First in Human Study of ChAdOx1-HBV in Healthy Participants and Participants With Chronic hepB Infection

NCT04297917 | Completed Phase 1 Results DMC

• 1 other identifier: HBV001
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase 1, first in human study of ChAdOx1-HBV. The study will be conducted in 40 healthy participants and 12 participants with CHB and virally suppressed with oral antiviral medication. This will be an open-label, non randomised dose escalation study comparing the safety, tolerability and immunogenicity of 2 different doses of ChAdOx1 HBV vaccine. T cell responses in healthy participants who have received a prior two-dose series of AZD1222 will be compared with those who have received either the Pfizer COVID 19 vaccine or the Moderna mRNA COVID 19 vaccine.

Conditions

Hepatitis B; Healthy

Outcome Measures

Primary Outcomes (5)

• Incidence of Safety and Reactogenicity Events: Adverse Events

  Adverse events and/or adverse events leading to study discontinuation. Percentages are based on the number of participants in the Safety Analysis Set.

  Recorded in the eCRF from the date the informed consent is signed, at all clinic visits (D0, D1, D7, D14, D28, D56, D84) to cover the period since the previous visit and during the visit and up to 168 days post-vaccination (6 months)

• Incidence of Safety and Reactogenicity Events: Serious Adverse Events

  Serious adverse events related to the study vaccine. Percentages are based on the number of participants in the Safety Analysis Set.

  From day 0 to up to 6 months

• Incidence of Safety and Reactogenicity Events: Grade ≥3 Local Reactions

  Local reactions were collected by the investigator pre and post vaccination on Day 0. In addition, local reactions were captured in the participant diary card on Days 1, 2 and 3. The number and percentage of participants who experienced any symptom are summarised.

  From day 0 to day 3

• Incidence of Safety and Reactogenicity Events: Grade ≥3 Systemic Reactions

  Systemic reactions were collected by the investigator pre and post vaccination on Day 0 and captured in the participant diary card on Days 1, 2 and 3. The number and percentage of participants who experienced any symptom are summarised.

  From day 0 to day 3

• Effect of Prior AZD1222 on the CD8+ T Cell Magnitude and Phenotype as Measured by Multiparameter Flow Cytometry

  Intracellular cytokine staining analysis to measure IFNγ, produced by HBV antigen or hexon-specific CD8+ T cells in PBMC across study timepoints

  Baseline, Day 14, 28, 56, 84

Secondary Outcomes (11)

• Reduction in HBsAg Titre Post-vaccination in CHB Participants

  Baseline, Day 28, 56, 84 and 168

• Loss of Both HBeAg and HBsAg

  Baseline and Day 168

• Proportion of CHB Participants With HBeAg and HBsAg Seroconversion

  Baseline, Day 28, 56, 84 and 168

• Reduction of Hepatitis B DNA Levels in CHB Participants

  Baseline, Day 28, 56, 84 and 168

• Percentage of CD4+ and CD8+ Expressing IFNγ at Baseline and Days 14, 28, 56, and 84 After Vaccination

  Baseline, 14, 28, 56, and 84

Study Arms (6)

Healthy Volunteers with low dose vaccination

EXPERIMENTAL

5 Healthy Volunteers receiving low dose vaccination

Biological: ChAdOx1-HBV

Healthy Volunteers with high dose vaccination

EXPERIMENTAL

5 Healthy Volunteers receiving high dose vaccination

Biological: ChAdOx1-HBV

Chronic Hepatitis B participants with low dose vaccination

EXPERIMENTAL

6 participants with Chronic Hepatitis B infection receiving low dose vaccination

Biological: ChAdOx1-HBV

Chronic Hepatitis B participants with high dose vaccination

EXPERIMENTAL

5 participants with Chronic Hepatitis B infection receiving high dose vaccination

Biological: ChAdOx1-HBV

Healthy Volunteers who have had COVID-19 AZD1222 vaccine

EXPERIMENTAL

15 participants who have had 2 doses of COVID-19 AZD1222 vaccine receiving high dose vaccination.

Biological: ChAdOx1-HBV

Healthy Volunteers who have had Pfizer/Moderna mRNA COVID 19 vaccine

EXPERIMENTAL

11 participants who have had 2 doses of either Pfizer/Moderna mRNA COVID 19 vaccine receiving high dose vaccination

Biological: ChAdOx1-HBV

Interventions

ChAdOx1-HBV BIOLOGICAL

chimpanzee adenovirus-vectored hepatitis B virus vaccine

Chronic Hepatitis B participants with high dose vaccination; Chronic Hepatitis B participants with low dose vaccination; Healthy Volunteers who have had COVID-19 AZD1222 vaccine; Healthy Volunteers who have had Pfizer/Moderna mRNA COVID 19 vaccine; Healthy Volunteers with high dose vaccination; Healthy Volunteers with low dose vaccination

