Clinical trial NCT06070051: Dose-Escalation Prime/Boost Therapeutic Vaccination Study Of 2 Chimp Adenoviral Vectors in Adults With Chronic HBV On Nucleos(t)Ide Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Chronic Hepatitis B
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
Lead sponsor: Virion Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Vir Biotechnology, Inc.
First posted: 2023-10-06
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Treatment Emergent Adverse Events
timeFrame: 28 days
measure: Grade 3 Adverse Events
timeFrame: 28 days
measure: Clinically Significant Changes in Lab Values
timeFrame: 28 days
measure: Serious Adverse Events
timeFrame: 6 months
measure: Medically Attended Adverse Events
timeFrame: 6 months
Secondary outcomes:
measure: Adverse Events
timeFrame: 360 days
measure: T Cell Frequencies
timeFrame: 360 days
Other outcomes:
measure: Hepatitis B Virus DNA
timeFrame: 360 days
measure: Hepatitis B Virus Pregenomic RNA
timeFrame: 360 days
measure: Hepatitis B Surface Antigen
timeFrame: 360 days
Locations:
city: Hong Kong
country: Hong Kong
facility: Chinese University of Hong Kong
city: Auckland
country: New Zealand
facility: Aotearoa Clinical Trials, Middlemore Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
affiliation: Virion Therapeutics
name: Sue Currie, PhD
role: STUDY_DIRECTOR
References: