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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.
This is a first in man human study of a therapeutic vaccine for chronic hepatitis B infection(ChAdOx1-1HBV). The vaccine was given to participants in a dose escalation strategy (two doses). Five healthy participants was administered the low dose first (cohort 1). Dose escalation was only initiated in the next 5 healthy participants (cohort 2) following Safety Monitoring Committee (SMC) review.
Six CHB participants was administered the low dose (cohort 3) before the dose escalation was initiated in the remaining 5 CHB participants (cohort 4).
Twenty-six healthy participants (15 who have received two doses of AZD1222 [cohort 5] and 11 who have received at least two prior doses of Pfizer/Moderna mRNA COVID 19 vaccine [cohort 6]) were dosed in parallel with the high dose used in cohorts 2 and 4.
Each participant received 1 dose of the vaccine (intramuscular injection). Participants (Volunteers & patients) in cohorts 1 to 4 attended up to 9 study visits and cohorts 5 & 6 attended up to 4 visits in total. The last visit was 24 weeks after vaccination for cohorts 1 to 4 and 12 weeks for cohorts 5 & 6.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Volunteers with low dose vaccination | Experimental | 5 Healthy Volunteers receiving low dose vaccination |
|
| Healthy Volunteers with high dose vaccination | Experimental | 5 Healthy Volunteers receiving high dose vaccination |
|
| Chronic Hepatitis B participants with low dose vaccination | Experimental | 6 participants with Chronic Hepatitis B infection receiving low dose vaccination |
|
| Chronic Hepatitis B participants with high dose vaccination | Experimental | 5 participants with Chronic Hepatitis B infection receiving high dose vaccination |
|
| 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. |
|
| Healthy Volunteers who have had Pfizer/Moderna mRNA COVID 19 vaccine |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ChAdOx1-HBV | Biological | chimpanzee adenovirus-vectored hepatitis B virus vaccine |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction in HBsAg Titre Post-vaccination in CHB Participants | For the CHB participants only. HBsAg levels were measured at each scheduled follow-up timepoint (Day 28, Day 56, Day 84 and Day 168). A summary of the change is obtained by summarising the difference in the log-transformed results [log(HbsAg at baseline + 1) - log(HbsAg at follow-up + 1)] and back-transforming to absolute values (IU/mL). The mean change is then the Geometric Mean (GM) ratio, where a GM ratio > 1 is equivalent to a reduction in HbsAg. |
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Inclusion Criteria:
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:
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)
HBsAg <4000IU/mL
Participants with well controlled CHB (cohorts 3 and 4):
7. Documented evidence of chronic HBV infection (e.g. HBsAg positive ≥6 months with detectable HBsAg levels at screening) 8. Receipt of only either entecavir or tenofovir for at least 12 months before screening 9. Virally suppressed (HBV DNA <40 IU/mL for ≥6 months) 10. HBsAg <10000 IU/mL
Healthy participants (cohort 5):
11. Considered to be healthy with no current conditions that may significantly impair participant safety or influence study results, in the opinion of the Investigator 12. Adult males or females aged ≥40 to ≤60 years at screening 13. Completed second dose of COVID-19 AZD1222 vaccine 10 to 18 weeks before enrolment
Healthy participants (cohort 6):
14. Considered to be healthy with no current conditions that may significantly impair participant safety or influence study results, in the opinion of the Investigator
15. Adult males or females aged ≥40 to ≤60 years at screening
16. Received the latest dose of Completed of either Pfizer (Comirnaty®) or Moderna (Spikevax) mRNA COVID 19 vaccine 6 to 30 weeks before enrolment
Exclusion Criteria:
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
Cohorts 5 and 6: Receipt of any adenoviral vaccine (other than AZD1222 per inclusion criterion 13) 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
Any laboratory test at screening 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 Additionally, for healthy participants (cohorts 1, 2, 5 and 6)
HBsAg positive Additionally, for participants with well controlled CHB (cohorts 3 and 4)
Co infection with hepatitis delta
Documented cirrhosis or advanced fibrosis indicated by a liver biopsy within 6 months prior to screening.
