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, 45122
    • 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
• 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
  • Tauranga, New Zealand, 3110
    • Investigative Site
  • Wellington, New Zealand, 6021
    • Investigative Site
• Romania
  • Bucharest, Romania
    • Investigative Site
• Singapore
  • Singapore, Singapore, 169608
    • Investigative Site
  • Singapore, Singapore, 529889
    • Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Investigative Site
  • London, United Kingdom, E1 1FR
    • 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: No
• Genders Eligible for Study: All

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	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)		Up to 280 days post-dose
Clinical assessment of changes in physical examinations		Up to 280 days post-dose
Clinical assessment and quantification of changes in vital signs: blood pressure		Up to 280 days post-dose
Clinical assessment and quantification of changes in vital signs: pulse rate		Up to 280 days post-dose
Clinical assessment and quantification of changes in vital signs: temperature		Up to 280 days post-dose
Clinical assessment and quantification of changes in vital signs: respiratory rate		Up to 280 days post-dose
Proportion of subjects with abnormalities in ECGs		Up to 280 days post-dose
Clinical assessment and quantification of changes in liver function tests	Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin	Up to 280 days post-dose
Clinical assessment and quantification of changes in serum chemistry parameters	Albumin, blood urea nitrogen, calcium, carbon dioxide/bicarbonate, chloride, creatine kinase, creatinine, creatinine clearance, gamma glutamyl transferase, glucose, lactate dehydrogenase, potassium, and sodium	Up to 280 days post-dose
Clinical assessment and quantification of changes in hematology parameters	Bands, basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, monocytes, neutrophils, platelets, red blood cells, and white blood cells	Up to 280 days post-dose
Clinical assessment and quantification of changes in coagulation parameters	INR and prothrombin time	Up to 280 days post-dose
Clinical assessment and quantification of changes in urinalysis parameters	Bilirubin, glucose, ketones, leukocytes, nitrite, pH, proteins, red blood cells, specific gravity, and urobilinogen	Up to 280 days post-dose
Clinical assessment and quantification of changes in complement	C3 and C4	Up to 280 days post-dose
Clinical assessment of changes in local tolerability using a numeric scoring tool that is based on FDA and DAIDs injection site reaction grading scales		Up to 280 days post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax	Up to 280 days post-dose
Clast	Up to 280 days post-dose
Tmax	Up to 280 days post-dose
Tlast	Up to 280 days post-dose
AUCinf	Up to 280 days post-dose
AUClast	Up to 280 days post-dose
%AUCexp	Up to 280 days post-dose
t1/2	Up to 280 days post-dose
λz	Up to 280 days post-dose
Vz (IV only)	Up to 280 days post-dose
CL (IV only)	Up to 280 days post-dose
Vz/F (SC only)	Up to 280 days post-dose
CL/F (SC only)	Up to 280 days post-dose
Incidence of ADA to VIR-3434	Up to 280 days post-dose
Titers of ADA to VIR-3434	Up to 280 days post-dose
Maximum reduction of serum HBsAg from baseline (Day 1 predose)	Up to 280 days post-dose
Part D only: maximum change of HBV DNA from baseline (Day 1 predose)	Up to 280 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): December 19, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Hepatitis; HBV; Chronic Hepatitis B; Hepatitis B Virus
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; 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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes