Study of VIR-3434 in Healthy Volunteers and Patients With Chronic Hepatitis B Virus Infection
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
VIR-3434
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis
Eligibility Criteria
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
Sites / Locations
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
VIR-3434
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Incidence of treatment-emergent adverse events (TEAEs)
Clinical assessment of changes in physical examinations
Clinical assessment and quantification of changes in vital signs: blood pressure
Clinical assessment and quantification of changes in vital signs: pulse rate
Clinical assessment and quantification of changes in vital signs: temperature
Clinical assessment and quantification of changes in vital signs: respiratory rate
Proportion of subjects with abnormalities in ECGs
Clinical assessment and quantification of changes in liver function tests
Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin
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
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
Clinical assessment and quantification of changes in coagulation parameters
INR and prothrombin time
Clinical assessment and quantification of changes in urinalysis parameters
Bilirubin, glucose, ketones, leukocytes, nitrite, pH, proteins, red blood cells, specific gravity, and urobilinogen
Clinical assessment and quantification of changes in complement
C3 and C4
Clinical assessment of changes in local tolerability using a numeric scoring tool that is based on FDA and DAIDs injection site reaction grading scales
Secondary Outcome Measures
Cmax
Clast
Tmax
Tlast
AUCinf
AUClast
%AUCexp
t1/2
λz
Vz (IV only)
CL (IV only)
Vz/F (SC only)
CL/F (SC only)
Incidence of ADA to VIR-3434
Titers of ADA to VIR-3434
Maximum reduction of serum HBsAg from baseline (Day 1 predose)
Part D only: maximum change of HBV DNA from baseline (Day 1 predose)
Full Information
NCT ID
NCT04423393
First Posted
May 25, 2020
Last Updated
December 16, 2022
Sponsor
Vir Biotechnology, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04423393
Brief Title
Study of VIR-3434 in Healthy Volunteers and Patients With Chronic Hepatitis B Virus Infection
Official Title
A Phase 1, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-3434
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
May 26, 2020 (Actual)
Primary Completion Date
October 24, 2022 (Actual)
Study Completion Date
November 25, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vir Biotechnology, Inc.
4. Oversight
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
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
113 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VIR-3434
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
VIR-3434
Intervention Description
VIR-3434 given by subcutaneous injection or intravenous infusion.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Sterile normal saline (0.9% NaCl) given by subcutaneous injection or intravenous infusion.
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events (TEAEs)
Time Frame
Up to 280 days post-dose
Title
Clinical assessment of changes in physical examinations
Time Frame
Up to 280 days post-dose
Title
Clinical assessment and quantification of changes in vital signs: blood pressure
Time Frame
Up to 280 days post-dose
Title
Clinical assessment and quantification of changes in vital signs: pulse rate
Time Frame
Up to 280 days post-dose
Title
Clinical assessment and quantification of changes in vital signs: temperature
Time Frame
Up to 280 days post-dose
Title
Clinical assessment and quantification of changes in vital signs: respiratory rate
Time Frame
Up to 280 days post-dose
Title
Proportion of subjects with abnormalities in ECGs
Time Frame
Up to 280 days post-dose
Title
Clinical assessment and quantification of changes in liver function tests
Description
Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin
Time Frame
Up to 280 days post-dose
Title
Clinical assessment and quantification of changes in serum chemistry parameters
Description
Albumin, blood urea nitrogen, calcium, carbon dioxide/bicarbonate, chloride, creatine kinase, creatinine, creatinine clearance, gamma glutamyl transferase, glucose, lactate dehydrogenase, potassium, and sodium
Time Frame
Up to 280 days post-dose
Title
Clinical assessment and quantification of changes in hematology parameters
Description
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
Time Frame
Up to 280 days post-dose
Title
Clinical assessment and quantification of changes in coagulation parameters
Description
INR and prothrombin time
Time Frame
Up to 280 days post-dose
Title
Clinical assessment and quantification of changes in urinalysis parameters
Description
Bilirubin, glucose, ketones, leukocytes, nitrite, pH, proteins, red blood cells, specific gravity, and urobilinogen
Time Frame
Up to 280 days post-dose
Title
Clinical assessment and quantification of changes in complement
Description
C3 and C4
Time Frame
Up to 280 days post-dose
Title
Clinical assessment of changes in local tolerability using a numeric scoring tool that is based on FDA and DAIDs injection site reaction grading scales
Time Frame
Up to 280 days post-dose
Secondary Outcome Measure Information:
Title
Cmax
Time Frame
Up to 280 days post-dose
Title
Clast
Time Frame
Up to 280 days post-dose
Title
Tmax
Time Frame
Up to 280 days post-dose
Title
Tlast
Time Frame
Up to 280 days post-dose
Title
AUCinf
Time Frame
Up to 280 days post-dose
Title
AUClast
Time Frame
Up to 280 days post-dose
Title
%AUCexp
Time Frame
Up to 280 days post-dose
Title
t1/2
Time Frame
Up to 280 days post-dose
Title
λz
Time Frame
Up to 280 days post-dose
Title
Vz (IV only)
Time Frame
Up to 280 days post-dose
Title
CL (IV only)
Time Frame
Up to 280 days post-dose
Title
Vz/F (SC only)
Time Frame
Up to 280 days post-dose
Title
CL/F (SC only)
Time Frame
Up to 280 days post-dose
Title
Incidence of ADA to VIR-3434
Time Frame
Up to 280 days post-dose
Title
Titers of ADA to VIR-3434
Time Frame
Up to 280 days post-dose
Title
Maximum reduction of serum HBsAg from baseline (Day 1 predose)
Time Frame
Up to 280 days post-dose
Title
Part D only: maximum change of HBV DNA from baseline (Day 1 predose)
Time Frame
Up to 280 days post-dose
Other Pre-specified Outcome Measures:
Title
Assessment of mean changes in HBV RNA levels
Time Frame
Up to 280 days post-dose
Title
Assessment of mean changes in HBcrAg levels
Time Frame
Up to 280 days post-dose
Title
Evaluation of host immune responses in peripheral blood, including analysis of circulating biomarkers and cellular immunity
Time Frame
Up to 280 days post-dose
Title
Analysis and evaluation of host gene expression by RNA-sequencing
Time Frame
Up to 280 days post-dose
Title
Fc gamma receptor (FcγR) polymorphisms as determined by genotyping
Time Frame
Day 1
Title
IgG allotypes as determined by genotyping
Time Frame
Day 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
Investigative Site
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Investigative Site
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Investigative Site
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Investigative Site
City
Busan
ZIP/Postal Code
47392
Country
Korea, Republic of
Facility Name
Investigative Site
City
Busan
ZIP/Postal Code
49241
Country
Korea, Republic of
Facility Name
Investigative Site
City
Seoul
ZIP/Postal Code
02841
Country
Korea, Republic of
Facility Name
Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Investigative Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Investigative Site
City
Seoul
ZIP/Postal Code
06273
Country
Korea, Republic of
Facility Name
Investigative Site
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Facility Name
Investigative Site
City
Havelock North
ZIP/Postal Code
4130
Country
New Zealand
Facility Name
Investigative Site
City
Tauranga
ZIP/Postal Code
3110
Country
New Zealand
Facility Name
Investigative Site
City
Wellington
ZIP/Postal Code
6021
Country
New Zealand
Facility Name
Investigative Site
City
Bucharest
Country
Romania
Facility Name
Investigative Site
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Investigative Site
City
Singapore
ZIP/Postal Code
529889
Country
Singapore
Facility Name
Investigative Site
City
Birmingham
ZIP/Postal Code
B15 2GW
Country
United Kingdom
Facility Name
Investigative Site
City
London
ZIP/Postal Code
E1 1FR
Country
United Kingdom
Facility Name
Investigative Site
City
Manchester
ZIP/Postal Code
M8 5RB
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of VIR-3434 in Healthy Volunteers and Patients With Chronic Hepatitis B Virus Infection
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