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

A Phase 2 Randomized, Placebo-Controlled Study in Mainland China to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-2218

This study is to evaluate the safety, pharmacokinetics characteristics, and antiviral activities of multiple doses of VIR-2218 in adults with chronic HBV infection in mainland China.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: VIR-2218; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Investigative Site
  • Jilin
    • Changchun, Jilin, China
      • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female age 18 - 65;
• Weight ≥ 40 kg to ≤ 125 kg;
• Chronic HBV infection as defined by a positive serum HBsAg 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VIR-2218; Drug: VIR-2218 VIR-2218 given by subcutaneous injection	Drug: VIR-2218; VIR-2218 given by subcutaneous injection
Placebo Comparator: Placebo; Drug: Placebo Saline given by subcutaneous injection	Drug: Placebo; Saline given by subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-emergent Adverse Events (TEAEs)	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.	up to 48 weeks
Clinical Assessments Including But Not Limited to Laboratory Test Results	Number of participants with graded hematology, coagulation, chemistry abnormalities, and clinically significant abnormalities in vital signs and ECGs	up to 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK: Maximum Plasma Concentration	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.	Maximum plasma concentrations were calculated based on all above results for Day 1 and Day 29 (Week 4).
PK: Time to Reach Maximum Plasma Concentration	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.	Time to Cmax were calculated based on all above results for Day 1 and Day 29 (Week 4).
PK: Area Under the Plasma Concentration Versus Time Curve to Last Measurable Timepoint	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.	Area under the curve were calculated based on all above results for Day 1 and Day 29 (Week 4).
PK: Area Under the Plasma Concentration Versus Time Curve to Infinity	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.	Area under the curve were calculated based on all above results for Day 1 and Day 29 (Week 4).
PK: Percent of Area Extrapolated From AUC Last to Infinity	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.	Percent of area extrapolated from AUC last to infinity were calculated based on all above results for Day 1 and Day 29 (Week 4).
PK: Apparent Terminal Elimination Half-life	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.	Apparent terminal elimination half-life were calculated based on all above results for Day 1 and Day 29 (Week 4).
PK: Apparent Plasma Clearance	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.	Apparent plasma clearance were calculated based on all above results for Day 1 and Day 29 (Week 4).
PK: Apparent Volume of Distribution	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.	Apparent volume of distribution were calculated based on all above results for Day 1 and Day 29 (Week 4).
Maximum Change of Serum HBsAg From Baseline	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)	up to 16 weeks
Number of Participants With Serum HBsAg Loss	Number of participants with serum HBsAg < 0.05 IU/mL at two or more consecutive measurements	up to 48 weeks
Number of Participants With Sustained Serum HBsAg Loss for at Least 6 Months	Number of participants with sustained serum HBsAg < 0.05 IU/mL at all visits for at least 6 months	up to 48 weeks
Number of Participants With Anti-HBs Seroconversion at Any Timepoint	Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements	up to 48 weeks
For HBeAg-positive Subjects: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint	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.	up to 48 weeks

Collaborators and Investigators

• Sponsor: Brii Biosciences Limited
• Collaborators: Alnylam Pharmaceuticals; Vir Biotechnology, Inc.
• Investigators: Study Director: Xiaofei Chen, Brii Biosciences Limited

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: August 7, 2020
• First Submitted That Met QC Criteria: August 7, 2020
• First Posted (Actual): August 11, 2020

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: August 1, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Hepatitis; HBV; Chronic Hepatitis B; Hepatitis B Virus
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic
• Other Study ID Numbers: VIR-2218-1005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes