First-In-Human Study of ChAdOx1-HBV & MVA-HBV Vaccines (VTP-300) for Chronic HBV

NCT ID: NCT04778904

Last Updated: 2024-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-22
• Study Completion Date: 2023-02-24

Brief Summary

This is an open-label study to determine the safety, tolerability and immunogenicity of ChAdOx1-HBV and MVA-HBV vaccines, with or without nivolumab, in patients with chronic HBV who are virally suppressed with oral anti-viral therapies.

Detailed Description

This is a multi-centre study conducted in 52 participants, who will each be administered 2 vaccine injections (IM) on Day 0 and Day 28 as follows:

Group 1: MVA-HBV + MVA-HBV (now closed) Group 2: ChAdOx1-HBV + MVA-HBV Group 3: ChAdOx1-HBV + MVA-HBV + nivolumab (IV infusion) Group 4: ChAdOx1-HBV + nivolumab + MVA-HBV + nivolumab (now closed)

Participants are randomised to treatment as the groups are initiated with a 1:1:1:1 allocation. Version 6.0 of the study protocol has closed Groups 1 and 4 to further randomisation; recruitment will now be in a 1:1 ratio between Groups 2 and 3 only. A sentinel participant is dosed in Group 1, with further participants in Group 1 only being dosed at least 48h later. Group 2 is initiated following a Day 7 safety assessment of the first 6 participants in Group 1. Groups 3 and 4 are initiated following a Day 7 safety assessment of the first 6 participants in Group 2.

The primary objective of the study is to determine the safety and reactogenicity of the treatment regimens; this will be assessed by analysis of the incidence and severity of (serious) adverse events and any changes in laboratory values and vital signs.

The secondary objectives of the study are the determination of the immunogenicity of the ChAdOx1-HBV and MVA-HBV vaccines and the impact of PD-blockade, as well as the effect on HBV markers; these are assessed by measurements of the magnitude and avidity of HBV-specific CD4+ and CD8+ T cells and the magnitude of HBV markers.

Following first vaccination, participants remain in the study for 9 months and attend clinic visits for vaccination and assessments on Days 0, 7, 28, 35 and Months, 3, 6 and 9.

Conditions

Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1 (MVA-HBV)

Day 0: MVA-HBV 1 x 10\^8 pfu IM injection Day 28: MVA-HBV 1 x 10\^8 pfu IM injection

Group Type: EXPERIMENTAL

MVA-HBV

Intervention Type: BIOLOGICAL

Modified Vaccinia Ankara-vectored Hepatitis B virus vaccine

Group 2 (ChAdOx1-HBV, MVA-HBV)

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 Type: EXPERIMENTAL

ChAdOx1-HBV

Intervention Type: BIOLOGICAL

Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus vaccine

MVA-HBV

Intervention Type: BIOLOGICAL

Modified Vaccinia Ankara-vectored Hepatitis B virus vaccine

Group 3 (ChAdOx1-HBV, MVA-HBV and nivolumab)

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 Type: EXPERIMENTAL

ChAdOx1-HBV

Intervention Type: BIOLOGICAL

Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus vaccine

MVA-HBV

Intervention Type: BIOLOGICAL

Modified Vaccinia Ankara-vectored Hepatitis B virus vaccine

Nivolumab

Intervention Type: BIOLOGICAL

Human immunoglobulin G4 monoclonal antibody

Group 4 (ChAdOx1-HBV and nivolumab, MVA-HBV and nivolumab)

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

Group Type: EXPERIMENTAL

ChAdOx1-HBV

Intervention Type: BIOLOGICAL

Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus vaccine

MVA-HBV

Intervention Type: BIOLOGICAL

Modified Vaccinia Ankara-vectored Hepatitis B virus vaccine

Nivolumab

Intervention Type: BIOLOGICAL

Human immunoglobulin G4 monoclonal antibody

Interventions

ChAdOx1-HBV

Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus vaccine

Intervention Type: BIOLOGICAL

MVA-HBV

Modified Vaccinia Ankara-vectored Hepatitis B virus vaccine

Intervention Type: BIOLOGICAL

Nivolumab

Human immunoglobulin G4 monoclonal antibody

Intervention Type: BIOLOGICAL

Other Intervention Names

Opdivo 10mg/ml concentrate for solution for infusion

Eligibility Criteria

Inclusion 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 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 post menopausal, 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 study vaccine and 5 months after the last dose of nivolumab. Highly effective methods of contraception include one or more of the following:

(i) 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

(ii) Combined (oestrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation:

• oral
• intravaginal
• transdermal

(iii) Progestogen-only hormonal contraception associated with inhibition of ovulation:

• oral
• injectable
• implantable

(iv) An intrauterine device

(v) 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 < 40 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 (Metavir activity grade A3 and stages F3 and F4; Ishak stages 4-6).

In the absence of a documented liver biopsy, either 1 of the following (not both):

• 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.

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/microlitre.

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. Presence of active infection

12. Evidence of interstitial lung disease, active pneumonitis, myocarditis, or a history of myocarditis

13. Past history of thyroid disorder or abnormal thyroid function at screening that is still active and uncontrolled

14. 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

15. Receipt of immunoglobulin or other blood products within 3 months prior to enrolment

16. Receipt of any investigational drug or vaccine within 3 months prior to screening

17. Receipt of any adenoviral-based vaccine within 3 months prior to administration of ChAdOx1-HBV on Day 0, or plan to receive an adenoviral-based vaccine within 3 months after Day 0

18. Receipt of any live vaccines within 30 days prior to screening

19. Receipt of any inactivated vaccines within 14 days prior to screening,

20. History of severe hypersensitivity or anaphylactic reactions likely to be exacerbated by any component of the vaccine or nivolumab

21. 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

22. Current alcohol or substance abuse judged by the Investigator to potentially interfere with participant safety and compliance

23. Significant cardiac disease or unstable uncontrolled cardiac disease

24. Any laboratory test which is abnormal, and which is deemed by the Investigator to be clinically significant

25. 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

26. Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Barinthus Biotherapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Pusan National University Hospital

Busan, , South Korea

Kyungpook National University Hospital

Daegu, , South Korea

Keimyung University Dongsan Hospital

Daegu, , South Korea

Yonsei University College of Medicine

Seoul, , South Korea

Asan Medical Centre

Seoul, , South Korea

The Catholic University of Korea Seoul Saint Mary's Hospital

Seoul, , South Korea

Buddhist Tzu Chi Medical Foundation

Dalin, Chia-Yi County, Taiwan

E-Da Hospital

Kaohsiung City, Yan-chao District, Taiwan

Chia-Yi Christian Hospital

Chiayi City, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Nottingham University Hospitals NHS Trust

Nottingham, Notts, United Kingdom

King's College Hospital NHS Foundation Trust

London, , United Kingdom

Countries

South Korea; Taiwan; United Kingdom

References

Wang K, Shen Y, Hu C, Xu F, Wang Q, Gao Y, Zhou L. Population Pharmacokinetics and Exposure-Response Analysis of Serplulimab in Small Cell Lung Cancer Patients. Clin Transl Sci. 2025 Sep;18(9):e70322. doi: 10.1111/cts.70322.

Reference Type: DERIVED

PMID: 40932107 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-000190-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HBV-002

Identifier Type: -

Identifier Source: org_study_id