
CTCAE v5.0 Lab Grade 4	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Clinically Significant Vital Signs	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Clinically Significant ECG	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

SecondaryMaximum 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
Reported as:: Mean · ng/mL

Maximum Plasma Concentration (ng/mL)
ng/mL	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 B/C: MAD VIR-2218 20 mg	Part B/C: MAD VIR-2218 50 mg	Part B/C: MAD VIR-2218 100 mg	Parts B/C: MAD VIR-2218 200 mg
VIR-2218 Cmax (Day 1)	155 ± 65.3	355 ± 117	711 ± 207	2110 ± 722	1830 ± 615	5010 ± 630	73.5 ± NA	118 ± 61.2	235 ± 79.0	826 ± 336
AS (N-1)3' VIR-2218 Cmax (Day 1)	NA ± NA	40.5 ± NA	62.4 ± 17.6	259 ± 114	177 ± 99.2	514 ± 106	NA ± NA	NA ± NA	NA ± NA	66.1 ± NA
VIR-2218 Cmax (Day 29)	—	—	—	—	—	—	51.8 ± 21.1	115 ± 38.2	256 ± 167	807 ± 374
AS (N-1)3' VIR-2218 Cmax (Day 29)	—	—	—	—	—	—	NA ± NA	NA ± NA	NA ± NA	75.1 ± 27.2

SecondaryTime 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
Reported as:: Median · h

Time to Reach Maximum Plasma Concentration (h)
h	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 B/C: MAD VIR-2218 20 mg	Part B/C: MAD VIR-2218 50 mg	Part B/C: MAD VIR-2218 100 mg	Part B/C: MAD VIR-2218 200 mg
VIR-2218 Tmax Day 1	4.25 (1.17 to 4.25)	4.32 (4.25 to 6.17)	5.21 (4.25 to 6.18)	7.21 (4.25 to 8.25)	7.21 (6.17 to 10.2)	4.25 (4.25 to 8.25)	4.00 (4.00 to 8.02)	7.63 (4.00 to 7.93)	2.48 (1.00 to 7.97)	5.98 (3.98 to 8.00)
AS(N-1)3' VIR-2218 Tmax Day 1	NA (NA to NA)	6.17 (4.25 to 6.17)	6.17 (4.25 to 6.18)	9.21 (4.25 to 10.2)	10.2 (8.25 to 10.2)	8.25 (4.25 to 10.2)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	8.00 (7.97 to 8.00)
VIR-2218 Tmax Day 29	—	—	—	—	—	—	3.95 (0.92 to 4.00)	4.00 (4.00 to 7.98)	8.00 (4.00 to 8.00)	3.99 (2.00 to 8.00)
AS (N-1)3' VIR-2218 Tmax Day 29	—	—	—	—	—	—	NA (NA to NA)	NA (NA to NA)	6.00 (4.00 to 8.00)	5.99 (4.00 to 8.00)

SecondaryArea 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
Reported as:: Mean · h*ng/mL

Area Under the Plasma Concentration Versus Time Curve (ng*h/mL)
h*ng/mL	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 B/C: MAD VIR-2218 20mg	Part B/C: MAD VIR-2218 50 mg	Part B/C: MAD VIR-2218 100 mg	Part B/C: MAD VIR-2218 200 mg
VIR-2218 AUClast (Day 1)	1270 ± 270	3740 ± 1190	6630 ± 1160	23500 ± 2700	27900 ± 7540	58800 ± 9070	360 ± 199	1000 ± 285	2700 ± 943	9570 ± 2410
AS(N-1) 3' VIR-2218 AUClast (Day 1)	NA ± NA	208 ± 190	481 ± 149	2530 ± 613	2680 ± 1460	6430 ± 1500	NA ± NA	NA ± NA	NA ± NA	482 ± 199
VIR-2218 AUClast (Day 29)	—	—	—	—	—	—	339 ± 171	910 ± 326	2550 ± 638	9580 ± 3240
AS(N-1) 3' VIR-2218AUClast (Day 29)	—	—	—	—	—	—	NA ± NA	NA ± NA	174 ± NA	393 ± 230

