NCT04778904

First-In-Human Study of ChAdOx1-HBV & MVA-HBV Vaccines (VTP-300) for Chronic HBV

A Phase 1b/2a, Open-Label Study to Evaluate the Safety, Tolerability and Immunogenicity of VTP-300 With or Without Nivolumab in Participants With Chronic Hepatitis B Infection

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 55 (actual)
• Sponsor: Barinthus Biotherapeutics · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label study to determine the safety, tolerability and immunogenicity of ChAdOx1-HBV and MVA-HBV vaccines, with or without nivolumab, in patients with chronic HBV who are virally suppressed with oral anti-viral therapies.

Detailed description

This is a multi-centre study conducted in 52 participants, who will each be administered 2 vaccine injections (IM) on Day 0 and Day 28 as follows: Group 1: MVA-HBV + MVA-HBV (now closed) Group 2: ChAdOx1-HBV + MVA-HBV Group 3: ChAdOx1-HBV + MVA-HBV + nivolumab (IV infusion) Group 4: ChAdOx1-HBV + nivolumab + MVA-HBV + nivolumab (now closed) Participants are randomised to treatment as the groups are initiated with a 1:1:1:1 allocation. Version 6.0 of the study protocol has closed Groups 1 and 4 to further randomisation; recruitment will now be in a 1:1 ratio between Groups 2 and 3 only. A sentinel participant is dosed in Group 1, with further participants in Group 1 only being dosed at least 48h later. Group 2 is initiated following a Day 7 safety assessment of the first 6 participants in Group 1. Groups 3 and 4 are initiated following a Day 7 safety assessment of the first 6 participants in Group 2. The primary objective of the study is to determine the safety and reactogenicity of the treatment regimens; this will be assessed by analysis of the incidence and severity of (serious) adverse events and any changes in laboratory values and vital signs. The secondary objectives of the study are the determination of the immunogenicity of the ChAdOx1-HBV and MVA-HBV vaccines and the impact of PD-blockade, as well as the effect on HBV markers; these are assessed by measurements of the magnitude and avidity of HBV-specific CD4+ and CD8+ T cells and the magnitude of HBV markers. Following first vaccination, participants remain in the study for 9 months and attend clinic visits for vaccination and assessments on Days 0, 7, 28, 35 and Months, 3, 6 and 9.

Conditions

• Hepatitis B

Interventions

Type	Name	Description
BIOLOGICAL	ChAdOx1-HBV	Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus vaccine
BIOLOGICAL	MVA-HBV	Modified Vaccinia Ankara-vectored Hepatitis B virus vaccine
BIOLOGICAL	Nivolumab	Human immunoglobulin G4 monoclonal antibody

Timeline

• Start date: 2020-12-22
• Primary completion: 2023-02-24
• Completion: 2023-02-24
• First posted: 2021-03-03
• Last updated: 2024-08-13
• Results posted: 2024-08-13

Locations

12 sites across 3 countries: South Korea, Taiwan, United Kingdom