Study of VIR-3434 in Healthy Volunteers and Patients With Chronic Hepatitis B Virus Infection

A Phase 1, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-3434

This is a Phase 1 study in which healthy volunteers and participants with chronic HBV infection will receive VIR-3434 or placebo and will be assessed for safety, tolerability, pharmacokinetics (PK), and antiviral activity (only in participants with chronic HBV infection).

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Biological: VIR-3434; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, 45147
    • Investigative Site
  • Frankfurt, Germany, 60590
    • Investigative Site
  • Hannover, Germany, 30625
    • Investigative Site
  • Leipzig, Germany, 04103
    • Investigative Site
  • Mainz, Germany, 55131
    • Investigative Site
  • Mannheim, Germany, 68167
    • Investigative Site
  • Ulm, Germany, 89081
    • Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Investigative Site
  • Busan, Korea, Republic of, 47392
    • Investigative Site
  • Seoul, Korea, Republic of, 03080
    • Investigative Site
  • Seoul, Korea, Republic of, 05505
    • Investigative Site
  • Seoul, Korea, Republic of, 02841
    • Investigative Site
  • Seoul, Korea, Republic of, 06273
    • Investigative Site
• New Zealand
  • Auckland, New Zealand, 1010
    • Investigative Site
  • Havelock North, New Zealand, 4130
    • Investigative Site
  • Newtown, New Zealand, 6021
    • Investigative Site
  • Tauranga, New Zealand, 3110
    • Investigative Site
• Romania
  • Bucharest, Romania
    • Investigative Site
• Singapore
  • Singapore, Singapore, 169608
    • Investigative Site
  • Singapore, Singapore, 529889
    • Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • Investigative Site
  • London, United Kingdom, E1 2EF
    • Investigative Site
  • Manchester, United Kingdom, M8 5RB
    • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Healthy Volunteers:

Inclusion Criteria:

• Male or female age 18 - 55
• Weight 40-125 kg

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 allergic reactions to monoclonal antibodies or antibody fragments
• History of anaphylaxis

CHB Patients:

Inclusion Criteria:

• Male or female age 18 - 65
• Weight 40-125 kg
• Chronic HBV infection for >/= 6 months

Exclusion Criteria:

• Any clinically significant chronic or acute medical condition that makes the participant unsuitable for participation
• Significant fibrosis or cirrhosis
• History or evidence of drug or alcohol abuse
• History of chronic liver disease from any cause other than chronic HBV infection
• History of hepatic decompensation
• History of anaphylaxis
• History of allergic reactions to monoclonal antibodies or antibody fragments
• History of immune complex disease
• Active infection with HIV, HCV or hepatitis Delta virus

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
Placebo Comparator: Placebo	Other: Placebo; Sterile normal saline (0.9% NaCl) given by subcutaneous injection or intravenous infusion.
Experimental: VIR-3434	Biological: VIR-3434; VIR-3434 given by subcutaneous injection or intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Treatment-emergent period, which is up to Week 24 in part A, and up to Week 8 in part B/C/D
Number of Participants With Clinical Laboratory Abnormalities	Up to 280 days post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	VIR-3434 Maximum Concentration in Serum	Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Tmax	VIR-3434 time of Cmax in Serum	Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
AUClast	VIR-3434 under the curve from time 0 to last measurable Time	Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
t1/2	VIR-3434 apparent Elimination Half-life (t1/2) in serum	Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Vz/F	VIR-3434 Volume of Distribution (SC only)	Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Vz	VIR-3434 Volume of Distribution (IV only)	Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose
CL/F	VIR-3434 Apparent serum clearance (SC only)	Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose; Parts B-D: pre-dose and 1, 4, 6, 24 hours, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
CL	VIR-3434 Apparent serum clearance (IV only)	Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose
Number of Participants With ADA to VIR-3434	Evaluate the immunogenicity of VIR-3434	Part A: Up to 168 days post-dose. Parts B-D: Up to 280 days post-dose
Maximum Reduction of Serum HBsAg From Baseline (Day 1 Predose)	HBsAg reductions at nadir and Week 4	Parts B-D: pre-dose and 1, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Part D Only: Maximum Change of HBV DNA From Baseline (Day 1 Predose)	HBV DNA reductions at nadir and Week 4	Parts B-D: pre-dose and 1, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose Parts B-D: pre-dose and 1, 3, 7, 10, 14, 28, 56, 84, 112, 168, 224, 280 days post-dose
Titers (if Applicable) of ADA to VIR-3434	Evaluate the immunogenicity of VIR-3434	Part A: Up to 168 days post-dose. Parts B-D: Up to 280 days post-dose
Cmax	VIR-3434 Maximum Concentration in Serum	Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose
AUClast	VIR-3434 under the curve from time 0 to last measurable Time	Part A: pre-dose and 1, 4, 6, 24 hours, 3, 7, 14, 28, 56, 84, 126, 168 days post-dose

Other Outcome Measures

Outcome Measure	Time Frame
Assessment of mean changes in HBV RNA levels	Up to 280 days post-dose
Assessment of mean changes in HBcrAg levels	Up to 280 days post-dose
Evaluation of host immune responses in peripheral blood, including analysis of circulating biomarkers and cellular immunity	Up to 280 days post-dose
Analysis and evaluation of host gene expression by RNA-sequencing	Up to 280 days post-dose
Fc gamma receptor (FcγR) polymorphisms as determined by genotyping	Day 1
IgG allotypes as determined by genotyping	Day 1

Collaborators and Investigators

• Sponsor: Vir Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2020
• Primary Completion (Actual): October 24, 2022
• Study Completion (Actual): November 25, 2022

Study Registration Dates

• First Submitted: May 25, 2020
• First Submitted That Met QC Criteria: June 4, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: September 27, 2024
• Last Verified: September 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; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: VIR-3434-1002; 2019-003837-40 (EudraCT Number)

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