Chronic Hepatitis B
Conditions
Keywords
Hep B, Chronic Hep B, HBV, Hepatitis B Virus, Chronic Hepatitis B Virus, CHB, VRON-0200, Virion, therapeutic vaccine, VIR-2218, VIR-3434, Functional cure, Hepatitis B, Chronic Hepatitis B
Brief summary
This Phase 1b clinical study is a multi-center, open-label, dose escalation, prime only, and prime plus boost therapeutic vaccination study of 2 distinct chimpanzee adenoviral vectors (AdC6 and AdC7), containing parts of hepatitis B virus (HBV) core and polymerase antigens fused within glycoprotein D in a cohort of chronic hepatitis B (CHB)-infected adult participants who are currently receiving entecavir, tenofovir (tenofovir alafenamide fumarate or tenofovir disoproxil fumarate), or lamivudine, with documented HBV viral load suppression for at least 12 months. Approximately 24 participants will be enrolled in Group 1 and randomized to Cohort 1a or Cohort 1b. Those assigned to Cohort 1a will receive a low dose prime therapeutic vaccination of vector AdC7 on Day 1, followed by a booster vaccination on Day 91 using vector AdC6. Those assigned to Cohort 1b will receive a low dose prime therapeutic vaccination of vector AdC6 on Day 1, and will not receive a booster vaccination. Group 2 will then enroll approximately 24 participants randomized to Cohort 2a or Cohort 2b. Those assigned to Cohort 2a will receive a high dose prime therapeutic vaccination of vector AdC7 on Day 1, followed by a booster vaccination on Day 91 using vector AdC6. Those assigned to Cohort 2b will receive a high dose prime therapeutic vaccination of vector AdC6 on Day 1, and will not receive a booster vaccination. Group 3 will enroll approximately 8 participants randomized into Cohort 3a or Cohort 3b. Cohort 3a will receive the high dose prime VRON-0200 vaccination of vector AdC7 on Day 1, followed by doses of VIR-2218 plus VIR-3434 on Days 28, 56, 84, 112, 140 and 168, and then a booster using a high dose VRON-0200 vaccination of vector AdC6 on Day 196. Cohort 3b will receive the same high dose prime VRON-0200 vaccination of vector AdC7 followed by 6 doses of VIR-2218 plus VIR-3434 at the same timepoints as Cohort 3a, but will not receive the booster dose on Day 196. VRON-0200 vaccine doses will be administered by intramuscular (IM) injection. VIR-2218 and VIR-3434 will be administered subcutaneously. All study participants will be followed for a total of 1 year post-prime vaccination.
Interventions
Sponsors
Vir Biotechnology, Inc.
Virion Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Documented chronic HBV infection (eg, HBsAg+ ≥ 6 months with detectable HBsAg at screening) 2. Receipt of either entecavir, tenofovir (tenofovir alafenamide fumarate or tenofovir disoproxil fumarate), or lamivudine for at least 12 months before screening with no reported antiviral resistance during this time; still on treatment at screening and expected to stay on therapy during the study period 3. Virally suppressed for \> 12 months (HBV DNA \< 40 IU/mL) 4. No clinical diagnosis of advanced liver fibrosis and/or cirrhosis
Exclusion criteria
1. History of hepatic decompensation, advanced fibrosis, or liver transplantation 2. History of hepatocellular carcinoma 3. History of risk factors for thrombosis and thrombocytopenia 4. Documented hepatitis A, hepatitis C, hepatitis D, hepatitis E, or HIV (or history of prior active disease) 5. Pregnant, nursing, or planning a pregnancy during the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Medically Attended Adverse Events | 6 months | Number and percent of participants with medically attended adverse events within 6 months after the last dose by cohort. |
| Treatment Emergent Adverse Events | 28 days | Number and percent of participants with 1 or more treatment-emergent adverse events within 28 days after the last dose by cohort. |
| Grade 3 Adverse Events | 28 days | Number and percent of participants with Grade 3 or higher local and/or systemic reactions within 28 days after the last dose by cohort. |
| Clinically Significant Changes in Lab Values | 28 days | Number and percent of participants with clinically significant changes from pre-vaccination laboratory values within 28 days after the last dose by cohort. |
| Serious Adverse Events | 6 months | Number and percent of participants with serious adverse events within 6 months after the last dose by cohort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 360 days | Number and percentage of adverse events for all participants through Day 360. |
| T Cell Frequencies | 360 days | Change from baseline in vaccine-induced CD8+ T cell frequencies in the blood. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hepatitis B Virus DNA | 360 days | Quantitative changes from baseline over time in HBV DNA |
| Hepatitis B Virus Pregenomic RNA | 360 days | Quantitative changes from baseline over time in HBV pgRNA |
| Hepatitis B Surface Antigen | 360 days | Quantitative changes from baseline over time in HBsAg |
Countries
Hong Kong, New Zealand
Outcome results
None listed