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males or females aged ≥18 to ≤65 years at screening
• Body Mass Index ≤30 kg/m2
• Able to provide informed consent indicating they understand the purpose of, and procedures required, for the study and are willing to participate
• If female, willing not to become pregnant up to 8 weeks after last dose of study vaccine, not breast feeding
• If female: Not pregnant, and one of the following:
• Of non-childbearing potential (i.e. women who have had a hysterectomy or tubal ligation or are post menopausal, as defined by no menses in ≥1 year)
• Sexual abstinence, only if the participant refrains from heterosexual intercourse during the entire study period and it is the usual lifestyle of the participant
• Of childbearing potential but agrees to practice highly effective contraception for 4 weeks prior to study vaccine and 8 weeks after study vaccine. Highly effective methods of contraception include one or more of the following:
• Male partner who is sterile (medically effective vasectomy) prior to the female participant's entry into the study and is the sole sexual partner for the female participant, Hormonal (oral, intravaginal, transdermal, implantable or injectable), An intrauterine hormone releasing system, An intrauterine device and Bilateral tubal occlusion
• Healthy participants (cohorts 1 and 2):
• Considered to be healthy with no current conditions that may significantly impair participant safety or influence study results, in the opinion of the Investigator
• Participants with well controlled CHB (cohorts 3 and 4):
• Documented evidence of chronic HBV infection (e.g. HBsAg positive ≥6 months with detectable HBsAg levels at screening)
• Receipt of only either entecavir or tenofovir for at least 12 months before screening
• Virally suppressed (HBV DNA \<40 IU/mL for ≥6 months)

You may not qualify if:

• Presence of any significant acute or chronic, uncontrolled medical/ psychiatric illness
• Hepatitis C virus antibody positive.
• Human immunodeficiency virus antibody positive
• History or evidence of autoimmune disease or known immunodeficiency of any cause
• Prolonged therapy with immunomodulators (e.g. corticosteroids) or biologics (e.g. monoclonal antibodies, interferon) within 3 months of screening
• Receipt of immunoglobulin or other blood products within 3 months prior to screening
• Receipt of any investigational drug or vaccine within 3 months prior to screening
• Cohorts 1-4: Receipt of any adenoviral vaccine within 3 months prior to administration of ChAdOx1-HBV on Day 0, or plan to receive an adenoviral-based vaccine within 3 months after Day 0
• Receipt of any live vaccines within 30 days prior to screening
• Receipt of any inactivated vaccines within 14 days prior to screening
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
• Any history of anaphylaxis in reaction to vaccination
• Malignancy within 5 years prior to screening with the exception of specific cancers that are cured by surgical resection (e.g. except basal cell skin carcinoma of the skin and cervical carcinoma). Participants under evaluation for possible malignancy are not eligible
• Current alcohol or substance abuse judged by the Investigator to potentially interfere with participant safety and compliance
• Significant cardiac disease or unstable uncontrolled cardiac disease

Sponsors & Collaborators

• Barinthus Biotherapeutics: lead

Study Sites (4)

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Oxford University Hospitals Nhs Foundation Trust

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)

Headington, Oxford, OX3 7LE, United Kingdom

Location

Medicines Evaluations Unit

Manchester, M23 9QZ, United Kingdom

Location

Related Publications (1)

• Cargill T, Cicconi P, Brown A, Holland L, Karanth B, Rutkowski K, Ashwin E, Mehta R, Chinnakannan S, Sebastian S, Bussey L, Sorensen H, Klenerman P, Evans T, Barnes E. HBV001: Phase I study evaluating the safety and immunogenicity of the therapeutic vaccine ChAdOx1-HBV. JHEP Rep. 2023 Aug 18;5(11):100885. doi: 10.1016/j.jhepr.2023.100885. eCollection 2023 Nov.

  PMID: 37791379 DERIVED

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Limitations and Caveats

\[Not specified\]

Results Point of Contact

• Title: Tom Evan, MD
• Organization: Vaccitech Plc

enquiries@vaccitech.co.uk

+44 01865 591 445

Study Officials

• Eleanor Barnes, Prof

  University of Oxford

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The participants were recruited in 6 cohorts as follows - Cohort 1 - Healthy Volunteers - Low dose Vaccine - 5 participants Cohort 2 - Healthy Volunteers - High dose Vaccine - 5 participants Cohort 3 - Participants with Chronic Hepatitis B infection - Low dose - 6 participants Cohort 4 - Participants with Chronic Hepatitis B infection - High dose - 5 participants Cohort 5 - Healthy Volunteers who have completed 2 doses of COVID-19 AZD1222 vaccine Cohort 6 - Healthy Volunteers who have completed 2 doses of either Pfizer or Moderna mRNA COVID 19 vaccine

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 6, 2020
• Study Start: February 10, 2019
• Primary Completion: May 23, 2022
• Study Completion: June 26, 2022
• Last Updated: August 12, 2025
• Results First Posted: August 12, 2025

Record last verified: 2025-07

Locations

GB (4)