Clinical Trials List
Protocol NumberHBV002
2020-05-01 - 2023-02-22
Phase I/II
Not yet recruiting5
Recruiting1
ICD-10B18.1
Chronic viral hepatitis B without delta-agent
ICD-9070.32
Viral hepatitis B without mention of hepatic coma, chronic, without mention of hepatitis delta
A Phase 1b/2a, Open-Label Study to Evalute the Safety, Tolerability and Immunogenicity of VTP-300 with or wuthout Nivoulumab in Participants with Chronic Hepatitis B infecttion
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chung-Feng Huang 無
- 黃駿逸 無
- Ming-Lung Yu 無
- Chia-Yen Dai 無
- Jee-Fu Huang 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
Chronic Hepatitis B
Objectives
Primary Objectives
• Determine the safety and reactogenicity of the following in participants with chronic HBV (CHB)
infection and virally suppressed with oral antiviral medication:
− MVA-HBV vaccine
− ChAdOx1-HBV plus MVA vaccines
− ChAdOx1-HBV plus MVA vaccines and nivolumab
Secondary Objectives
• Determine the immunogenicity of the following in participants with CHB infection and virally
suppressed with oral antiviral medication:
− MVA-HBV vaccine
− ChAdOx1-HBV plus MVA-HBV vaccines
− ChAdOx1-HBV plus MVA-HBV vaccines administered with nivolumab
• Determine the impact of PD-1 blockade timing relative to vaccination on immunogenicity in
participants with CHB infection and virally suppressed with oral antiviral medication
• Determine the effect of the following on the level of hepatitis B markers in participants with CHB
infection and virally suppressed with oral antiviral medication:
ChAdOx1-HBV plus MVA-HBV vaccines without nivolumab
− ChAdOx1-HBV plus MVA-HBV vaccines with nivolumab
Exploratory Objectives
• Assess the HBV specific cellular immune response generated by ChAdOx1-HBV plus MVA-HBV vaccines
• Determine the effect of ChAdOx1 HBV plus MVA-HBV with or without nivolumab on hepatitis B biomarkers
Test Drug
ChAdOx1-HBV; MVA-HBV; Nivolumab
Active Ingredient
ChAdOx1-HBV
MVA-HBV
Nivolumab
MVA-HBV
Nivolumab
Dosage Form
Solution for injection
Solution for injection
Concentrate for solution for infusion
Solution for injection
Concentrate for solution for infusion
Dosage
1 x 10^11
2.0 x 10^8
10
2.0 x 10^8
10
Endpoints
Primary Endpoints
• Safety and reactogenicity of the vaccine(s):
incidence of adverse events, serious adverse events (SAEs), ≥Grade 3 study vaccine-related adverse
events within 4 weeks of vaccination
• Safety of the vaccines with nivolumab: incidence of adverse events, SAEs, ≥Grade 3 adverse events
within 4 weeks of dosing
• Incidence of adverse events of special interest
• Number and proportion of participants reporting treatment-emergent adverse events within each
treatment group
• Number and proportion of participants within each treatment group with potentially clinically
significant laboratory values and vital signs within each treatment group
• Change from baseline in laboratory tests and vital sign measurements to each time point of collection
Secondary Endpoints
• Magnitude and avidity of HBV specific CD4+ and CD8+ T cells induced by each regimen
• Effect on the frequency and magnitude of HBV infection markers (HBsAg, Hepatitis B surface
antibody seroconversion, hepatitis B DNA, HBeAg)
Exploratory Endpoints
Exploratory endpoints may include, but may not be limited to:
• Effect on hepatitis B core-related Ag (HBcrAg)
• Effect on hepatitis B pregenomic RNA (HBpgRNA)
• Induction of individual phenotypic subsets of CD4+and CD8+ T cells induced by vaccination
• The T cell breadth of response to the HBV proteins encoded by the ChAdOx1-HBV plus MVA-HBV vaccines
• Frequency of regulatory T cells responses
• Safety and reactogenicity of the vaccine(s):
incidence of adverse events, serious adverse events (SAEs), ≥Grade 3 study vaccine-related adverse
events within 4 weeks of vaccination
• Safety of the vaccines with nivolumab: incidence of adverse events, SAEs, ≥Grade 3 adverse events
within 4 weeks of dosing
• Incidence of adverse events of special interest
• Number and proportion of participants reporting treatment-emergent adverse events within each
treatment group
• Number and proportion of participants within each treatment group with potentially clinically
significant laboratory values and vital signs within each treatment group
• Change from baseline in laboratory tests and vital sign measurements to each time point of collection
Secondary Endpoints
• Magnitude and avidity of HBV specific CD4+ and CD8+ T cells induced by each regimen
• Effect on the frequency and magnitude of HBV infection markers (HBsAg, Hepatitis B surface
antibody seroconversion, hepatitis B DNA, HBeAg)
Exploratory Endpoints
Exploratory endpoints may include, but may not be limited to:
• Effect on hepatitis B core-related Ag (HBcrAg)
• Effect on hepatitis B pregenomic RNA (HBpgRNA)
• Induction of individual phenotypic subsets of CD4+and CD8+ T cells induced by vaccination
• The T cell breadth of response to the HBV proteins encoded by the ChAdOx1-HBV plus MVA-HBV vaccines
• Frequency of regulatory T cells responses
Inclution Criteria
1. Adult males or females aged ≥18 to ≤65 years at screening (according to
country/local regulations)
2. BMI ≤32kg/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 last dose of study
vaccine
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 post-menopausal, as defined by no menses in ≥1 year)
• Of childbearing potential but agrees to practice highly effective contraception
for 4 weeks prior to study vaccine and 8 weeks after study vaccine. 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
6. Documented evidence of chronic HBV infection (e.g. HBsAg positive ≥6 months
with detectable HBsAg levels at screening)
7. Receipt of only either entecavir, tenofovir (tenofovir alafenamide fumarate or
tenofovir disoproxil fumarate), or besifovir for at least 12 months before screening
8. Virally suppressed (HBV-DNA viral load < 400 IU/mL for ≥ 1 year)
9. HBsAg levels <4000 IU/mL
country/local regulations)
2. BMI ≤32kg/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 last dose of study
vaccine
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 post-menopausal, as defined by no menses in ≥1 year)
• Of childbearing potential but agrees to practice highly effective contraception
for 4 weeks prior to study vaccine and 8 weeks after study vaccine. 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
6. Documented evidence of chronic HBV infection (e.g. HBsAg positive ≥6 months
with detectable HBsAg levels at screening)
7. Receipt of only either entecavir, tenofovir (tenofovir alafenamide fumarate or
tenofovir disoproxil fumarate), or besifovir for at least 12 months before screening
8. Virally suppressed (HBV-DNA viral load < 400 IU/mL for ≥ 1 year)
9. HBsAg levels <4000 IU/mL
Exclusion Criteria
1. Presence of any significant acute or chronic, uncontrolled medical/psychiatric illness
2. Hepatitis C virus (HCV) antibody positive.
3. HIV antibody positive
4. Co-infection with hepatitis D virus
5. Documented cirrhosis or advanced fibrosis indicated by a liver biopsy within
6 months prior to screening.
In the absence of a documented liver biopsy, either 1 of the following:
• 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.
In the event of discordant results between non-invasive methods, the Fibroscan
result will take precedence.
6. 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/µL.
7. A history of liver decompensation (e.g. ascites, encephalopathy or variceal
haemorrhage)
8. Prior hepatocellular carcinoma
9. Chronic liver disease of a non-HBV aetiology
10. History or evidence of autoimmune disease or known immunodeficiency of any
cause.
11. 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
12. Receipt of immunoglobulin or other blood products within 3 months prior to
enrolment
13. Receipt of any investigational drug or vaccine within 3 months prior to screening
14. Any history of receipt of any non-oral adenoviral vaccine
15. Receipt of any live vaccines within 30 days prior to screening
16. Receipt of any inactivated vaccines within 14 days prior to screening,
17. History of allergic disease or reactions likely to be exacerbated by any component of
the vaccine
18. Any history of anaphylaxis in reaction to vaccination
19. 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
20. Current alcohol or substance abuse judged by the Investigator to potentially interfere
with participant safety and compliance
21. Significant cardiac disease or unstable uncontrolled cardiac disease
22. Any laboratory test which is abnormal, and which is deemed by the Investigator to
be clinically significant
23. 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
24. Any other finding that, in the opinion of the Investigator, deems the participant
unsuitable for the study
2. Hepatitis C virus (HCV) antibody positive.
3. HIV antibody positive
4. Co-infection with hepatitis D virus
5. Documented cirrhosis or advanced fibrosis indicated by a liver biopsy within
6 months prior to screening.
In the absence of a documented liver biopsy, either 1 of the following:
• 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.
In the event of discordant results between non-invasive methods, the Fibroscan
result will take precedence.
6. 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/µL.
7. A history of liver decompensation (e.g. ascites, encephalopathy or variceal
haemorrhage)
8. Prior hepatocellular carcinoma
9. Chronic liver disease of a non-HBV aetiology
10. History or evidence of autoimmune disease or known immunodeficiency of any
cause.
11. 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
12. Receipt of immunoglobulin or other blood products within 3 months prior to
enrolment
13. Receipt of any investigational drug or vaccine within 3 months prior to screening
14. Any history of receipt of any non-oral adenoviral vaccine
15. Receipt of any live vaccines within 30 days prior to screening
16. Receipt of any inactivated vaccines within 14 days prior to screening,
17. History of allergic disease or reactions likely to be exacerbated by any component of
the vaccine
18. Any history of anaphylaxis in reaction to vaccination
19. 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
20. Current alcohol or substance abuse judged by the Investigator to potentially interfere
with participant safety and compliance
21. Significant cardiac disease or unstable uncontrolled cardiac disease
22. Any laboratory test which is abnormal, and which is deemed by the Investigator to
be clinically significant
23. 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
24. Any other finding that, in the opinion of the Investigator, deems the participant
unsuitable for the study
The Estimated Number of Participants
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Taiwan
42 participants
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Global
64 participants
