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

Virion Therapeutics

Status and phase: Active, not recruiting; Phase 1

Conditions: Chronic Hepatitis B

Treatments: Biological: VRON-0200-AdC6; Drug: VIR-2218; Biological: VRON-0200-AdC7; Drug: VIR-3434

Study type: Interventional

Funder types: Industry

Identifiers

NCT06070051

21-0200-101

Details and patient eligibility

About

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.

Enrollment: 56 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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56 participants in 6 patient groups

Cohort 1a: Low Dose VRON-0200-AdC7 Prime, VRON-0200-AdC6 Boost

Experimental group

Description:

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.

Treatment:

Biological: VRON-0200-AdC7

Biological: VRON-0200-AdC6

Cohort 1b: Low Dose VRON-0200-AdC6 Prime, No Boost

Experimental group

Description:

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.

Treatment:

Biological: VRON-0200-AdC6

Cohort 2a: High Dose VRON-0200-AdC7 Prime, VRON-0200-AdC6 Boost

Experimental group

Description:

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.

Treatment:

Biological: VRON-0200-AdC7

Biological: VRON-0200-AdC6

Cohort 2b: High Dose VRON-0200-AdC6 Prime, No Boost

Experimental group

Description:

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.

Treatment:

Biological: VRON-0200-AdC6

Cohort 3a: High Dose VRON-0200-AdC7 Prime, 6 Doses VIR-2218 + VIR-3434, VRON-0200-AdC6 Boost

Experimental group

Description:

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.

Treatment:

Drug: VIR-3434

Biological: VRON-0200-AdC7

Drug: VIR-2218

Biological: VRON-0200-AdC6

Cohort 3b: High Dose VRON-0200-AdC7 Prime, 6 Doses VIR-2218 + VIR-3434, No Boost

Experimental group

Description:

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.

Treatment:

Drug: VIR-3434

Biological: VRON-0200-AdC7

Drug: VIR-2218