Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ChAdOx1-HBV · 3 trials · 3 indications
Percentage of participants with a greater than 1 log HBsAg reduction at 6 months after initiation of therapy
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 ≥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 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 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.
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.
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.
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.
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.
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.
Adverse events and/or adverse events leading to study discontinuation. Percentages are based on the number of participants in the Safety Analysis Set.
Serious adverse events related to the study vaccine. Percentages are based on the number of participants in the Safety Analysis Set.
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.
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.
Intracellular cytokine staining analysis to measure IFNγ, produced by HBV antigen or hexon-specific CD8+ T cells in PBMC across study timepoints
| Arm | Type | Description |
|---|---|---|
| Experimental: Group 1 ChAdOx1-HBV, MVA-HBV and nivolumab | EXPERIMENTAL | Day 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 |
| Experimental: Group 2 ChAdOx1-HBV, MVA-HBV and nivolumab, MVA-HBV and nivolumab | EXPERIMENTAL | Day 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 |
| Experimental: Group 3 ChAdOx1-HBV, MVA-HBV, nivolumab, MVA-HBV | EXPERIMENTAL | Day 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 | EXPERIMENTAL | 11 participants who have had 2 doses of either Pfizer/Moderna mRNA COVID 19 vaccine receiving high dose vaccination |
| Name | Type | Description |
|---|---|---|
| ChAdOx1-HBV | BIOLOGICAL | Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus immunotherapeutic |
| MVA-HBV | BIOLOGICAL | Modified Vaccinia Ankara-vectored Hepatitis B virus immunotherapeutic |
| Nivolumab | BIOLOGICAL | Human immunoglobulin G4 monoclonal antibody |
Inclusion Criteria: 1. Adult males or females aged ≥18 to ≤65 years at screening (according to country/local regulations) 2. BMI ≤35 kg/m2 3. Able to provide informed consent indicating they understand the purpose of, and procedures required, for the study and are willing to participate 4. If femal...
ChAdOx1-HBV is an investigational viral vector vaccine being developed for the treatment of Chronic Hepatitis B. It is designed to elicit an immune response against the hepatitis B virus. The drug is currently in Phase 2 clinical development and has not been approved by regulatory authorities.
ChAdOx1-HBV is a viral vector vaccine that uses a modified chimpanzee adenovirus to deliver hepatitis B antigens into cells. This is intended to stimulate a targeted T-cell immune response against the virus. The exact molecular target has not been specified in available data.
ChAdOx1-HBV is being developed by Barinthus Biotherapeutics plc, a biopharmaceutical company listed on NASDAQ under the ticker symbol BRNS. The company is conducting clinical trials to evaluate the vaccine's safety and efficacy in patients with chronic hepatitis B.
ChAdOx1-HBV is currently in Phase 2 clinical development. The drug is investigational and has not received FDA approval. It is being studied for the treatment of Chronic Hepatitis B, with completed Phase 1 and Phase 2 trials.
ChAdOx1-HBV has been studied in three clinical trials: NCT04297917, a Phase 1 first-in-human study in healthy participants and those with chronic hepatitis B; NCT04778904, a Phase 1 study of ChAdOx1-HBV and MVA-HBV vaccines; and NCT05343481, a Phase 2 efficacy trial in chronic hepatitis B. All trials are completed.
ChAdOx1-HBV is a component of the VTP-300 vaccine regimen, which combines ChAdOx1-HBV with MVA-HBV. Clinical trials NCT04778904 and NCT05343481 evaluate VTP-300, which includes ChAdOx1-HBV as part of the treatment approach for chronic hepatitis B.