SecondaryApparent 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
Reported as:: Median · h

Apparent Terminal Elimination Half-life (h)
h	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
Apparent Terminal Elimination Half-life (h)	2.45 (2.35 to 3.26)	3.64 (3.49 to 4.95)	4.38 (4.22 to 6.11)	3.54 (2.49 to 5.51)	5.28 (5.12 to 5.62)	4.55 (3.25 to 4.69)

SecondaryApparent 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
Reported as:: Mean · L/h

Apparent Plasma Clearance (L/h)
L/h	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
Apparent Plasma Clearance (L/h)	34.0 ± 2.54	21.8 ± 4.27	30.8 ± 4.51	16.8 ± 1.76	21.9 ± 6.91	15.3 ± 2.08

SecondaryApparent 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
Reported as:: Mean · L

Apparent Volume of Distribution (L)
L	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
Apparent Volume of Distribution (L)	155 ± 69.7	132 ± 40.7	223 ± 76.0	104 ± 62.6	176 ± 60.8	92.9 ± 24.6

SecondaryUrine %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)
Reported as:: Mean · % excreted in the urine from time 0-24h

Urine %fe 0-24h
% excreted in the urine from time 0-24h	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
VIR-2218 fe 0-24	16.9 ± 3.19	21.7 ± 6.22	23.2 ± 4.34	29.5 ± 5.72	32.3 ± 11.7	47.6 ± 8.59
AS(N-1)3' VIR-2218 fe 0-24	1.94 ± 0.480	4.16 ± 2.28	3.31 ± 0.656	4.99 ± 0.740	4.12 ± 2.31	6.96 ± 1.47

SecondaryApparent 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)
Reported as:: Mean · L/h

Apparent Renal Clearance (CLR/F)
L/h	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
Apparent Renal Clearance (CLR/F)	5.87 ± 0.728	5.22 ± 1.27	7.00 ± 0.659	5.13 ± 0.850	7.22 ± 1.480	7.47 ± 1.340

SecondaryMaximum Reduction of Serum HBsAg From Baseline

Maximum reduction of serum HBsAg from Day 1 until Week 16.

Time frame:: Up to 112 days
Reported as:: Mean · log10 IU/mL

Maximum Reduction of Serum HBsAg From Baseline
log10 IU/mL	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
Maximum Reduction of Serum HBsAg From Baseline	-1.031 ± 0.574	-1.230 ± 0.702	-1.504 ± 0.540	-1.653 ± 0.154	-1.161 ± 0.350	-1.568 ± 0.636	-0.098 ± 0.047	-0.068 ± 0.01

SecondaryNumber 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
Reported as:: Count of participants · Participants

Number of Subjects With Serum HBsAg Loss at Any Time Point
Participants	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
Number of Subjects With Serum HBsAg Loss at Any Time Point	0	0	0	0	0	0	0	0

SecondaryNumber 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
Reported as:: Count of participants · Participants

Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months
Participants	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
Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months	0	0	0	0	0	0	0	0

SecondaryNumber 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
Reported as:: Count of participants · Participants

Number of Subjects With Anti-HBs Seroconversion at Any Timepoint
Participants	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
Number of Subjects With Anti-HBs Seroconversion at Any Timepoint	0	0	0	0	0	0	0	0

SecondaryNumber 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
Reported as:: Count of participants · Participants

Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint
Participants	Part C MAD: VIR-2218 50 mg	Part C MAD: VIR-2218 200 mg	Part C MAD: Placebo
Number of Subjects with HBeAg Loss	0	1	0
Number of Subjects with anti-HBe seroconversion	0	1	0

Adverse events

Collected over Up to 364 days after first dose with VIR-2218 or placebo. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part A SAD: VIR-2218 50 mg	0/6 (0%)	0/6 (0%)	4/6 (66.7%)
Part A SAD: VIR-2218 100 mg	0/6 (0%)	0/6 (0%)	3/6 (50%)
Part A SAD: VIR-2218 200 mg	0/6 (0%)	0/6 (0%)	4/6 (66.7%)
Part A SAD: VIR-2218 400 mg	0/7 (0%)	0/7 (0%)	5/7 (71.4%)
Part A SAD: VIR-2218 600 mg	0/6 (0%)	0/6 (0%)	3/6 (50%)
Part A SAD: VIR-2218 900 mg	0/6 (0%)	0/6 (0%)	3/6 (50%)
Part A SAD: Placebo	0/12 (0%)	0/12 (0%)	6/12 (50%)
Part B MAD: VIR-2218 20 mg	0/3 (0%)	0/3 (0%)	0/3 (0%)
Part B MAD: VIR-2218 50 mg	0/6 (0%)	0/6 (0%)	2/6 (33.3%)
Part B MAD: VIR-2218 100 mg	0/6 (0%)	1/6 (16.7%)	5/6 (83.3%)
Part B MAD: VIR-2218 200 mg	0/3 (0%)	0/3 (0%)	2/3 (66.7%)
Part C MAD: VIR-2218 50 mg	0/3 (0%)	0/3 (0%)	2/3 (66.7%)
Part C MAD: VIR-2218 200 mg	1/3 (33.3%)	0/3 (0%)	2/3 (66.7%)
Part B MAD: Placebo	0/6 (0%)	0/6 (0%)	1/6 (16.7%)
Part C MAD: Placebo	0/2 (0%)	0/2 (0%)	1/2 (50%)

Most frequent serious events

Most frequent serious events
Event	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
HeadacheNervous system disorders	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

Most frequent other events

Showing 10 of 47

Most frequent other events
Event	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
Cardiac murmurInvestigations	0/6	0/6	0/6	0/7	0/6	0/6	0/12	0/3	0/6	0/6	0/3	0/3	0/3	0/6	1/2
HeadacheNervous system disorders	1/6	3/6	2/6	2/7	0/6	1/6	2/12	0/3	1/6	2/6	1/3	1/3	1/3	0/6	0/2
PalpitationsCardiac disorders	0/6	0/6	0/6	0/7	0/6	0/6	0/12	0/3	0/6	0/6	0/3	1/3	0/3	0/6	0/2
ToothacheGastrointestinal disorders	0/6	0/6	0/6	0/7	0/6	0/6	0/12	0/3	0/6	0/6	1/3	0/3	0/3	0/6	0/2
FatigueGeneral disorders	0/6	0/6	0/6	0/7	0/6	0/6	0/12	0/3	0/6	2/6	0/3	0/3	0/3	0/6	0/2
Influenza like illnessGeneral disorders	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
Injection site bruisingGeneral disorders	0/6	0/6	0/6	0/7	1/6	2/6	0/12	0/3	0/6	0/6	0/3	1/3	0/3	0/6	0/2
ContusionInjury, poisoning and procedural complications	0/6	0/6	0/6	0/7	0/6	1/6	0/12	0/3	0/6	0/6	0/3	1/3	0/3	0/6	0/2
MyalgiaMusculoskeletal and connective tissue disorders	0/6	0/6	0/6	0/7	0/6	0/6	0/12	0/3	0/6	1/6	0/3	0/3	1/3	0/6	0/2
DizzinessNervous system disorders	0/6	0/6	0/6	0/7	0/6	0/6	1/12	0/3	0/6	2/6	0/3	0/3	0/3	0/6	0/2

Baseline characteristics

The Overall Number of Baseline Participants 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.

