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

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06070051
• Other study ID #: 21-0200-101
• Status: Recruiting
• Phase: Phase 1
• Start date: September 26, 2023
• Est. completion date: January 23, 2025

Study information

• Verified date: October 2023
• Source: Virion Therapeutics
• Contact: Tony Baca, MBA
• Phone: 1-800-841-9303
• Email: tbaca[@]viriontx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: January 23, 2025
• Est. primary completion date: July 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Biological:
• VRON-0200-AdC6
VRON-0200 chimpanzee adenovirus serotype 6 vaccine vector
• VRON-0200-AdC7
VRON-0200 chimpanzee adenovirus serotype 7 vaccine vector

Locations

Country	Name	City	State
Hong Kong	Chinese University of Hong Kong	Hong Kong
New Zealand	Auckland City Hospital	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
Virion Therapeutics

Countries where clinical trial is conducted

Hong Kong,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hepatitis B Virus DNA	Quantitative changes from baseline over time in HBV DNA	360 days
Other	Hepatitis B Virus Pregenomic RNA	Quantitative changes from baseline over time in HBV pgRNA	360 days
Other	Hepatitis B Surface Antigen	Quantitative changes from baseline over time in HBsAg	360 days
Primary	Treatment Emergent Adverse Events	Number and percent of participants with 1 or more treatment-emergent adverse events within 28 days after each therapeutic vaccine dose by cohort.	28 days
Primary	Grade 3 Adverse Events	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.	28 days
Primary	Clinically Significant Changes in Lab Values	Number and percent of participants with clinically significant changes from pre-vaccination laboratory values within 28 days after each therapeutic vaccine dose by cohort.	28 days
Primary	Serious Adverse Events	Number and percent of participants with serious adverse events within 6 months after each therapeutic vaccine dose by cohort.	6 months
Primary	Medically Attended Adverse Events	Number and percent of participants with medically attended adverse events within 6 months after each therapeutic vaccine dose by cohort.	6 months
Secondary	Adverse Events	Number and percentage of adverse events for all participants through Day 360.	360 days
Secondary	T Cell Frequencies	Change from baseline in vaccine-induced CD8+ T cell frequencies in the blood.	360 days