Trial Outcomes & Findings for Study of VIR-2218 in Patients With Chronic Hepatitis B in Mainland China (NCT NCT04507269)

NCT ID: NCT04507269

Last Updated: 2024-08-26

Results Overview

Number of participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0 are summarized by cohort. Incidence is defined as the number of participants with TEAEs in relation to the total number of participants in the cohort. TEAEs are defined as any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 21 participants
• Primary outcome timeframe: up to 48 weeks
• Results posted on: 2024-08-26

Participant Flow

Participant milestones

Measure	Part 1: VIR-2218 50 mg HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered 4 weeks apart	Part 1: VIR-2218 100 mg HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered 4 weeks apart	Part 1: Placebo HBeAg negative, participants received 2 SC doses of placebo administered 4 weeks apart	Part 2: VIR-2218 50mg HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered 4 weeks apart
Overall Study STARTED	4	4	3	4	4	2
Overall Study Dosed	4	4	3	4	4	2
Overall Study COMPLETED	3	3	3	4	3	2
Overall Study NOT COMPLETED	1	1	0	0	1	0

Reasons for withdrawal

Measure	Part 1: VIR-2218 50 mg HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered 4 weeks apart	Part 1: VIR-2218 100 mg HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered 4 weeks apart	Part 1: Placebo HBeAg negative, participants received 2 SC doses of placebo administered 4 weeks apart	Part 2: VIR-2218 50mg HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered 4 weeks apart
Overall Study Withdrawal by Subject	1	1	0	0	0	0
Overall Study Lost to Follow-up	0	0	0	0	1	0

Baseline Characteristics

Study of VIR-2218 in Patients With Chronic Hepatitis B in Mainland China

Baseline characteristics by cohort

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=3 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo n=2 Participants HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart	Total n=21 Participants Total of all reporting groups
Age, Continuous	48.5 years STANDARD_DEVIATION 9.68 • n=5 Participants	36.5 years STANDARD_DEVIATION 9.26 • n=7 Participants	31.0 years STANDARD_DEVIATION 5.20 • n=5 Participants	41.8 years STANDARD_DEVIATION 4.27 • n=4 Participants	39.5 years STANDARD_DEVIATION 10.66 • n=21 Participants	38.0 years STANDARD_DEVIATION 11.31 • n=10 Participants	39.7 years STANDARD_DEVIATION 9.26 • n=115 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	3 Participants n=115 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=10 Participants	18 Participants n=115 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants	2 Participants n=10 Participants	21 Participants n=115 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Region of Enrollment China	4 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants	4 participants n=21 Participants	2 participants n=10 Participants	21 participants n=115 Participants
Baseline log10 hepatitis B surface antigen	2.815 log10 IU/mL STANDARD_DEVIATION 0.4865 • n=5 Participants	3.278 log10 IU/mL STANDARD_DEVIATION 0.7910 • n=7 Participants	2.948 log10 IU/mL STANDARD_DEVIATION 0.4822 • n=5 Participants	3.598 log10 IU/mL STANDARD_DEVIATION 0.5479 • n=4 Participants	3.243 log10 IU/mL STANDARD_DEVIATION 0.4848 • n=21 Participants	3.722 log10 IU/mL STANDARD_DEVIATION 0.0729 • n=10 Participants	3.239 log10 IU/mL STANDARD_DEVIATION 0.5756 • n=115 Participants

PRIMARY outcome

Timeframe: up to 48 weeks

Population: All randomized participants who received at least 1 dose of study drug

Number of participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0 are summarized by cohort. Incidence is defined as the number of participants with TEAEs in relation to the total number of participants in the cohort. TEAEs are defined as any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug.

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=3 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo n=2 Participants HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
Incidence of Treatment-emergent Adverse Events (TEAEs) Any TEAEs	1 Participants	2 Participants	0 Participants	2 Participants	1 Participants	1 Participants
Incidence of Treatment-emergent Adverse Events (TEAEs) Any TEAEs of CTCAE Grade 1	0 Participants	1 Participants	0 Participants	2 Participants	1 Participants	1 Participants
Incidence of Treatment-emergent Adverse Events (TEAEs) Any TEAEs of CTCAE Grade 2	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Incidence of Treatment-emergent Adverse Events (TEAEs) Any TEAEs of CTCAE Grade 3 or above	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Incidence of Treatment-emergent Adverse Events (TEAEs) Any drug related TEAEs	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Incidence of Treatment-emergent Adverse Events (TEAEs) Any serious TEAEs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: up to 48 weeks

Population: All randomized participants who received at least 1 dose of study drug

Number of participants with graded hematology, coagulation, chemistry abnormalities, and clinically significant abnormalities in vital signs and ECGs

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=3 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo n=2 Participants HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
Clinical Assessments Including But Not Limited to Laboratory Test Results Any post baseline laboratory abnormalities of CTCAE Grade 1	4 Participants	4 Participants	2 Participants	2 Participants	4 Participants	2 Participants
Clinical Assessments Including But Not Limited to Laboratory Test Results Any post baseline laboratory abnormalities of CTCAE Grade 2 or above	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinical Assessments Including But Not Limited to Laboratory Test Results Any clinically significant vital signs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinical Assessments Including But Not Limited to Laboratory Test Results Any clinically significant ECGs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Maximum plasma concentrations were calculated based on all above results for Day 1 and Day 29 (Week 4).

Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter

VIR-2218 and metabolite maximum plasma concentrations (ng/mL)

VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=4 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
PK: Maximum Plasma Concentration VIR-2218 Cmax (Day 1)	120 ng/mL Geometric Coefficient of Variation 40.5	144 ng/mL Geometric Coefficient of Variation 100.5	65.8 ng/mL Geometric Coefficient of Variation 58.6	260 ng/mL Geometric Coefficient of Variation 90.4	—	—
PK: Maximum Plasma Concentration VIR-2218 Cmax (Day 29)	125 ng/mL Geometric Coefficient of Variation 48.8	198 ng/mL Geometric Coefficient of Variation 52.9	76.5 ng/mL Geometric Coefficient of Variation 35.7	268 ng/mL Geometric Coefficient of Variation 43.0	—	—
PK: Maximum Plasma Concentration AS(N-1)3'VIR-2218 Cmax (Day 1)	10.2 ng/mL Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	31.4 ng/mL Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	—	28.1 ng/mL Geometric Coefficient of Variation 171.1	—	—
PK: Maximum Plasma Concentration AS(N-1)3'VIR-2218 Cmax (Day 29)	16.3 ng/mL Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	23.6 ng/mL Geometric Coefficient of Variation 48.8	9.75 ng/mL Geometric Coefficient of Variation 1.1	19.3 ng/mL Geometric Coefficient of Variation 82.1	—	—

SECONDARY outcome

Timeframe: Time to Cmax were calculated based on all above results for Day 1 and Day 29 (Week 4).

Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter

VIR-2218 and metabolite time to Cmax (h)

VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=4 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
PK: Time to Reach Maximum Plasma Concentration VIR-2218 Tmax (Day 1)	4.99 hour Interval 1.88 to 8.03	2.00 hour Interval 0.967 to 8.08	4.02 hour Interval 4.0 to 7.8	4.00 hour Interval 4.0 to 7.58	—	—
PK: Time to Reach Maximum Plasma Concentration VIR-2218 Tmax (Day 29)	7.76 hour Interval 1.08 to 8.13	4.02 hour Interval 2.0 to 7.85	2.50 hour Interval 0.967 to 4.0	5.93 hour Interval 1.0 to 8.02	—	—
PK: Time to Reach Maximum Plasma Concentration AS(N-1)3'VIR-2218 Tmax (Day 1)	7.95 hour Interval 3.98 to 8.05	4.98 hour Interval 2.03 to 7.92	7.80 hour Interval 7.8 to 7.8	5.79 hour Interval 4.0 to 22.1	—	—
PK: Time to Reach Maximum Plasma Concentration AS(N-1)3'VIR-2218 Tmax (Day 29)	7.76 hour Interval 4.05 to 8.13	5.93 hour Interval 2.0 to 8.03	4.00 hour Interval 4.0 to 4.0	5.93 hour Interval 4.0 to 8.02	—	—

SECONDARY outcome

Timeframe: Area under the curve were calculated based on all above results for Day 1 and Day 29 (Week 4).

Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter

VIR-2218 and metabolite area under the curve from time 0 to last measurable time (ng*h/mL)

VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=4 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint VIR-2218 AUClast (Day 1)	1080 ng*h/mL Geometric Coefficient of Variation 25.3	1400 ng*h/mL Geometric Coefficient of Variation 115.6	626 ng*h/mL Geometric Coefficient of Variation 31.1	3190 ng*h/mL Geometric Coefficient of Variation 42.3	—	—
PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint VIR-2218 AUClast (Day 29)	854 ng*h/mL Geometric Coefficient of Variation 34.2	2390 ng*h/mL Geometric Coefficient of Variation 26.6	580 ng*h/mL Geometric Coefficient of Variation 56.9	3140 ng*h/mL Geometric Coefficient of Variation 15.8	—	—
PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint AS(N-1)3'VIR-2218 AUClast (Day 1)	58.7 ng*h/mL Geometric Coefficient of Variation 28.9	159 ng*h/mL Geometric Coefficient of Variation 30.5	67.6 ng*h/mL Geometric Coefficient of Variation 2.1	180 ng*h/mL Geometric Coefficient of Variation 63.4	—	—
PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint AS(N-1)3'VIR-2218 AUClast (Day 29)	50.2 ng*h/mL Geometric Coefficient of Variation 52.5	140 ng*h/mL Geometric Coefficient of Variation 81.2	63.1 ng*h/mL Geometric Coefficient of Variation 6.1	155 ng*h/mL Geometric Coefficient of Variation 39.8	—	—

SECONDARY outcome

Timeframe: Area under the curve were calculated based on all above results for Day 1 and Day 29 (Week 4).

Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter

VIR-2218 and metabolite area under the curve from time 0 to infinity (ng*h/mL)

VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=4 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
PK: Area Under the Plasma Concentration Versus Time Curve to Infinity VIR-2218 AUCinf (Day 1)	—	2820 ng*h/mL Geometric Coefficient of Variation 16.7	—	—	—	—
PK: Area Under the Plasma Concentration Versus Time Curve to Infinity VIR-2218 AUCinf (Day 29)	—	2570 ng*h/mL Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	1210 ng*h/mL Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	3530 ng*h/mL Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	—	—

SECONDARY outcome

Timeframe: Percent of area extrapolated from AUC last to infinity were calculated based on all above results for Day 1 and Day 29 (Week 4).

Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter

VIR-2218 and metabolite percent of area extrapolated from AUC last to infinity (%)

VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=4 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
PK: Percent of Area Extrapolated From AUC Last to Infinity VIR-2218 %AUCextrap (Day 1)	—	2.69 % of AUCinf Geometric Coefficient of Variation 5.1	—	—	—	—
PK: Percent of Area Extrapolated From AUC Last to Infinity VIR-2218 %AUCextrap (Day 29)	46.2 % of AUCinf Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	13.8 % of AUCinf Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	23.9 % of AUCinf Geometric Coefficient of Variation 263.4	5.88 % of AUCinf Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	—	—
PK: Percent of Area Extrapolated From AUC Last to Infinity AS(N-1)3'VIR-2218 %AUCextrap (Day 29)	—	49.2 % of AUCinf Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	—	—	—	—

SECONDARY outcome

Timeframe: Apparent terminal elimination half-life were calculated based on all above results for Day 1 and Day 29 (Week 4).

Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter

VIR-2218 and metabolite apparent terminal elimination half-life (h)

VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=4 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
PK: Apparent Terminal Elimination Half-life VIR-2218 t1/2 (Day 1)	—	4.16 hour Interval 4.1 to 4.22	—	—	—	—
PK: Apparent Terminal Elimination Half-life VIR-2218 t1/2 (Day 29)	—	7.66 hour Interval 7.66 to 7.66	6.53 hour Interval 6.53 to 6.53	5.49 hour Interval 5.49 to 5.49	—	—

SECONDARY outcome

Timeframe: Apparent plasma clearance were calculated based on all above results for Day 1 and Day 29 (Week 4).

Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter

VIR-2218 and metabolite apparent plasma clearance CL/F (mL/h)

VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=4 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
PK: Apparent Plasma Clearance VIR-2218 CL/F (Day 1)	—	35400 mL/h Geometric Coefficient of Variation 16.7	—	—	—	—
PK: Apparent Plasma Clearance VIR-2218 CL/F (Day 29)	—	39000 mL/h Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	41300 mL/h Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	28300 mL/h Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	—	—

SECONDARY outcome

Timeframe: Apparent volume of distribution were calculated based on all above results for Day 1 and Day 29 (Week 4).

Population: All randomized participants who received at least 1 dose of VIR-2218 and had 1 post-baseline PK parameter

VIR-2218 and metabolite apparent volume of distribution Vz/F (mL)

VIR-2218 and metabolite concentrations were tested at predose on Day 1 and 1h, 2h, 4h, 8h, and 24h postdose, Week 1, predose on Week 4 and 1h, 2h, 4h, 8h, and 24h postdose, Week 5, Week 8, Week 16, and Week 24.

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=4 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
PK: Apparent Volume of Distribution VIR-2218 Vz/F (Day 1)	—	213000 mL Geometric Coefficient of Variation 18.6	—	—	—	—
PK: Apparent Volume of Distribution VIR-2218 Vz/F (Day 29)	—	431000 mL Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	389000 mL Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	224000 mL Geometric Coefficient of Variation NA %Geometric CoV not reported; measurable in 1/4 participants	—	—

SECONDARY outcome

Timeframe: up to 16 weeks

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 non-missing data for antiviral parameters

Maximum change of serum HBsAg from Day 1 until 12 weeks post last dose (negative values mean reductions from baseline, positive values mean increased from baseline)

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=3 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo n=2 Participants HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
Maximum Change of Serum HBsAg From Baseline	-1.064 log10 IU/mL Standard Deviation 0.1047	-1.346 log10 IU/mL Standard Deviation 0.5169	-0.049 log10 IU/mL Standard Deviation 0.0158	-0.793 log10 IU/mL Standard Deviation 0.1017	-1.268 log10 IU/mL Standard Deviation 0.1693	-0.120 log10 IU/mL Standard Deviation 0.0826

SECONDARY outcome

Timeframe: up to 48 weeks

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 non-missing data for antiviral parameters

Number of participants with serum HBsAg < 0.05 IU/mL at two or more consecutive measurements

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=3 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo n=2 Participants HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
Number of Participants With Serum HBsAg Loss	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 48 weeks

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 non-missing data for antiviral parameters

Number of participants with sustained serum HBsAg < 0.05 IU/mL at all visits for at least 6 months

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=3 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo n=2 Participants HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
Number of Participants With Sustained Serum HBsAg Loss for at Least 6 Months	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 48 weeks

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 non-missing data for antiviral activity parameter

Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=3 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg n=4 Participants HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo n=2 Participants HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
Number of Participants With Anti-HBs Seroconversion at Any Timepoint	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 48 weeks

Population: Part 2 (HBeAg positive) participants only; all randomized participants who received at least 1 dose of study drug and had at least 1 non-missing data for antiviral activity parameter

HBeAg loss is defined as quantitative HBeAg < 0.14 IU/mL at two or more consecutive measurements. Anti-HBe seroconversion is defined as anti-HBe positivity at two or more consecutive measurements.

