A Phase 1b Multi-Center, Open-Label, Dose-Escalation, Prime And Boost Vaccination Evaluation of VRON-0200 Using Two Chimpanzee Adenoviral Vectors in Adult Participants With Chronic HBV Infection Who Are Currently Receiving HBV Nucleos(t)Ide Reverse Transcriptase Inhibitors
Overview
- Phase
- Phase 1
- Intervention
- VRON-0200-AdC6
- Conditions
- Chronic Hepatitis B
- Sponsor
- Virion Therapeutics
- Enrollment
- 48
- Locations
- 3
- Primary Endpoint
- Treatment Emergent Adverse Events
- Status
- Active, not recruiting
- Last Updated
- 11 months ago
Overview
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.
All vaccine doses will be administered by intramuscular (IM) injection.
All study participants will be followed for a total of 1 year post-prime vaccination.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented chronic HBV infection (eg, HBsAg+ ≥ 6 months with detectable HBsAg at screening)
- •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
- •Virally suppressed for \> 12 months (HBV DNA \< 40 IU/mL)
- •No clinical diagnosis of advanced liver fibrosis and/or cirrhosis
Exclusion Criteria
- •History of hepatic decompensation, advanced fibrosis, or liver transplantation
- •History of hepatocellular carcinoma
- •History of risk factors for thrombosis and thrombocytopenia
- •Documented hepatitis A, hepatitis C, hepatitis D, hepatitis E, or HIV (or history of prior active disease)
- •Pregnant, nursing, or planning a pregnancy during the trial
Arms & Interventions
Cohort 1a: Low Dose VRON-0200-AdC7 Prime, VRON-0200-AdC6 Boost
Participants assigned to Cohort 1a will receive a low dose prime vaccination of AdC7 vector on Day 1. They will receive a low dose boost vaccination of vector AdC6 on Day 91.
Intervention: VRON-0200-AdC6
Cohort 1a: Low Dose VRON-0200-AdC7 Prime, VRON-0200-AdC6 Boost
Participants assigned to Cohort 1a will receive a low dose prime vaccination of AdC7 vector on Day 1. They will receive a low dose boost vaccination of vector AdC6 on Day 91.
Intervention: VRON-0200-AdC7
Cohort 1b: Low Dose VRON-0200-AdC6 Prime, No Boost
Participants assigned to Cohort 1b will receive a low dose prime vaccination of AdC6 vector on Day 1. They will not receive a booster vaccination.
Intervention: VRON-0200-AdC6
Cohort 2a: High Dose VRON-0200-AdC7 Prime, VRON-0200-AdC6 Boost
Participants assigned to Cohort 2a will receive a high dose prime vaccination of AdC7 vector on Day 1. They will receive a high dose boost vaccination of AdC6 vector on Day 91.
Intervention: VRON-0200-AdC6
Cohort 2a: High Dose VRON-0200-AdC7 Prime, VRON-0200-AdC6 Boost
Participants assigned to Cohort 2a will receive a high dose prime vaccination of AdC7 vector on Day 1. They will receive a high dose boost vaccination of AdC6 vector on Day 91.
Intervention: VRON-0200-AdC7
Cohort 2b: High Dose VRON-0200-AdC6 Prime, No Boost
Participants assigned to Cohort 2b will receive a high dose prime vaccination of AdC6 vector on Day 1. They will not receive a booster vaccination.
Intervention: VRON-0200-AdC6
Cohort 3a: High Dose VRON-0200-AdC7 Prime, 6 Doses VIR-2218 + VIR-3434, VRON-0200-AdC6 Boost
Participants assigned to Cohort 3a will receive a high dose prime vaccination of AdC7 vector on Day 1. They will receive VIR-2218 and VIR-3434 on Days 28, 56, 84, 112, 140, and 168. They will receive a high dose boost vaccination of AdC6 vector on Day 91.
Intervention: VRON-0200-AdC6
Cohort 3a: High Dose VRON-0200-AdC7 Prime, 6 Doses VIR-2218 + VIR-3434, VRON-0200-AdC6 Boost
Participants assigned to Cohort 3a will receive a high dose prime vaccination of AdC7 vector on Day 1. They will receive VIR-2218 and VIR-3434 on Days 28, 56, 84, 112, 140, and 168. They will receive a high dose boost vaccination of AdC6 vector on Day 91.
Intervention: VRON-0200-AdC7
Cohort 3a: High Dose VRON-0200-AdC7 Prime, 6 Doses VIR-2218 + VIR-3434, VRON-0200-AdC6 Boost
Participants assigned to Cohort 3a will receive a high dose prime vaccination of AdC7 vector on Day 1. They will receive VIR-2218 and VIR-3434 on Days 28, 56, 84, 112, 140, and 168. They will receive a high dose boost vaccination of AdC6 vector on Day 91.
Intervention: VIR-2218
Cohort 3a: High Dose VRON-0200-AdC7 Prime, 6 Doses VIR-2218 + VIR-3434, VRON-0200-AdC6 Boost
Participants assigned to Cohort 3a will receive a high dose prime vaccination of AdC7 vector on Day 1. They will receive VIR-2218 and VIR-3434 on Days 28, 56, 84, 112, 140, and 168. They will receive a high dose boost vaccination of AdC6 vector on Day 91.
Intervention: VIR-3434
Cohort 3b: High Dose VRON-0200-AdC7 Prime, 6 Doses VIR-2218 + VIR-3434, No Boost
Participants assigned to Cohort 3a will receive a high dose prime vaccination of AdC7 vector on Day 1. They will receive VIR-2218 and VIR-3434 on Days 28, 56, 84, 112, 140, and 168. They will not receive a boost vaccination.
Intervention: VRON-0200-AdC7
Cohort 3b: High Dose VRON-0200-AdC7 Prime, 6 Doses VIR-2218 + VIR-3434, No Boost
Participants assigned to Cohort 3a will receive a high dose prime vaccination of AdC7 vector on Day 1. They will receive VIR-2218 and VIR-3434 on Days 28, 56, 84, 112, 140, and 168. They will not receive a boost vaccination.
Intervention: VIR-2218
Cohort 3b: High Dose VRON-0200-AdC7 Prime, 6 Doses VIR-2218 + VIR-3434, No Boost
Participants assigned to Cohort 3a will receive a high dose prime vaccination of AdC7 vector on Day 1. They will receive VIR-2218 and VIR-3434 on Days 28, 56, 84, 112, 140, and 168. They will not receive a boost vaccination.
Intervention: VIR-3434
Outcomes
Primary Outcomes
Treatment Emergent Adverse Events
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 6 months
Number and percent of participants with serious adverse events within 6 months after the last dose by cohort.
Medically Attended Adverse Events
Time Frame: 6 months
Number and percent of participants with medically attended adverse events within 6 months after the last dose by cohort.
Secondary Outcomes
- Adverse Events(360 days)
- T Cell Frequencies(360 days)