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

Study Overview
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Brief Summary
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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).

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

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Biological: VIR-3434
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIR-3434<br> | Biological: VIR-3434<br>* VIR-3434 given by subcutaneous injection or intravenous infusion.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Sterile normal saline (0.9% NaCl) given by subcutaneous injection or intravenous infusion.<br>|

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis