Dose-Escalation Prime/Boost Therapeutic Vaccination Study Of 2 Chimp Adenoviral Vectors in Adults With Chronic HBV On Nucleos(t)Ide Therapy
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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. |
Biological: VRON-0200-AdC6
VRON-0200 chimpanzee adenovirus serotype 6 vaccine vector
Biological: VRON-0200-AdC7
VRON-0200 chimpanzee adenovirus serotype 7 vaccine vector
|
Experimental: 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. |
Biological: VRON-0200-AdC6
VRON-0200 chimpanzee adenovirus serotype 6 vaccine vector
|
Experimental: 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. |
Biological: VRON-0200-AdC6
VRON-0200 chimpanzee adenovirus serotype 6 vaccine vector
Biological: VRON-0200-AdC7
VRON-0200 chimpanzee adenovirus serotype 7 vaccine vector
|
Experimental: 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. |
Biological: VRON-0200-AdC6
VRON-0200 chimpanzee adenovirus serotype 6 vaccine vector
|
Outcome Measures
Primary Outcome Measures
- Treatment Emergent Adverse Events [28 days]
Number and percent of participants with 1 or more treatment-emergent adverse events within 28 days after each therapeutic vaccine 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 each therapeutic vaccine 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 each therapeutic vaccine dose by cohort.
- Serious Adverse Events [6 months]
Number and percent of participants with serious adverse events within 6 months after each therapeutic vaccine dose by cohort.
- Medically Attended Adverse Events [6 months]
Number and percent of participants with medically attended adverse events within 6 months after each therapeutic vaccine dose by cohort.
Secondary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Chinese University of Hong Kong | Hong Kong | Hong Kong | ||
2 | Auckland City Hospital | Auckland | New Zealand |
Sponsors and Collaborators
- Virion Therapeutics
Investigators
- Study Director: Sue Currie, PhD, Virion Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 21-0200-101