Age, Continuous
Age, Continuous(Years)	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	Total
Mean	25 ± 3	23.3 ± 4	26.7 ± 3.8	24.3 ± 3.7	28.8 ± 6.3	32.5 ± 9.5	26.5 ± 6.7	40.3 ± 9.1	42.5 ± 10.8	45.2 ± 5.5	55 ± 4	35 ± 9.8	33.7 ± 13.1	44 ± 7.2	58.5 ± 7.8	33.4 ± 11.5

Sex: Female, Male
Sex: Female, Male(Participants)	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	Total
Female	6	4	3	7	3	3	5	1	1	1	3	2	1	3	1	44
Male	0	2	3	0	3	3	7	2	5	5	0	1	2	3	1	37

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	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	Total
Hispanic or Latino	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	2
Not Hispanic or Latino	6	6	6	7	6	5	11	3	6	6	3	3	3	6	2	79
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	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	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian	2	3	0	0	2	1	1	3	5	5	3	3	3	6	2	39
Native Hawaiian or Other Pacific Islander	1	1	0	1	0	0	2	0	1	0	0	0	0	0	0	6
Black or African American	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
White	2	2	5	5	3	3	8	0	0	1	0	0	0	0	0	29
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	1	0	1	1	1	2	1	0	0	0	0	0	0	0	0	7

Region of Enrollment
Region of Enrollment(participants)	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	Total
New Zealand	6	6	6	7	6	6	12	0	2	1	0	1	0	0	1	54
South Korea	0	0	0	0	0	0	0	1	1	2	2	1	0	1	0	8
Hong Kong	0	0	0	0	0	0	0	1	3	0	0	1	1	2	0	8
Australia	0	0	0	0	0	0	0	0	0	2	0	0	2	0	0	4
Thailand	0	0	0	0	0	0	0	1	0	1	1	0	0	3	1	7

Hepatitis B Surface Antigen Levels (IU/mL)
Hepatitis B Surface Antigen Levels (IU/mL)(IU/mL)	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	Total
Mean	—	—	—	—	—	—	—	2372.227 ± 1168.940	3872.625 ± 5678.292	4009.863 ± 5239.703	2374.423 ± 2078.034	3488.037 ± 2454.215	12640.983 ± 10495.983	4819.127 ± 6348.594	1886.045 ± 1223.655	4456.52 ± 5657.74

Alanine Aminotransferase Levels
Alanine Aminotransferase Levels(U/L)	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	Total
Mean	—	—	—	—	—	—	—	15.3 ± 4.6	23.5 ± 14.9	14.3 ± 5.0	10.0 ± 4.0	27.7 ± 18.6	26.0 ± 17.7	21.8 ± 17.6	26.5 ± 10.6	20.25 ± 13.08

Study locations

14 sites

Investigative Site
Birtinya, Queensland 4575, Australia
Investigative Site
Clayton, Victoria 3168, Australia
Investigative Site
Fitzroy, Victoria 3065, Australia
Investigative Site
Hong Kong, Hong Kong
Investigative Site
Busan, 49241, Korea, Republic of
Investigative Site
Seoul, 03080, Korea, Republic of
Investigative Site
Seoul, 05505, Korea, Republic of
Investigative Site
Auckland, 1010, New Zealand
Investigative Site
Auckland, 2025, New Zealand
Investigative Site
Bangkok, 10330, Thailand
Investigative Site
Bangkok, 10400, Thailand
Investigative Site
Bangkok, 10700, Thailand
Investigative Site
Hat Yai, 90110, Thailand
Investigative Site
Khon Kaen, 40002, Thailand

References and documents

Publications

Gupta SV, Fanget MC, MacLauchlin C, Clausen VA, Li J, Cloutier D, Shen L, Robbie GJ, Mogalian E. Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection. Drugs R D. 2021 Dec;21(4):455-465. doi: 10.1007/s40268-021-00369-w. Epub 2021 Nov 6. PubMed 34741731 ↗

Study documents

Study protocol · Mar 27, 2019
Statistical analysis plan · Dec 22, 2020

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 13, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03672188
Lead sponsor: Vir Biotechnology, Inc.
Collaborators: Alnylam Pharmaceuticals
Responsible party: Sponsor
First posted: Sep 14, 2018
Start date: Nov 14, 2018
Primary completion: Sep 3, 2020
Completion: Sep 3, 2020
Results posted: Dec 13, 2021
Last update: Dec 13, 2021

Oversight

FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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