Efficacy of VTP-300 in Chronic Hepatitis B Infection

NCT05343481 | Completed Phase 2 DMC

• 1 other identifier: HBV-003
• Study Type: interventional
• Target: 121
• Locations: 3 countries
• Sites: 18

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.

Conditions

Chronic Hepatitis B

Keywords

HBV, Chronic Hep B

Outcome Measures

Primary Outcomes (1)

• 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

  6 months after the initiation of therapy

Secondary Outcomes (11)

• The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) and ≥Grade 3 related adverse events following study treatment

  From each study vaccination for the following 7 days

• The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) and ≥Grade 3 related adverse events following administration with nivolumab

  From each study administration with nivolumab for the following 7days

• The incidence of participants with Adverse Events of Special Interest (AESIs)

  From study admission (the signature of informed consent) to the end of the study (Month 12)

• The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) within each study group

  From each study administration for the following 7 days

• Incidence of participants with potentially clinically significant laboratory signs within each treatment group as assessed by the Investigator

  Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336

Study Arms (3)

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

Biological: ChAdOx1-HBV; Biological: MVA-HBV; Biological: Nivolumab

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

Biological: ChAdOx1-HBV; Biological: MVA-HBV; Biological: Nivolumab

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

Biological: ChAdOx1-HBV; Biological: MVA-HBV; Biological: Nivolumab

Interventions

ChAdOx1-HBV BIOLOGICAL

Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus immunotherapeutic

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

MVA-HBV BIOLOGICAL

Modified Vaccinia Ankara-vectored Hepatitis B virus immunotherapeutic

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

Nivolumab BIOLOGICAL

Human immunoglobulin G4 monoclonal antibody

Also known as: Opdivo 10mg/ml concentrate for solution for infusion

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Barinthus Biotherapeutics: lead

Study Sites (18)

Prince Of Wales Hospital

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Chia-Yi Christian Hospital

Chiayi City, Taiwan, 60002, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung, Taiwan, 807, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan, 404332, Taiwan

Location

National Cheng Kung University Hospital

Tainan, Taiwan, 704, Taiwan

Location

Linkou Chang Gung Memorial Hospital

Taoyuan City, Taiwan, 333, Taiwan

Location

Dalin Tzu Chi Hospital

Chiayi City, Taiwan

Location

Chang Gung Memorial Hospital Kaohsiung

Kaohsiung City, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Chulabhorn Hospital

Bangkok, Thailand, 10210, Thailand

Location

King Chulalongkorn Memorial Hospital

Bangkok, Thailand, 10330, Thailand

Location

HIV Netherlands-Australia-Thailand Research Collaboration

Bangkok, Thailand, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, Thailand, 50200, Thailand

Location

Bamrasnaradura Infectious Diseases Institute

Nonthaburi, Thailand, 11000, Thailand

Location

Hospital For Tropical Diseases

Bangkok, Thailand

Location

Research Institute For Health Sciences

Chiang Mai, Thailand

Location

Srinagarind Hospital

Khon Kaen, Thailand

Location

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

Nivolumab; Solutions

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are randomised to the three treatment groups. Allocation to the groups is 1:1:1 allocation.

Study Record Dates

• First Submitted: April 12, 2022
• First Posted: April 25, 2022
• Study Start: September 21, 2022
• Primary Completion: January 13, 2026
• Study Completion: January 13, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

HK (2); TW (8); TH (8)