Hepatitis BPhase 1/2NCT04778904
First-In-Human Study of ChAdOx1-HBV & MVA-HBV Vaccines (VTP-300) for Chronic HBV
A Phase 1/2 study testing ChAdOx1-HBV, MVA-HBV and Nivolumab in people with Hepatitis B, run by Barinthus Biotherapeutics at 12 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis B
- What is being tested?
- ChAdOx1-HBV, MVA-HBV and Nivolumab
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 12 sitesin 3 countries
- Study dates
- 22 Dec 2020to 24 Feb 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 ≤32kg/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 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 post menopausal, as defined by no menses in ≥1 year and without an alternative medical cause)
Show all 22Show fewer
- Of childbearing potential but agrees to practice highly effective contraception for 4 weeks prior to study vaccine and 8 weeks after study vaccine 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
- transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation:
- oral
- injectable
- implantable
- An intrauterine device
- Bilateral tubal occlusion
- Documented evidence of chronic HBV infection (e.g. HBsAg positive ≥6 months with detectable HBsAg levels at screening)
- Receipt of only either entecavir, tenofovir (tenofovir alafenamide fumarate or tenofovir disoproxil fumarate), or besifovir for at least 12 months before screening
- Virally suppressed (HBV-DNA viral load < 40 IU/mL for ≥ 1 year)
- HBsAg levels <4000 IU/mL
Who cannot join
- Presence of any significant acute or chronic, uncontrolled medical/psychiatric illness
- Hepatitis C virus (HCV) antibody positive.
- HIV antibody positive
- Co-infection with hepatitis D virus
- Documented cirrhosis or advanced fibrosis indicated by a liver biopsy within 6 months prior to screening (Metavir activity grade A3 and stages F3 and F4; Ishak stages 4-6).
- In the absence of a documented liver biopsy, either 1 of the following (not both):
Show all 29Show fewer
- Screening Fibroscan with a result > 9 kilopascals (kPa) (or the equivalent) within ≤ 6 months of screening, OR
- Screening FibroTest >0.48 and aspartate aminotransferase (AST) to platelet ratio index (APRI) of >1.
- ALT >3 x upper limit of normal (ULN), international normalized ratio (INR) >1.5 unless the participant was stable on an anticoagulant regimen affecting INR, albumin <3.5 g/dL, direct bilirubin >1.5 x ULN, platelet count < 100,000/microlitre.
- A history of liver decompensation (e.g. ascites, encephalopathy or variceal haemorrhage)
- Prior hepatocellular carcinoma
- Chronic liver disease of a non-HBV aetiology
- History or evidence of autoimmune disease or known immunodeficiency of any cause
- Presence of active infection
- Evidence of interstitial lung disease, active pneumonitis, myocarditis, or a history of myocarditis
- Past history of thyroid disorder or abnormal thyroid function at screening that is still active and uncontrolled
- Prolonged therapy with immunomodulators (e.g. corticosteroids such as prednisone > 10 mg/day) or biologics (e.g. monoclonal antibodies, IFN) within 3 months of screening
- Receipt of immunoglobulin or other blood products within 3 months prior to enrolment
- Receipt of any investigational drug or vaccine within 3 months prior to screening
- Receipt of any adenoviral-based 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 severe hypersensitivity or anaphylactic reactions likely to be exacerbated by any component of the vaccine or nivolumab
- 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
- Any laboratory test which is abnormal, and which is deemed by the Investigator to be clinically significant
- Cytotoxic agents, other anti HBV or traditional herbal medicines which, in the opinion of the Investigator, may have activity against HBV within the previous 6 months prior to randomization
- Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
South Korea6 sites
Pusan National University Hospital
Busan, 492421
Kyungpook National University Hospital
Daegu, 41944
Keimyung University Dongsan Hospital
Daegu, 42601
Yonsei University College of Medicine
Seoul, 03722
Asan Medical Centre
Seoul, 05505
The Catholic University of Korea Seoul Saint Mary's Hospital
Seoul, 06591
Taiwan4 sites
Chia-Yi Christian Hospital
Chiayi City, 60002
Buddhist Tzu Chi Medical Foundation
Dalin, Chia-Yi County, 62247
E-Da Hospital
Kaohsiung City, Yan-chao District, 82445
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
United Kingdom2 sites
King's College Hospital NHS Foundation Trust
London, SE5 9RS
Nottingham University Hospitals NHS Trust
Nottingham, Notts, NG7 2UH
About this study
Official title: 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
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.
Read the 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
- Being tested
- ChAdOx1-HBV, MVA-HBV, Nivolumab
- Medical subject headings
- 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 vaccine
MVA-HBVBiological
Modified Vaccinia Ankara-vectored Hepatitis B virus vaccine
NivolumabBiological
Also called Opdivo 10mg/ml concentrate for solution for infusion
Human immunoglobulin G4 monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (MVA-HBV) | Experimental | Day 0: MVA-HBV 1 x 10^8 pfu IM injection Day 28: MVA-HBV 1 x 10^8 pfu IM injection Receives: Biological: MVA-HBV |
| Group 2 (ChAdOx1-HBV, MVA-HBV) | Experimental | Day 0: ChAdOx1-HBV 1 x 2.5 10^10 vp IM injection Day 28: MVA-HBV 1 x 10^8 pfu IM injection Receives: Biological: ChAdOx1-HBV; Biological: MVA-HBV |
| Group 3 (ChAdOx1-HBV, MVA-HBV and nivolumab) | Experimental | Day 0: ChAdOx1-HBV 1 x 2.5 10^10 vp IM injection Day 28: 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 |
| Group 4 (ChAdOx1-HBV and nivolumab, MVA-HBV and nivolumab) | Experimental | Day 0: ChAdOx1-HBV 1 x 2.5 10^10 vp IM injection + nivolumab 0.3 mg/kg IV infusion Day 28: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Incidence of Participants With Treatment-Emergent Adverse Events (TEAEs) and ≥Grade 3 Study Vaccine-related Adverse Events Following Study Vaccination
The incidence of TEAEs and and ≥Grade 3 study vaccine-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 vaccine administration; they will be further categorised by Seriousness, Severity (i.e. ≥ Grade 3) and Causality.
Seriousness of the TEAEs is assessed according to the published FDA criteria (2016).
Severity of the TEAEs will be graded according to the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adults and Volunteers Enrolled in Preventative Vaccine Trials, 2007 (70 FR 22664).
Measured: From each study vaccination for the following 27 days
The Incidence of Participants With ≥Grade 3 Adverse Events Following Study Vaccination With Nivolumab
The incidence of ≥Grade 3 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 vaccine 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 vaccination with nivolumab for the following 27 days
The Incidence of Participants With Adverse Events of Special Interest (AESIs)
The incidence of AESIs will be based on the number and percentage of participants with events and number of events.
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 9)
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 four study groups.
Measured: From each study vaccination for the following 27 days
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: From the first vaccination until Month 9 (end of study)
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: From the first vaccination until Month 9 (end of study)
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: From baseline till Month 9
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: From baseline till Month 9
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: From baseline till Month 9
Secondary outcomes (6)
Frequency of HBV-specific CD4+ and CD8+ T Cells Induced by Each Treatment Regimen
The frequency of HBV-specific CD4+ and CD8+ T cells was determined by stimulating Peripheral Blood Mononuclear Cells (PBMC) with peptide pools corresponding to HBV antigens Core, Polymerase and Surface in an Intracellular Cytokine Staining (ICS) flow cytometry assay. In this assay the percentage of CD4+ or CD8+ expressing cytokines IFNγ, IL-2 or TNFα in response to HBV peptides is measured. Frequencies of antigen-specific cytokine-expressing CD4+ or CD8+ T cells are compared across trial timepoints and treatment groups.
Measured: Baseline, Day7, Day28, Day35, Month 3, Month 6, Month 9
Percentage of Participants With Reduction in HBsAg Titre
This will be determined from samples of PBMCs. The percentage of participants with a HBsAg loss >0.5 log10 and >1.0 log10 will be determined for each vaccine and for each treatment group.
Measured: Baseline, Day7, Day28, Day35, Month 3, Month 6, Month 9
Percentage of Participants With HBsAg and HBeAg Loss
The proportion of participants infected with HBsAg-positive virus at baseline who develop Hepatitis B surface antigen antibody will be determined for each vaccine and for each treatment group.
The proportion of participants infected with HBeAg-positive virus at baseline who develop Hepatitis B e-antigen antibody will be determined for each vaccine and for each treatment group.
Measured: Baseline, Month 9
Percentage of Participants With HBsAg Seroconversion
The proportion of participants infected with HBsAg-positive virus at baseline who become HBsAg negative will be determined for each vaccine and for each treatment group.
The times to seroconversion will be calculated in months.
Measured: Baseline and Month 9
Percentage of Participants With HBeAg Seroconversion
This will be determined from samples of PBMCs. The proportion of participants infected with HBeAg-positive virus at baseline who become HBeAg negative will be determined for each vaccine and for each treatment group.
The times to seroconversion will be calculated in months.
Measured: Baseline and Month 9
Percentage of Participants With Reduction of Hepatitis B DNA
Changes from baseline will be calculated for each vaccine and for each treatment group.
Measured: Baseline, Day 35, Month 3 and Month 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2021
- Study start22 Dec 2020
- Primary completion24 Feb 2023
- Study completion24 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Participants are randomised to the four treatment groups, as the groups are initiated. Allocation to the groups is 1:1:1:1. 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.
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barinthus Biotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04778904
- Sponsor's protocol ID
- HBV-002
- Other IDs
- 2020-000190-25
- Status last verified
- Aug 2024
- First submitted
- 1 Feb 2021
- Last updated
- 13 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang K, Shen Y, Hu C, Xu F, Wang Q, Gao Y, Zhou L. Population Pharmacokinetics and Exposure-Response Analysis of Serplulimab in Small Cell Lung Cancer Patients. Clin Transl Sci. 2025 Sep;18(9):e70322. doi: 10.1111/cts.70322.
PubMed 40932107
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04778904
- Acronym / sponsor ID
- HBV-002
- Conditions
- Hepatitis B
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Barinthus BiotherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 22 Dec 2020 (actual)
- Primary completion
- 24 Feb 2023 (actual)
- Study completion
- 24 Feb 2023 (actual)
- First posted
- 3 Mar 2021 (actual)
- Results
- Posted 13 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Participants are randomised to the four treatment groups, as the groups are initiated. Allocation to the groups is 1:1:1:1. 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.
| Arm | Type | Receives |
|---|---|---|
| Group 1 (MVA-HBV) | Experimental | Biological: MVA-HBVDay 0: MVA-HBV 1 x 10^8 pfu IM injection Day 28: MVA-HBV 1 x 10^8 pfu IM injection |
| Group 2 (ChAdOx1-HBV, MVA-HBV) | Experimental | Biological: ChAdOx1-HBV, Biological: MVA-HBVDay 0: ChAdOx1-HBV 1 x 2.5 10^10 vp IM injection Day 28: MVA-HBV 1 x 10^8 pfu IM injection |
| Group 3 (ChAdOx1-HBV, MVA-HBV and nivolumab) | Experimental | Biological: ChAdOx1-HBV, Biological: MVA-HBV, Biological: NivolumabDay 0: ChAdOx1-HBV 1 x 2.5 10^10 vp IM injection Day 28: MVA-HBV 1 x 10^8 pfu IM injection + nivolumab 0.3 mg/kg IV infusion |
| Group 4 (ChAdOx1-HBV and nivolumab, MVA-HBV and nivolumab) | Experimental | Biological: ChAdOx1-HBV, Biological: MVA-HBV, Biological: NivolumabDay 0: ChAdOx1-HBV 1 x 2.5 10^10 vp IM injection + nivolumab 0.3 mg/kg IV infusion Day 28: MVA-HBV 1 x 10^8 pfu IM injection + nivolumab 0.3 mg/kg IV infusion |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Adult males or females aged ≥18 to ≤65 years at screening (according to country/local regulations)
- BMI ≤32kg/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 and up to 5 months after the last dose of nivolumab
- If female: Not pregnant or breast feeding and one of the following:
Key exclusion criteria (29 listed)
- Presence of any significant acute or chronic, uncontrolled medical/psychiatric illness
- Hepatitis C virus (HCV) antibody positive.
- HIV antibody positive
- Co-infection with hepatitis D virus
- Documented cirrhosis or advanced fibrosis indicated by a liver biopsy within 6 months prior to screening (Metavir activity grade A3 and stages F3 and F4; Ishak stages 4-6).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChAdOx1-HBVChimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus vaccine | Biological | Group 2 (ChAdOx1-HBV, MVA-HBV), Group 3 (ChAdOx1-HBV, MVA-HBV and nivolumab), Group 4 (ChAdOx1-HBV and nivolumab, MVA-HBV and nivolumab) |
| MVA-HBVModified Vaccinia Ankara-vectored Hepatitis B virus vaccine | Biological | Group 1 (MVA-HBV), Group 2 (ChAdOx1-HBV, MVA-HBV), Group 3 (ChAdOx1-HBV, MVA-HBV and nivolumab), Group 4 (ChAdOx1-HBV and nivolumab, MVA-HBV and nivolumab) |
| NivolumabAlso: Opdivo 10mg/ml concentrate for solution for infusionHuman immunoglobulin G4 monoclonal antibody | Biological | Group 3 (ChAdOx1-HBV, MVA-HBV and nivolumab), Group 4 (ChAdOx1-HBV and nivolumab, MVA-HBV and nivolumab) |
Primary outcome
The Incidence of Participants With Treatment-Emergent Adverse Events (TEAEs) and ≥Grade 3 Study Vaccine-related Adverse Events Following Study Vaccination
Time frame: From each study vaccination for the following 27 days
The incidence of TEAEs and and ≥Grade 3 study vaccine-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 vaccine administration; they will be further categorised by Seriousness, Severity (i.e. ≥ Grade 3) and Causality. Seriousness of the TEAEs is assessed according to the published FDA criteria (2016). Severity of the TEAEs will be graded according to the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adults and Volunteers Enrolled in Preventative Vaccine Trials, 2007 (70 FR 22664).
The Incidence of Participants With ≥Grade 3 Adverse Events Following Study Vaccination With Nivolumab
Time frame: From each study vaccination with nivolumab for the following 27 days
The incidence of ≥Grade 3 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 vaccine administration with nivolumab; they are further categorised by Seriousness, Severity (i.e. ≥ Grade 3) according to FDA Guidance 70 FR 22664 and Causality.
The Incidence of Participants With Adverse Events of Special Interest (AESIs)
Time frame: From study admission (the signature of informed consent) to the end of the study (Month 9)
The incidence of AESIs will be based on the number and percentage of participants with events and number of events. 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.
The Incidence of Participants With Treatment-Emergent Adverse Events (TEAEs) Within Each Study Group
Time frame: From each study vaccination for the following 27 days
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 four study groups.
Incidence of Participants With Potentially Clinically Significant Laboratory Signs Within Each Treatment Group as Assessed by the Investigator
Time frame: From the first vaccination until Month 9 (end of study)
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.
Incidence of Participants With Potentially Clinically Significant Vital Signs Within Each Treatment Group as Assessed by the Investigator
Time frame: From the first vaccination until Month 9 (end of study)
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.
Number of Participants With Worst Changes From Baseline in Laboratory Hematology Parameters
Time frame: From baseline till Month 9
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.
Number of Participants With Worst Changes From Baseline in Laboratory Biochemistry Parameters
Time frame: From baseline till Month 9
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.
Number of Participants With Worst Changes From Baseline in Vital Signs Parameters (Heart Rate, Systolic Blood Pressure, Diastolic Blood Pressure and Temperature)
Time frame: From baseline till Month 9
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.
6 secondary outcomes
Frequency of HBV-specific CD4+ and CD8+ T Cells Induced by Each Treatment Regimen
Time frame: Baseline, Day7, Day28, Day35, Month 3, Month 6, Month 9
Percentage of Participants With Reduction in HBsAg Titre
Time frame: Baseline, Day7, Day28, Day35, Month 3, Month 6, Month 9
Percentage of Participants With HBsAg and HBeAg Loss
Time frame: Baseline, Month 9
Percentage of Participants With HBsAg Seroconversion
Time frame: Baseline and Month 9
Percentage of Participants With HBeAg Seroconversion
Time frame: Baseline and Month 9
Percentage of Participants With Reduction of Hepatitis B DNA
Time frame: Baseline, Day 35, Month 3 and Month 9
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40932107Wang K, Shen Y, Hu C, Xu F, Wang Q, Gao Y, Zhou L. Population Pharmacokinetics and Exposure-Response Analysis of Serplulimab in Small Cell Lung Cancer Patients. Clin Transl Sci. 2025 Sep;18(9):e70322. doi: 10.1111/cts.70322.
- Individual participant dataSharing planned: No
Related trials for Hepatitis B
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ChAdOx1-HBV, MVA-HBV and Nivolumab in people with Hepatitis B, run by Barinthus Biotherapeutics at 12 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 22 inclusion and 29 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 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in South Korea, Taiwan, United Kingdom. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 13 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Treatment-Emergent Adverse Events (TEAEs) and ≥Grade 3 Study Vaccine-related Adverse Events Following Study Vaccination (time frame: From each study vaccination for the following 27 days). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04778904, which also lists 1 linked publication.
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 13 Aug 2024.