Outcome measures

Measure	Part 1: VIR-2218 50 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg n=4 Participants HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=2 Participants HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint HBeAg loss	0 Participants	0 Participants	0 Participants	—	—	—
For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint Anti-HBe seroconversion	0 Participants	0 Participants	0 Participants	—	—	—

Adverse Events

Part 1: VIR-2218 50 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 1: VIR-2218 100 mg 100 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part 1: Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 2: VIR-2218 50 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part 2: VIR-2218 100 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 2: Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Part 1: VIR-2218 50 mg n=4 participants at risk HBeAg negative, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 1: VIR-2218 100 mg 100 mg n=4 participants at risk HBeAg negative, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 1: Placebo n=3 participants at risk HBeAg negative, participants received 2 SC doses of placebo administered every 4 weeks apart	Part 2: VIR-2218 50 mg n=4 participants at risk HBeAg positive, participants received 2 SC doses of VIR-2218 50 mg administered every 4 weeks apart	Part 2: VIR-2218 100 mg n=4 participants at risk HBeAg positive, participants received 2 SC doses of VIR-2218 100 mg administered every 4 weeks apart	Part 2: Placebo n=2 participants at risk HBeAg positive, participants received 2 SC doses of placebo administered every 4 weeks apart
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/3 • Up to 48 weeks after the first dose of VIR-2218 or placebo	25.0% 1/4 • Number of events 1 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/2 • Up to 48 weeks after the first dose of VIR-2218 or placebo
Gastrointestinal disorders Epigastric discomfort	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/3 • Up to 48 weeks after the first dose of VIR-2218 or placebo	25.0% 1/4 • Number of events 1 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/2 • Up to 48 weeks after the first dose of VIR-2218 or placebo
Gastrointestinal disorders Toothache	25.0% 1/4 • Number of events 1 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/3 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/2 • Up to 48 weeks after the first dose of VIR-2218 or placebo
Metabolism and nutrition disorders Decreased appetite	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/3 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	25.0% 1/4 • Number of events 1 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/2 • Up to 48 weeks after the first dose of VIR-2218 or placebo
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/3 • Up to 48 weeks after the first dose of VIR-2218 or placebo	25.0% 1/4 • Number of events 2 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/2 • Up to 48 weeks after the first dose of VIR-2218 or placebo
General disorders Fatigue	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/3 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	25.0% 1/4 • Number of events 2 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/2 • Up to 48 weeks after the first dose of VIR-2218 or placebo
Infections and infestations Upper respiratory tract infection	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	25.0% 1/4 • Number of events 1 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/3 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/2 • Up to 48 weeks after the first dose of VIR-2218 or placebo
Injury, poisoning and procedural complications Animal bite	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	25.0% 1/4 • Number of events 1 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/3 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/2 • Up to 48 weeks after the first dose of VIR-2218 or placebo
Nervous system disorders Somnolence	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/3 • Up to 48 weeks after the first dose of VIR-2218 or placebo	25.0% 1/4 • Number of events 1 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/2 • Up to 48 weeks after the first dose of VIR-2218 or placebo
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/3 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	0.00% 0/4 • Up to 48 weeks after the first dose of VIR-2218 or placebo	50.0% 1/2 • Number of events 1 • Up to 48 weeks after the first dose of VIR-2218 or placebo

Additional Information

Clinical Research

Brii Biosciences Limited

Phone: 86 10 6299 8808

Email: clinicaltrials@briibio.com

Results disclosure agreements

• Principal investigator is a sponsor employee Investigator will submit the proposed publication to sponsor at least 60 days prior to submission to a publisher. Sponsor shall advise investigator any information that are confidential or may impair the availability of patent protection for study inventions. Sponsor may require to remove confidential information and/or to delay the proposed publication or presentation for an additional 60 days to seek patent protection for study inventions.
• Publication restrictions are in place

Restriction type: OTHER