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

NCT04778904 | Completed Phase 1 Results DMC

• 2 other identifiers: HBV-0022020-000190-25
• Study Type: interventional
• Target: 55
• Locations: 3 countries
• Sites: 12

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.

Conditions

Hepatitis B

Outcome Measures

Primary Outcomes (9)

• The Incidence of Participants With Treatment-Emergent Adverse Events (TEAEs) and ≥Grade 3 Study Vaccine-related Adverse Events Following Study Vaccination

  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).

  From each study vaccination for the following 27 days

• The Incidence of Participants With ≥Grade 3 Adverse Events Following Study Vaccination With Nivolumab

  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.

  From each study vaccination with nivolumab for the following 27 days

• The Incidence of Participants With Adverse Events of Special Interest (AESIs)

  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.

  From study admission (the signature of informed consent) to the end of the study (Month 9)

• 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 four study groups.

  From each study vaccination for the following 27 days

• 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.

  From the first vaccination until Month 9 (end of study)

• 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.

  From the first vaccination until Month 9 (end of study)

• 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.

  From baseline till Month 9

• 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.

  From baseline till Month 9

• 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.

  From baseline till Month 9

Secondary Outcomes (6)

• Frequency of HBV-specific CD4+ and CD8+ T Cells Induced by Each Treatment Regimen

  Baseline, Day7, Day28, Day35, Month 3, Month 6, Month 9

• Percentage of Participants With Reduction in HBsAg Titre

  Baseline, Day7, Day28, Day35, Month 3, Month 6, Month 9

• Percentage of Participants With HBsAg and HBeAg Loss

  Baseline, Month 9

• Percentage of Participants With HBsAg Seroconversion

  Baseline and Month 9

• Percentage of Participants With HBeAg Seroconversion

  Baseline and Month 9

Study Arms (4)

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

Biological: MVA-HBV

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

Biological: ChAdOx1-HBV; Biological: MVA-HBV

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

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

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

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

Interventions

ChAdOx1-HBV BIOLOGICAL

Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus vaccine

Group 2 (ChAdOx1-HBV, MVA-HBV); Group 3 (ChAdOx1-HBV, MVA-HBV and nivolumab); Group 4 (ChAdOx1-HBV and nivolumab, MVA-HBV and nivolumab)

MVA-HBV BIOLOGICAL

Modified Vaccinia Ankara-vectored Hepatitis B virus vaccine

Group 1 (MVA-HBV); Group 2 (ChAdOx1-HBV, MVA-HBV); Group 3 (ChAdOx1-HBV, MVA-HBV and nivolumab); Group 4 (ChAdOx1-HBV and nivolumab, MVA-HBV and nivolumab)

Nivolumab BIOLOGICAL

Human immunoglobulin G4 monoclonal antibody

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

Group 3 (ChAdOx1-HBV, MVA-HBV and nivolumab); Group 4 (ChAdOx1-HBV and nivolumab, MVA-HBV and nivolumab)

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 ≤32kg/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 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 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

You may not qualify if:

• Presence of any significant acute or chronic, uncontrolled medical/psychiatric illness
• Hepatitis C virus (HCV) antibody positive.
• HIV antibody positive
• Co-infection with hepatitis D virus
• 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.
• 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.
• A history of liver decompensation (e.g. ascites, encephalopathy or variceal haemorrhage)
• Prior hepatocellular carcinoma
• Chronic liver disease of a non-HBV aetiology
• History or evidence of autoimmune disease or known immunodeficiency of any cause
• Presence of active infection
• Evidence of interstitial lung disease, active pneumonitis, myocarditis, or a history of myocarditis

Sponsors & Collaborators

• Barinthus Biotherapeutics: lead

Study Sites (12)

Pusan National University Hospital

Busan, 492421, South Korea

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Keimyung University Dongsan Hospital

Daegu, 42601, South Korea

Location

Yonsei University College of Medicine

Seoul, 03722, South Korea

Location

Asan Medical Centre

Seoul, 05505, South Korea

Location

The Catholic University of Korea Seoul Saint Mary's Hospital

Seoul, 06591, South Korea

Location

Buddhist Tzu Chi Medical Foundation

Dalin, Chia-Yi County, 62247, Taiwan

Location

E-Da Hospital

Kaohsiung City, Yan-chao District, 82445, Taiwan

Location

Chia-Yi Christian Hospital

Chiayi City, 60002, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

Nottingham University Hospitals NHS Trust

Nottingham, Notts, NG7 2UH, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40932107 DERIVED

MeSH Terms

Conditions

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; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Barinthus Biotherapeutics

clinicaltrials@barinthusbio.com

+44 (0) 1865 818 808

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are randomised to the four treatment groups, as the groups are initiated. Allocation to the groups is 1:1:1:1. 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.

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: March 3, 2021
• Study Start: December 22, 2020
• Primary Completion: February 24, 2023
• Study Completion: February 24, 2023
• Last Updated: August 13, 2024
• Results First Posted: August 13, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); KR (6); TW (4)