Dose-Escalation Prime/Boost Therapeutic Vaccination Study Of 2 Chimp Adenoviral Vectors in Adults With Chronic HBV On Nucleos(t)Ide Therapy

Dose-Escalation Prime/Boost Therapeutic Vaccination Study Of 2 Chimp Adenoviral Vectors in Adults With Chronic HBV On Nucleos(t)Ide Therapy

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

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.

Hep B, Chronic Hep B, HBV, Hepatitis B Virus, Chronic Hepatitis B Virus, CHB, VRON-0200, Virion, therapeutic vaccine

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.

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.

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.

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.

Number and percent of participants with 1 or more treatment-emergent adverse events within 28 days after each therapeutic vaccine dose by cohort.

Number and percent of participants with Grade 3 or higher local and/or systemic reactions within 28 days after each therapeutic vaccine dose by cohort.

Number and percent of participants with clinically significant changes from pre-vaccination laboratory values within 28 days after each therapeutic vaccine dose by cohort.

Number and percent of participants with serious adverse events within 6 months after each therapeutic vaccine dose by cohort.

Number and percent of participants with medically attended adverse events within 6 months after each therapeutic vaccine dose by cohort.

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