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Efficacy of VTP-300 in Chronic Hepatitis B Infection

Primary Purpose

Chronic Hepatitis B

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ChAdOx1-HBV
MVA-HBV
Nivolumab
Sponsored by
Vaccitech (UK) Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring HBV, Chronic Hep B

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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
  5. 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)
    • 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
  6. Documented evidence of CHB infection (e.g., HBsAg positive ≥6 months with detectable HBsAg levels at screening; both HBeAg+ and HBeAg- allowed)
  7. Receipt of only either entecavir, tenofovir (tenofovir alafenamide fumarate or tenofovir disoproxil fumarate) or besifovir for at least 6 months before screening
  8. HBV-DNA viral load ≤ 1,000 IU/mL
  9. HBsAg levels > 10 and ≤ 4,000 IU/mL

Exclusion Criteria:

  1. 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
  2. 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
  3. HIV antibody positive and active hepatitis C (antibody positive and then DNA positive)
  4. Co-infection with hepatitis D virus (HDV)
  5. 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).
  6. In the absence of a documented liver biopsy, either 1 of the following (not both):

    • 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.
  7. 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.
  8. A history of liver decompensation (e.g., ascites, encephalopathy or variceal haemorrhage)
  9. Prior hepatocellular carcinoma
  10. 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)
  11. 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
  12. Evidence of interstitial lung disease, active pneumonitis, myocarditis or a history of myocarditis
  13. 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.
  14. Receipt of immunoglobulin or other blood products within 3 months prior to Day 1
  15. Receipt of any investigational drug or vaccine within 3 months prior to Day 1
  16. Receipt of any non-oral adenoviral-based vaccine within 3 months prior to administration of ChAdOx1-HBV on Day 1
  17. Severe reaction to any vaccine, requiring medical attention
  18. Receipt of any live vaccines within 30 days prior to Day 1
  19. Receipt of any inactivated non-live vaccines (e.g., mRNA, inactivated vaccines, toxoid vaccines) within 14 days prior to Day 1
  20. History of severe hypersensitivity or anaphylactic reactions likely to be exacerbated by any component of VTP-300 or nivolumab, including severe allergy to egg
  21. 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
  22. Current alcohol or substance abuse judged by the investigator to potentially interfere with participant safety or compliance
  23. Any laboratory test which is abnormal, and which is deemed by the investigator to be clinically significant
  24. Any other finding that, in the opinion of the investigator, deems the participant unsuitable for the study

Sites / Locations

  • Queen Mary HospitalRecruiting
  • Chia-Yi Christian HospitalRecruiting
  • Kaohsiung Medical University Chung-Ho Memorial HospitalRecruiting
  • China Medical University HospitalRecruiting
  • National Cheng Kung University HospitalRecruiting
  • Linkou Chang Gung Memorial HospitalRecruiting
  • Chulabhorn HospitalRecruiting
  • King Chulalongkorn Memorial HospitalRecruiting
  • HIV Netherlands-Australia-Thailand Research CollaborationRecruiting
  • Maharaj Nakorn Chiang Mai HospitalRecruiting
  • Bamrasnaradura Infectious Diseases InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Experimental: Group 1 ChAdOx1-HBV, MVA-HBV and nivolumab

Experimental: Group 2 ChAdOx1-HBV, MVA-HBV and nivolumab, MVA-HBV and nivolumab

Experimental: Group 3 ChAdOx1-HBV, MVA-HBV, nivolumab, MVA-HBV

Arm Description

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 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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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
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
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
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.
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.
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.
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.
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.
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.

Full Information

First Posted
April 12, 2022
Last Updated
May 2, 2023
Sponsor
Vaccitech (UK) Limited
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1. Study Identification

Unique Protocol Identification Number
NCT05343481
Brief Title
Efficacy of VTP-300 in Chronic Hepatitis B Infection
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 21, 2022 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vaccitech (UK) Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
HBV, Chronic Hep B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Participants are randomised to the three treatment groups. Allocation to the groups is 1:1:1 allocation.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: Group 1 ChAdOx1-HBV, MVA-HBV and nivolumab
Arm Type
Experimental
Arm Description
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
Arm Title
Experimental: Group 2 ChAdOx1-HBV, MVA-HBV and nivolumab, MVA-HBV and nivolumab
Arm Type
Experimental
Arm Description
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
Arm Title
Experimental: Group 3 ChAdOx1-HBV, MVA-HBV, nivolumab, MVA-HBV
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
ChAdOx1-HBV
Intervention Description
Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus immunotherapeutic
Intervention Type
Biological
Intervention Name(s)
MVA-HBV
Intervention Description
Modified Vaccinia Ankara-vectored Hepatitis B virus immunotherapeutic
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo 10mg/ml concentrate for solution for infusion
Intervention Description
Human immunoglobulin G4 monoclonal antibody
Primary Outcome Measure Information:
Title
The incidence of participants with a greater than 1 log HBsAg
Description
Percentage of participants with a greater than 1 log HBsAg reduction at 6 months after initiation of therapy
Time Frame
6 months after the initiation of therapy
Secondary Outcome Measure Information:
Title
The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) and ≥Grade 3 related adverse events following study treatment
Description
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.
Time Frame
From each study vaccination for the following 7 days
Title
The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) and ≥Grade 3 related adverse events following administration with nivolumab
Description
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.
Time Frame
From each study administration with nivolumab for the following 7days
Title
The incidence of participants with Adverse Events of Special Interest (AESIs)
Description
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
Time Frame
From study admission (the signature of informed consent) to the end of the study (Month 12)
Title
The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) within each study group
Description
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
Time Frame
From each study administration for the following 7 days
Title
Incidence of participants with potentially clinically significant laboratory signs within each treatment group as assessed by the Investigator
Description
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
Time Frame
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Title
Incidence of participants with potentially clinically significant vital signs within each treatment group as assessed by the Investigator
Description
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.
Time Frame
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Title
Number of participants with worst changes from baseline in laboratory hematology parameters
Description
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.
Time Frame
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Title
Number of participants with worst changes from baseline in laboratory biochemistry parameters
Description
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.
Time Frame
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Title
Number of participants with worst changes from baseline in laboratory urinalysis parameters
Description
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.
Time Frame
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Title
Number of participants with worst changes from baseline in vital signs parameters (heart rate, systolic blood pressure, diastolic blood pressure and temperature)
Description
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.
Time Frame
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Title
T cell response to the HBV antigen inserts of VTP-300 as measured by interferon (IFN)-γ enzyme-linked immunospot (ELISpot)
Description
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.
Time Frame
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) 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 Exclusion Criteria: 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): 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Margaret Marshall, MD
Phone
01865 818 808
Email
meg.marshall@vaccitech.co.uk
Facility Information:
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Man Fung Yuen
Facility Name
Chia-Yi Christian Hospital
City
Chiayi City
ZIP/Postal Code
60002
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chi-Yi Chen, MD
Phone
+86-5-276-5041
Ext
2535
Email
cych01290@gmail.com
Facility Name
Kaohsiung Medical University Chung-Ho Memorial Hospital
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wan-Long Chuang, MD
Phone
+886-916-892-601
Email
s0932841038@gmail.com
Facility Name
China Medical University Hospital
City
Taichung City
ZIP/Postal Code
404332
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheng-Yuan MD Peng, MD
Facility Name
National Cheng Kung University Hospital
City
Tainan City
ZIP/Postal Code
704
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ting Tsung Chang, MD
Facility Name
Linkou Chang Gung Memorial Hospital
City
Taoyuan City
ZIP/Postal Code
333
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chai-Wei Hsu, MD
Facility Name
Chulabhorn Hospital
City
Bangkok
ZIP/Postal Code
10210
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kunsuda
Facility Name
King Chulalongkorn Memorial Hospital
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pisit Tangkijvanich
Facility Name
HIV Netherlands-Australia-Thailand Research Collaboration
City
Bangkok
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anchalee Avihingsanon
Facility Name
Maharaj Nakorn Chiang Mai Hospital
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Apinya Leerapun, MD
Facility Name
Bamrasnaradura Infectious Diseases Institute
City
Mueang Nonthaburi
ZIP/Postal Code
11000
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suparat Khemnark, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Efficacy of VTP-300 in Chronic Hepatitis B Infection

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