In the absence of an appropriate liver biopsy, either 1 of the following:
Alanine transaminase (ALT) >3 × upper limit of normal, international normalised ratio (INR) >1.5 unless the participant was stable on an anticoagulant regimen affecting INR, albumin <35 g/L, total bilirubin >2 mg/dL, platelet count <100,000/mL
A history of liver decompensation (e.g. ascites, encephalopathy or variceal haemorrhage)
Prior or current hepatocellular carcinoma
Chronic liver disease of a non HBV aetiology
Any herbal supplements and or other medicines with potential liver toxicity within the previous 3 months prior to enrolment into this study
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| Name | Affiliation | Role |
|---|---|---|
| Eleanor Barnes, Prof | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Southampton NHS Foundation Trust | Southampton | Hampshire | SO16 6YD | United Kingdom | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37791379 | Derived | 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. |
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Fifty-seven (57) participants were screened. Forty-seven (47) subjects were enrolled and vaccinated. The study consisted of 36 healthy participants and 11 participants with CHB and virally suppressed with oral antiviral medication.
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| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Volunteers With Low Dose Vaccination | 5 Healthy Volunteers receiving low dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| FG001 | Healthy Volunteers With High Dose Vaccination | 5 Healthy Volunteers receiving high dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| FG002 | Chronic Hepatitis B Participants With Low Dose Vaccination | 6 participants with Chronic Hepatitis B infection receiving low dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| FG003 | Chronic Hepatitis B Participants With High Dose Vaccination | 5 participants with Chronic Hepatitis B infection receiving high dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| FG004 | Healthy Volunteers Who Have Had COVID-19 AZD1222 Vaccine Received High Dose Vaccination | 15 participants who have had 2 doses of COVID-19 AZD1222 vaccine ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| FG005 | Healthy Volunteers Who Have Had Pfizer/Moderna mRNA COVID 19 Vaccine Received High Dose Vaccination | 11 participants who have had Pfizer/Moderna mRNA COVID 19 vaccine ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Volunteers With Low Dose Vaccination | 5 Healthy Volunteers receiving low dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| BG001 | Healthy Volunteers With High Dose Vaccination |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Safety analysis Set | Posted | Count of Participants | Participants | 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) |
|
Unsolicited adverse events will be 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). Unsolicited adverse events will be followed until resolved or until participant contact discontinues.
Adverse events were coded using MedDRA. Treatment-emergent adverse events (TEAEs) are defined as those occurring or worsening after the study vaccine administration. TEAEs are summarised by system organ class (SOC) and by preferred term (PT). The incidence of TEAEs is based on the numbers and percentages of participants with events and number of events. TEAEs are further summarised by severity and relationship to study vaccine.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Volunteers With Low Dose Vaccination | 5 Healthy Volunteers receiving low dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site pain | General disorders | MedDRA (22.1) | Systematic Assessment |
[Not specified]
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tom Evan, MD | Vaccitech Plc | +44 01865 591 445 | enquiries@vaccitech.co.uk |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 24, 2021 | Mar 19, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 6, 2022 | Mar 19, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
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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
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| Experimental |
11 participants who have had 2 doses of either Pfizer/Moderna mRNA COVID 19 vaccine receiving high dose vaccination |
|
| Baseline, Day 28, 56, 84 and 168 |
| Loss of Both HBeAg and HBsAg | For the CHB participants only, loss of HBeAg and HBsAg at the End of Study assessment (Day 168) include all CHB participants in the denominator. Numerators include participants with a) detectable HBeAg and HBsAg at the Day 0 pre-dose assessment and b) undetectable HBeAg and HBsAg at the End of Study assessment. | Baseline and Day 168 |
| Proportion of CHB Participants With HBeAg and HBsAg Seroconversion | The seroconversion of HBeAg and HBsAg is defined as loss of response to the antigen (defined as a value below the limit of detection (i.e. Not detected) and development of antibody to either HBeAg or surface antigen (HBsAg) (defined as a measurable value above the limit of detection (i.e. Detected). The number and percentage of CHB participants meeting the criteria for seroconversion will be summarised. | Baseline, Day 28, 56, 84 and 168 |
| Reduction of Hepatitis B DNA Levels in CHB Participants | Change in hepatitis B DNA levels is defined by subtracting the DNA levels at each follow-up visit (Day 28, Day 56, Day 84 and Day 168) from the DNA levels pre-vaccination (Day 0). A positive change is equivalent to a reduction in DNA levels. Any results recorded as Not Detected were replaced with zero prior to summarising while any recorded as Detected or 1 (the limit of detection) were replaced with 0.5, prior to summarising. The denominator is the number of participants in the analysis set. | 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 | CD4+ and CD8+ cells were analyzed at selected baseline and follow up study visits (Day 0, Day 14, Day 28, Day 56, and/or Day 84) using intracellular cytokine staining (ICS) data from a flow cytometer. Outcome 'A Multiparameter Index Made of CD4+Magnitude, CD4+ Avidity and CD8+ Magnitude' was not calculated. | Baseline, 14, 28, 56, and 84 |
| Total T Cell Response to the Core Antigen Encoded by ChAdOx1-HBV as Measured in a Peptide-stimulated ELISpot Assay | This was determined by using PMBCs in IFN-γ ELISpot assays to investigate the breadth of HBV specific T cell responses. Assessment of immune response was based on the number of IFN-γ spot-forming units (SFU) per 10^6 PBMC in response to stimulation with each antigenic peptide pool. For CHB-LD, CHB-HD, HP-LD, HP-HD the background correction is derived by subtracting the relevant DMSO control result and replacing any negative values or values < 25 with zero prior to summarising. | Baseline, Day 14, 28, 56, 84 and 168 |
| Total T Cell Response to the Pol1-Pol4 Antigen Encoded by ChAdOx1-HBV as Measured in a Peptide-stimulated ELISpot Assay | This was determined by using PMBCs in IFN-γ ELISpot assays to investigate the breadth of HBV specific T cell responses. Assessment of immune response was based on the number of IFN-γ spot-forming units (SFU) per 10^6 PBMC in response to stimulation with each antigenic peptide pool. For CHB-LD, CHB-HD, HP-LD, HP-HD the background correction is derived by subtracting the relevant DMSO control result and replacing any negative values or values < 25 with zero prior to summarising. | Baseline, Day 14, 28, 56, 84 and 168 |
| Total T Cell Response to the Pre S1/S2 Surface Antigen Encoded by ChAdOx1-HBV as Measured in a Peptide-stimulated ELISpot Assay | This was determined by using PMBCs in IFN-γ ELISpot assays to investigate the breadth of HBV specific T cell responses. Assessment of immune response was based on the number of IFN-γ spot-forming units (SFU) per 10^6 PBMC in response to stimulation with each antigenic peptide pool. For CHB-LD, CHB-HD, HP-LD, HP-HD the background correction is derived by subtracting the relevant DMSO control result and replacing any negative values or values < 25 with zero prior to summarising. | Baseline, Day 14, 28, 56, 84 and 168 |
| Total T Cell Response to the Sii Surface Antigen Encoded by ChAdOx1-HBV as Measured in a Peptide-stimulated ELISpot Assay | This was determined by using PMBCs in IFN-γ ELISpot assays to investigate the breadth of HBV specific T cell responses. Assessment of immune response was based on the number of IFN-γ spot-forming units (SFU) per 10^6 PBMC in response to stimulation with each antigenic peptide pool. For CHB-LD, CHB-HD, HP-LD, HP-HD the background correction is derived by subtracting the relevant DMSO control result and replacing any negative values or values < 25 with zero prior to summarising. | Baseline, Day 14, 28, 56, 84 and 168 |
| Effect of Prior AZD1222 on the CD4+ T Cell Magnitude and Phenotype as Measured by Multiparameter Flow Cytometry | Intracellular cytokine staining analysis to measure IFNγ, produced by hexon-specific CD4+ T cells in PBMC across study timepoints | Baseline, Day 14, 28, 84 |
| 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 hexon-specific CD8+ T cells in PBMC across study timepoints | Baseline, Day 14, 28, 84 |
| Oxford University Hospitals Nhs Foundation Trust |
| Oxford |
| Oxfordshire |
| OX3 9DU |
| United Kingdom |
| Centre for Clinical Vaccinology and Tropical Medicine (CCVTM) | Headington | Oxford | OX3 7LE | United Kingdom |
| Medicines Evaluations Unit | Manchester | M23 9QZ | United Kingdom |
5 Healthy Volunteers receiving high dose vaccination
ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine
| BG002 | Chronic Hepatitis B Participants With Low Dose Vaccination | 6 participants with Chronic Hepatitis B infection receiving low dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| BG003 | Chronic Hepatitis B Participants With High Dose Vaccination | 5 participants with Chronic Hepatitis B infection receiving high dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| BG004 | Healthy Volunteers Who Have Had COVID-19 AZD1222 Vaccine | 15 participants who have had 2 doses of COVID-19 AZD1222 vaccine ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| BG005 | Healthy Volunteers Who Have Had Pfizer/Moderna mRNA COVID 19 Vaccine | 11 participants who have had Pfizer/Moderna mRNA COVID 19 vaccine ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| BG006 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Height at Screening | Mean | Standard Deviation | cm |
|
| Weight at Screening | Mean | Standard Deviation | kg |
|
| BMI at Screening | Mean | Standard Deviation | kg/m^2 |
|
5 Healthy Volunteers receiving high dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| OG002 | Chronic Hepatitis B Participants With Low Dose Vaccination | 6 participants with Chronic Hepatitis B infection receiving low dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| OG003 | Chronic Hepatitis B Participants With High Dose Vaccination | 5 participants with Chronic Hepatitis B infection receiving high dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| OG004 | Healthy Volunteers Who Have Had COVID-19 AZD1222 Vaccine Received High Dose Vaccination | 15 participants who have had 2 doses of COVID-19 AZD1222 vaccine ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
| OG005 | Healthy Volunteers Who Have Had Pfizer/Moderna mRNA COVID 19 Vaccine Received High Dose Vaccination | 11 participants who have had Pfizer/Moderna mRNA COVID 19 vaccine ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine |
|
|
| Primary | 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. | Safety Analysis Set - all participants who received at least one vaccination. | Posted | Count of Participants | Participants | From day 0 to up to 6 months |
|
|
|
| Primary | 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. | Safety Analysis Set | Posted | Number | participants | From day 0 to day 3 |
|
|
|
| Primary | 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. | Safety Analysis Sets | Posted | Count of Participants | Participants | From day 0 to day 3 |
|
|
|
| Primary | 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 | Not Posted | Baseline, Day 14, 28, 56, 84 | Participants |
| Secondary | Reduction in HBsAg Titre Post-vaccination in CHB Participants | For the CHB participants only. HBsAg levels were measured at each scheduled follow-up timepoint (Day 28, Day 56, Day 84 and Day 168). A summary of the change is obtained by summarising the difference in the log-transformed results [log(HbsAg at baseline + 1) - log(HbsAg at follow-up + 1)] and back-transforming to absolute values (IU/mL). The mean change is then the Geometric Mean (GM) ratio, where a GM ratio > 1 is equivalent to a reduction in HbsAg. | Per Protocol population used for HBsAg changes | Posted | Geometric Mean | Standard Deviation | ratio | Baseline, Day 28, 56, 84 and 168 |
|
|
|
| Secondary | Loss of Both HBeAg and HBsAg | For the CHB participants only, loss of HBeAg and HBsAg at the End of Study assessment (Day 168) include all CHB participants in the denominator. Numerators include participants with a) detectable HBeAg and HBsAg at the Day 0 pre-dose assessment and b) undetectable HBeAg and HBsAg at the End of Study assessment. | Intent to Treat Analysis Set | Posted | Count of Participants | Participants | Baseline and Day 168 |
|
|
|
| Secondary | Proportion of CHB Participants With HBeAg and HBsAg Seroconversion | The seroconversion of HBeAg and HBsAg is defined as loss of response to the antigen (defined as a value below the limit of detection (i.e. Not detected) and development of antibody to either HBeAg or surface antigen (HBsAg) (defined as a measurable value above the limit of detection (i.e. Detected). The number and percentage of CHB participants meeting the criteria for seroconversion will be summarised. | ITT Analysis Set | Posted | Count of Participants | Participants | Baseline, Day 28, 56, 84 and 168 |
|
|
|
| Secondary | Reduction of Hepatitis B DNA Levels in CHB Participants | Change in hepatitis B DNA levels is defined by subtracting the DNA levels at each follow-up visit (Day 28, Day 56, Day 84 and Day 168) from the DNA levels pre-vaccination (Day 0). A positive change is equivalent to a reduction in DNA levels. Any results recorded as Not Detected were replaced with zero prior to summarising while any recorded as Detected or 1 (the limit of detection) were replaced with 0.5, prior to summarising. The denominator is the number of participants in the analysis set. | Immunogenicity Analysis Set | Posted | Mean | Standard Deviation | log 10 IU/ml | Baseline, Day 28, 56, 84 and 168 |
|
|
|
| Secondary | Percentage of CD4+ and CD8+ Expressing IFNγ at Baseline and Days 14, 28, 56, and 84 After Vaccination | CD4+ and CD8+ cells were analyzed at selected baseline and follow up study visits (Day 0, Day 14, Day 28, Day 56, and/or Day 84) using intracellular cytokine staining (ICS) data from a flow cytometer. Outcome 'A Multiparameter Index Made of CD4+Magnitude, CD4+ Avidity and CD8+ Magnitude' was not calculated. | The intention was to correlate the measure to hep B surface antigen response, which was not observed any group. We report available data for CD4+ and CD8+ magnitude from Groups 1, 2, 5, and 6. ICS assays were performed at baseline and at the timepoint of peak total response magnitude where adequate cell numbers were available (Baseline and Day 14, 28, 56, and/or 84 after dosing). No results obtained for Groups 3 and 4 due to insufficient sample volume. Certain time points were not collected. | Posted | Mean | Standard Deviation | Percentage of cells | Baseline, 14, 28, 56, and 84 |
|
|
|
| Secondary | Total T Cell Response to the Core Antigen Encoded by ChAdOx1-HBV as Measured in a Peptide-stimulated ELISpot Assay | This was determined by using PMBCs in IFN-γ ELISpot assays to investigate the breadth of HBV specific T cell responses. Assessment of immune response was based on the number of IFN-γ spot-forming units (SFU) per 10^6 PBMC in response to stimulation with each antigenic peptide pool. For CHB-LD, CHB-HD, HP-LD, HP-HD the background correction is derived by subtracting the relevant DMSO control result and replacing any negative values or values < 25 with zero prior to summarising. | Immunogenicity Analysis Set | Posted | Mean | Standard Deviation | Spot forming units (SFU) per 10^6 PBMC | Baseline, Day 14, 28, 56, 84 and 168 |
|
|
|
| Secondary | Total T Cell Response to the Pol1-Pol4 Antigen Encoded by ChAdOx1-HBV as Measured in a Peptide-stimulated ELISpot Assay | This was determined by using PMBCs in IFN-γ ELISpot assays to investigate the breadth of HBV specific T cell responses. Assessment of immune response was based on the number of IFN-γ spot-forming units (SFU) per 10^6 PBMC in response to stimulation with each antigenic peptide pool. For CHB-LD, CHB-HD, HP-LD, HP-HD the background correction is derived by subtracting the relevant DMSO control result and replacing any negative values or values < 25 with zero prior to summarising. | Immunogenicity Analysis Set | Posted | Mean | Standard Deviation | Spot forming units (SFU) per 10^6 PBMC | Baseline, Day 14, 28, 56, 84 and 168 |
|
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| Secondary | Total T Cell Response to the Pre S1/S2 Surface Antigen Encoded by ChAdOx1-HBV as Measured in a Peptide-stimulated ELISpot Assay | This was determined by using PMBCs in IFN-γ ELISpot assays to investigate the breadth of HBV specific T cell responses. Assessment of immune response was based on the number of IFN-γ spot-forming units (SFU) per 10^6 PBMC in response to stimulation with each antigenic peptide pool. For CHB-LD, CHB-HD, HP-LD, HP-HD the background correction is derived by subtracting the relevant DMSO control result and replacing any negative values or values < 25 with zero prior to summarising. | Immunogenicity Analysis Set | Posted | Mean | Standard Deviation | Spot forming units (SFU) per 10^6 PBMC | Baseline, Day 14, 28, 56, 84 and 168 |
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| Secondary | Total T Cell Response to the Sii Surface Antigen Encoded by ChAdOx1-HBV as Measured in a Peptide-stimulated ELISpot Assay | This was determined by using PMBCs in IFN-γ ELISpot assays to investigate the breadth of HBV specific T cell responses. Assessment of immune response was based on the number of IFN-γ spot-forming units (SFU) per 10^6 PBMC in response to stimulation with each antigenic peptide pool. For CHB-LD, CHB-HD, HP-LD, HP-HD the background correction is derived by subtracting the relevant DMSO control result and replacing any negative values or values < 25 with zero prior to summarising. | Immunogenicity Analysis Set | Posted | Mean | Standard Deviation | Spot forming units (SFU) per 10^6 PBMC | Baseline, Day 14, 28, 56, 84 and 168 |
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| Secondary | Effect of Prior AZD1222 on the CD4+ T Cell Magnitude and Phenotype as Measured by Multiparameter Flow Cytometry | Intracellular cytokine staining analysis to measure IFNγ, produced by hexon-specific CD4+ T cells in PBMC across study timepoints | Immunogenicity Analysis Set | Posted | Mean | Standard Deviation | Mean CD4+ IFNy+ T cells | Baseline, Day 14, 28, 84 |
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| Secondary | 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 hexon-specific CD8+ T cells in PBMC across study timepoints | Immunogenicity Analysis Set | Posted | Mean | Standard Deviation | Mean CD8+ IFNy+ T cells | Baseline, Day 14, 28, 84 |
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|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 1 |
| 5 |
| EG001 | Healthy Volunteers With High Dose Vaccination | 5 Healthy Volunteers receiving high dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine | 0 | 5 | 0 | 5 | 4 | 5 |
| EG002 | Chronic Hepatitis B Participants With Low Dose Vaccination | 6 participants with Chronic Hepatitis B infection receiving low dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine | 0 | 6 | 0 | 6 | 2 | 6 |
| EG003 | Chronic Hepatitis B Participants With High Dose Vaccination | 5 participants with Chronic Hepatitis B infection receiving high dose vaccination ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine | 0 | 5 | 0 | 5 | 4 | 5 |
| EG004 | Healthy Volunteers Who Have Had COVID-19 AZD1222 Vaccine Received High Dose Vaccination | 15 participants who have had 2 doses of COVID-19 AZD1222 vaccine ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine | 0 | 15 | 0 | 15 | 8 | 15 |
| EG005 | Healthy Volunteers Who Have Had Pfizer/Moderna mRNA COVID 19 Vaccine Received High Dose Vaccination | 11 participants who have had Pfizer/Moderna mRNA COVID 19 vaccine ChAdOx1-HBV: chimpanzee adenovirus-vectored hepatitis B virus vaccine | 0 | 11 | 0 | 11 | 8 | 11 |
| Injection site swelling | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Injection site rash | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Injection site warmth | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Erythrma | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Blister | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Urticaria papular | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (22.1) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (22.1) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Laparoscopic surgery | Surgical and medical procedures | MedDRA (22.1) | Systematic Assessment |
|
Not provided
| D004266 |
| DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| No Events |
|
| Redness - Grade ≥3 Local reactions |
|
| Pain - Grade ≥3 Local reactions |
|
| Warmth - Grade ≥3 Local reactions |
|
| 1 = No interference with daily activities |
|
| 2 = Some interference with daily activities |
|
| 3 = Significant interference with daily activities |
|
| 4 = ER visit or hospitalisation |
|
| Muscle Ache |
|
| Fatigue |
|
| Headache |
|
| Nausea |
|
| Feverishness |
|
| Chills |
|
| Joint Ache |
|
| Malaise |
|
| Day 84 |
|
| Day 168 |
|
| HBeAg Seroconversion |
|
| Day 56 |
|
| Day 84 |
|
| Day 168 |
|
|
| CD4+ (Day 14) |
|
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| CD4+ (Day 28) |
|
|
| CD4+ (Day 56) |
|
|
| CD4+ (Day 84) |
|
|
| CD8+ (Day 0) |
|
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| CD8+ (Day 14) |
|
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| CD8+ (Day 28) |
|
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| CD8+ (Day 56) |
|
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| CD8+ (Day 84) |
|
|
|
| Day 14 |
|
|
| Day28 |
|
|
| Day 56 |
|
|
| Day 84 |
|
|
| Day 168 |
|
|
|
| Day 14 |
|
|
| Day 28 |
|
|
| Day 56 |
|
|
| Day 84 |
|
|
| Day 168 |
|
|
|
| Day 14 |
|
|
| Day 28 |
|
|
| Day 56 |
|
|
| Day 84 |
|
|
| Day 168 |
|
|
|
| Day 14 |
|
|
| Day 28 |
|
|
| Day 56 |
|
|
| Day 84 |
|
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| Day 168 |
|
|
| CD4+ IFNy+ Day 28 |
|
| CD4+ IFNy+ Day 84 |
|
| CD8+ IFNy+ Day 28 |
|
| CD8+ IFNy+ Day 84 |
|