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Chronic Hepatitis BPhase 2NCT05343481

Efficacy of VTP-300 in Chronic Hepatitis B Infection

A Phase 2 study testing ChAdOx1-HBV, MVA-HBV and Nivolumab in people with Chronic Hepatitis B, run by Barinthus Biotherapeutics at 18 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is an open-label study to determine the efficacy, safety, tolerability and immunogenicity of ChAdOx1-HBV and MVA-HBV, together VTP-300, in combination with low-dose nivolumab, in patients with chronic HBV who are virally suppressed with oral anti-viral therapies. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Chronic Hepatitis B
What is being tested?
ChAdOx1-HBV, MVA-HBV and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
121 participants
Where
18 sitesin 3 countries
Study dates
21 Sep 2022to 13 Jan 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult males or females aged ≥18 to ≤65 years at screening (according to country/local regulations)
  • BMI ≤35 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 the last dose of study vaccine and up to 5 months after the last dose of nivolumab
  • If female: Not pregnant or breast feeding and one of the following:
  • Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in ≥1 year and without an alternative medical cause)
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  • Of childbearing potential but agrees to practice highly effective contraception for 4 weeks prior to study vaccine and 8 weeks after VTP-300 and 5 months after the last dose of nivolumab. 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
  • Combined (oestrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal
  • Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable or implantable
  • An intrauterine device
  • Bilateral tubal occlusion
  • Abstinence from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
  • Documented evidence of CHB infection (e.g., HBsAg positive ≥6 months with detectable HBsAg levels at screening; both HBeAg+ and HBeAg- allowed)
  • Receipt of only either entecavir, tenofovir (tenofovir alafenamide fumarate or tenofovir disoproxil fumarate) or besifovir for at least 6 months before screening
  • HBV-DNA viral load ≤ 1,000 IU/mL
  • HBsAg levels > 10 and ≤ 4,000 IU/mL

Who cannot join

  • Presence of any significant acute or chronic, uncontrolled medical or psychiatric illness in the opinion of the investigator would affect the safety of the participant or the evaluation of the data or interfere with adherence to the study requirements
  • Medical history that is thought to increase the participant's risk of reaction to a vaccine, including but not limited to capillary leak syndrome; transverse myelitis, Guillain Barré syndrome, thrombosis with thrombocytopenia syndrome (also termed vaccine-induced thrombotic thrombocytopenia); heparin-induced thrombocytopenia HCV RNA positive
  • HIV antibody positive and active hepatitis C (antibody positive and then DNA positive)
  • Co-infection with hepatitis D virus (HDV)
  • Documented cirrhosis or advanced fibrosis indicated by a liver biopsy within 6 months prior to Day 0 (Metavir activity grade A4 and stage F4; Ishak stages 5 - 6).
  • In the absence of a documented liver biopsy, either 1 of the following (not both):
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  • Screening Fibroscan with a result >9 kilopascals (kPa) (or the equivalent) within ≤ 6 months of screening, OR
  • Both screening FibroTest >0.48 and aspartate aminotransferase (AST) to platelet ratio index (APRI) of >1.
  • ALT >3 x ULN, or INR >1.5 unless the participant was stable on an anticoagulant regimen affecting INR, albumin <3.2 g/dL, direct bilirubin >1.5 x ULN, platelet count <100,000/µL.
  • A history of liver decompensation (e.g., ascites, encephalopathy or variceal haemorrhage)
  • Prior hepatocellular carcinoma
  • Chronic liver disease of a non-HBV aetiology. (Note that Gilbert's syndrome, asymptomatic gallstones and non-alcoholic fatty liver not associated with steatohepatitis are not exclusions)
  • History or evidence of autoimmune disease or known immunodeficiency of any cause except history of autoimmune thyroiditis if the participant is stable on replacement therapy
  • Evidence of interstitial lung disease, active pneumonitis, myocarditis or a history of myocarditis
  • Prolonged therapy with immunomodulators (e.g., corticosteroids such as prednisone >10 mg/day) or biologics (e.g., monoclonal antibodies, IFN) within 3 months of Day 1. Inhaled, intra-articular, intra-bursal or topical corticosteroids are allowed. Physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is allowed.
  • Receipt of immunoglobulin or other blood products within 3 months prior to Day 1
  • Receipt of any investigational drug or vaccine within 3 months prior to Day 1
  • Receipt of any non-oral adenoviral-based vaccine within 3 months prior to administration of ChAdOx1-HBV on Day 1
  • Severe reaction to any vaccine, requiring medical attention
  • Receipt of any live vaccines within 30 days prior to Day 1
  • Receipt of any inactivated non-live vaccines (e.g., mRNA, inactivated vaccines, toxoid vaccines) within 14 days prior to Day 1
  • History of severe hypersensitivity or anaphylactic reactions likely to be exacerbated by any component of VTP-300 or nivolumab, including severe allergy to egg
  • Malignancy within 5 years prior to screening with the exception of basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Participants under evaluation for possible malignancy are not eligible
  • Current alcohol or substance abuse judged by the investigator to potentially interfere with participant safety or compliance
  • Any laboratory test which is abnormal, and which is deemed by the investigator to be clinically significant
  • Any other finding that, in the opinion of the investigator, deems the participant unsuitable for the study

Trial locations and contacts

18 sites in 3 countries.

18 sites in 3 countries

Taiwan8 sites
  • Chia-Yi Christian Hospital

    Chiayi City, Taiwan, 60002

  • Dalin Tzu Chi Hospital

    Chiayi City

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung, Taiwan, 807

  • Chang Gung Memorial Hospital Kaohsiung

    Kaohsiung City

  • China Medical University Hospital

    Taichung, Taiwan, 404332

  • National Cheng Kung University Hospital

    Tainan, Taiwan, 704

  • National Taiwan University Hospital

    Taipei

  • Linkou Chang Gung Memorial Hospital

    Taoyuan City, Taiwan, 333

Other trials in Taiwan

Thailand8 sites
  • Chulabhorn Hospital

    Bangkok, Thailand, 10210

  • King Chulalongkorn Memorial Hospital

    Bangkok, Thailand, 10330

  • HIV Netherlands-Australia-Thailand Research Collaboration

    Bangkok, Thailand

  • Hospital For Tropical Diseases

    Bangkok

  • Maharaj Nakorn Chiang Mai Hospital

    Chiang Mai, Thailand, 50200

  • Research Institute For Health Sciences

    Chiang Mai

  • Srinagarind Hospital

    Khon Kaen

  • Bamrasnaradura Infectious Diseases Institute

    Nonthaburi, Thailand, 11000

Other trials in Thailand

Hong Kong2 sites
  • Prince Of Wales Hospital

    Hong Kong

  • Queen Mary Hospital

    Hong Kong

Other trials in Hong Kong

About this study

Official title: A Phase 2b, Open-label Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity and Treatment Regimens of VTP-300 Combined With Low-dose Nivolumab in Chronic Hepatitis B Infection

This is an open-label study to determine the efficacy, safety, tolerability and immunogenicity of ChAdOx1-HBV and MVA-HBV, together VTP-300, in combination with low-dose nivolumab, in patients with chronic HBV who are virally suppressed with oral anti-viral therapies.

Read the detailed description

This is a multi-centre study conducted in 120 participants. All treatment groups will receive ChAdOx1-HBV on Day 1 and MVA-HBV on Day 29, and MVA boosts and nivolumab infusions as per treatment group as follows: Group 1: ChAdOx1-HBV, MVA-HBV and low dose nivolumab. Group 2: ChAdOx1-HBV, MVA HBV + low dose nivolumab, MVA HBV and low dose nivolumab. Group 3: ChAdOx1-HBV, MVA HBV, low dose nivolumab , MVA HBV. All participants return 7 days after each treatment (both immunotherapeutic and nivolumab infusion) visit to have chemistry and haematology safety laboratory studies obtained.

Participants are randomised to treatment in a 1:1:1 allocation. The primary objective of the study is to assess the efficacy of VTP-300 in combination with low-dose nivolumab in well-controlled CHB infection. The secondary 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. To assess the effect of VTP-300 in combination with low-dose nivolumab on the clearance of HBsAg and the impact of multiple booster doses of MVA-HBV and assess the appropriate timing of the use of low-dose nivolumab when used in combination with VTP-300.

Participants remain in the study for 12 months and attend clinic visits for treatment and assessments on Days 1, 8, 29, 36, 57, 85, 92, 113, 169, 252 and 336 (per Group allocation).

Being tested
ChAdOx1-HBV, MVA-HBV, Nivolumab
Keywords
HBV, Chronic Hep B
Medical subject headings
Hepatitis B, Chronic, Hepatitis B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ChAdOx1-HBVBiological

    Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus immunotherapeutic

  • MVA-HBVBiological

    Modified Vaccinia Ankara-vectored Hepatitis B virus immunotherapeutic

  • NivolumabBiological

    Also called Opdivo 10mg/ml concentrate for solution for infusion

    Human immunoglobulin G4 monoclonal antibody

Study groups in NCT05343481
Study groupRoleWhat they receive
Experimental: Group 1 ChAdOx1-HBV, MVA-HBV and nivolumabExperimentalDay 1: ChAdOx1-HBV 1 x 2.5 10^10 vp IM injection Day 29: MVA-HBV 1 x 10^8 pfu IM injection + nivolumab 0.3 mg/kg IV infusion
Receives: Biological: ChAdOx1-HBV; Biological: MVA-HBV; Biological: Nivolumab
Experimental: Group 2 ChAdOx1-HBV, MVA-HBV and nivolumab, MVA-HBV and nivolumabExperimentalDay 1: ChAdOx1-HBV 1 x 2.5 10^10 vp IM injection Day 29: MVA-HBV 1 x 10^8 pfu IM injection + nivolumab 0.3 mg/kg IV infusion Day 85: MVA-HBV 1 x 10^8 pfu IM injection + nivolumab 0.3 mg/kg IV infusion
Receives: Biological: ChAdOx1-HBV; Biological: MVA-HBV; Biological: Nivolumab
Experimental: Group 3 ChAdOx1-HBV, MVA-HBV, nivolumab, MVA-HBVExperimentalDay 1: ChAdOx1-HBV 1 x 2.5 10^10 vp IM injection Day 29: MVA-HBV 1 x 10^8 pfu IM injection Day 36: Nivolumab 0.3 mg/kg IV infusion Day 85: MVA-HBV 1 x 10^8 pfu IM injection
Receives: Biological: ChAdOx1-HBV; Biological: MVA-HBV; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The incidence of participants with a greater than 1 log HBsAg

    Percentage of participants with a greater than 1 log HBsAg reduction at 6 months after initiation of therapy

    Measured: 6 months after the initiation of therapy

Secondary outcomes (11)
  1. The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) and ≥Grade 3 related adverse events following study treatment

    The incidence of TEAEs and and ≥Grade 3 related adverse events will be based on the number and percentage of participants with events and number of events.

    TEAEs are defined as all adverse events occurring after study IMP administration; they will be further categorised by Seriousness, Severity (i.e. ≥ Grade 3) and Causality.

    Measured: From each study vaccination for the following 7 days

  2. The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) and ≥Grade 3 related adverse events following administration with nivolumab

    The incidence of TEAEs and ≥Grade 3 related adverse events will be based on the number and percentage of participants with events and number of events.

    TEAEs are defined as all adverse events occurring after study IMP administration with nivolumab; they are further categorised by Seriousness, Severity (i.e. ≥ Grade 3) according to FDA Guidance 70 FR 22664 and Causality.

    Measured: From each study administration with nivolumab for the following 7days

  3. The incidence of participants with Adverse Events of Special Interest (AESIs)

    AESIs specific to this study include pneumonitis, grade 3 or 4 diarrhoea, diabetes, thyroid diseases, colitis, nephritis, immune-related endocrinopathies, myocarditis, immune-related skin conditions, or other unspecified immune-related adverse reactions

    Measured: From study admission (the signature of informed consent) to the end of the study (Month 12)

  4. The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) within each study group

    The incidence of TEAEs will be based on the number and proportion of participants with events and number of events and will be calculated for each of the three study groups

    Measured: From each study administration for the following 7 days

  5. Incidence of participants with potentially clinically significant laboratory signs within each treatment group as assessed by the Investigator

    The incidence of participants will be based upon the number and proportion of patients in each treatment group with clinically significant laboratory signs (haematology and biochemistry, including liver function tests) as assessed by the investigator.

    All laboratory signs will be reported in SI units. If any laboratory sign is considered to be clinically significant i.e. outside laboratory normal reference range, the severity of this sign will be assessed according to the FDA Guidance for Industry 70 FR 22664. Absolute change, change from baseline and worst change for each participant will be calculated.

    The incidence of participants with treatment-emergent, clinically significant laboratory signs and laboratory signs of Grade 3-4 severity will be calculated for each treatment group at each time point

    Measured: Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336

  6. Incidence of participants with potentially clinically significant vital signs within each treatment group as assessed by the Investigator

    The incidence of participants will be based upon the number and proportion of patients in each treatment group with clinically significant vital signs.

    Vital signs will be considered to be potentially clinically significant if they respectively fall below or above the relevant upper and lower limits.

    The incidence of participants with treatment-emergent, clinically significant vital signs will be calculated for each treatment group at each time point.

    Measured: Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336

  7. Number of participants with worst changes from baseline in laboratory hematology parameters

    Hematology laboratory values will be evaluated according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA).

    For all hematology parameters, changes from baseline of at least two severity grades will be calculated for each timepoint at which the laboratory test is conducted throughout the study.

    The number of participants showing shifts of at least two severity grades (as worst change from baseline for each hematology parameter) will be presented within shift tables.

    Measured: Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336

  8. Number of participants with worst changes from baseline in laboratory biochemistry parameters

    Biochemistry laboratory values will be evaluated according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA).

    For all biochemistry parameters, changes from baseline of at least two severity grades will be calculated for each timepoint at which the laboratory test is conducted throughout the study.

    The number of participants showing shifts of at least two severity grades (as worst change from baseline for each biochemistry parameter) will be presented within shift tables.

    Measured: Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336

  9. Number of participants with worst changes from baseline in laboratory urinalysis parameters

    Urinalysis laboratory values will be evaluated according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA).

    For all urinalysis parameters, changes from baseline of at least two severity grades will be calculated for each timepoint at which the laboratory test is conducted throughout the study.

    The number of participants showing shifts of at least two severity grades (as worst change from baseline for each urinalysis parameter) will be presented within shift tables.

    Measured: Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336

  10. Number of participants with worst changes from baseline in vital signs parameters (heart rate, systolic blood pressure, diastolic blood pressure and temperature)

    Worst change is defined as the lowest and highest post-baseline values for heart rate (bradycardia, tachycardia) and systolic blood pressure (hypotension, hypertension), and as the highest post-baseline values for diastolic blood pressure (hypertension) and temperature (fever).

    For all vital signs' measurements, changes from baseline will be calculated for each timepoint at which the vital sign measurement is conducted throughout the study. The number of participants showing worst change from baseline for the vital signs parameters overall will be presented within shift tables.

    Measured: Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336

  11. T cell response to the HBV antigen inserts of VTP-300 as measured by interferon (IFN)-γ enzyme-linked immunospot (ELISpot)

    This will be determined by using PMBCs in IFN-γ ELISpot assays to investigate the breadth of HBV specific T cell responses (defined by number of peptide pools or individual peptides recognised). These data may be used to build immunologic models of the immune system.

    Measured: Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2022
  2. Study start21 Sep 2022
  3. Primary completion13 Jan 2026
  4. Study completion13 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Participants are randomised to the three treatment groups. Allocation to the groups is 1:1:1 allocation.
Masking
None (open label)
Enrolment
121 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05343481
Sponsor's protocol ID
HBV-003
Status last verified
Apr 2026
First submitted
12 Apr 2022
Last updated
30 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ChAdOx1-HBV, MVA-HBV and Nivolumab in people with Chronic Hepatitis B, run by Barinthus Biotherapeutics at 18 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Taiwan, Thailand, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The incidence of participants with a greater than 1 log HBsAg (time frame: 6 months after the initiation of therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2026.

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