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ChAdOx1-HBV Vaccine Safety Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04297917
Recruitment Status : Recruiting
First Posted : March 6, 2020
Last Update Posted : March 13, 2020
Sponsor:
Information provided by (Responsible Party):
Vaccitech Limited

Brief Summary:

This is an open label, non-randomised, dose-escalation study to determine the safety and tolerability of different doses of a single dose vaccination of ChAdOx1 HBV in healthy participants and in participants with chronic hepatitis B virus (CHB) infection and virally suppressed with oral antiviral medication.

During this study 10 healthy volunteers and 12 participants with Chronic Hepatitis B virus infection (on anti-viral drugs to suppress the HBV virus), aged 18-65 years, will receive one intramuscular injection of study drug. All participants will be followed up for up to 6 months (9 visits in total) and will be asked to give a blood sample at each clinic visit.

The aims of the study are to assess the safety of the study drug and to see if the vaccine can induce a strong immune response against the hepatitis B Virus


Condition or disease Intervention/treatment Phase
Hepatitis B Healthy Biological: ChAdOx1-HBV Phase 1

Detailed Description:

This is a first in man human study of a therapeutic vaccine for chronic hepatitis B infection(ChAdOx1-1HBV). The vaccine will be given to participants in a dose escalation strategy (two doses). The study aims to recruit first healthy volunteers (n=10) and then adult patients (n=12) who are chronically infected with HBV and are treated with anti-viral medication, either tenofovir or entecavir with persistent virological control.

Each participant will receive 1 dose of the vaccine (intramuscular injection). Participants (Volunteers & patients) will attend up to 9 study visits in total. The last visit will be 24 weeks after vaccination. The primary endpoint of the study is safety. The secondary endpoint is the assessment of the immune response to hepatitis B that is generated by the vaccine. The study will also determine the effect of ChAdOx1‑HBV on virological and immunological systemic and intrahepatic changes in participants with CHB.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: The participants will be recruited sequentially in 4 cohorts as follows - Cohort 1 - Healthy Volunteers - Low dose Vaccine - 5 participants Cohort 2 - Healthy Volunteers - High dose Vaccine - 5 participants Cohort 3 - Participants with Chronic Hepatitis B infection - Low dose - 6 participants Cohort 4 - Participants with Chronic Hepatitis B infection - High dose - 6 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Monotherapy Study to Evaluate the Safety, Tolerability & Immunogenicity of Vaccination With Candidate Chimpanzee Adenovirus-vectored HepB Virus Vaccine ChAdOx1 HBV in Healthy Participants & Participants With Chronic HepB Infection
Actual Study Start Date : February 10, 2019
Estimated Primary Completion Date : November 30, 2020
Estimated Study Completion Date : November 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Healthy Volunteers with low dose vaccination
5 Healthy Volunteers receiving low dose vaccination
Biological: ChAdOx1-HBV
chimpanzee adenovirus-vectored hepatitis B virus vaccine

Experimental: Healthy Volunteers with high dose vaccination
5 Healthy Volunteers receiving high dose vaccination
Biological: ChAdOx1-HBV
chimpanzee adenovirus-vectored hepatitis B virus vaccine

Experimental: Chronic Hepatitis B participants with low dose vaccination
6 participants with Chronic Hepatitis B infection receiving low dose vaccination
Biological: ChAdOx1-HBV
chimpanzee adenovirus-vectored hepatitis B virus vaccine

Experimental: Chronic Hepatitis B participants with high dose vaccination
6 participants with Chronic Hepatitis B infection receiving high dose vaccination
Biological: ChAdOx1-HBV
chimpanzee adenovirus-vectored hepatitis B virus vaccine




Primary Outcome Measures :
  1. Adverse events [ Time Frame: From screening up to day 7 for solicited AE's, unsolicited events through study completion (on average 6 months) ]
    Adverse events and/or adverse events leading to study discontinuation

  2. Serious adverse events [ Time Frame: from day 0 to up to 6 months ]
    Serious adverse events related to the study vaccine

  3. Grade ≥3 local and systemic reactions [ Time Frame: from day 0 to day 3 ]
    Local reactogenicity - pain, induration, warmth, erythema at the vaccination site Systemic: feverishness, chills, myalgia, fatigue, headache, nausea, arthralgia, malaise



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Adult males or females aged ≥18 to ≤65 years at screening
  2. Body Mass Index ≤30 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 last dose of study vaccine, not breast feeding
  5. If female: Not pregnant, 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, Hormonal (oral, intravaginal, transdermal, implantable or injectable), An intrauterine hormone releasing system, An intrauterine device and Bilateral tubal occlusion

    Healthy participants (cohorts 1 and 2):

  6. Considered to be healthy with no current conditions that may significantly impair participant safety or influence study results, in the opinion of the Investigator

    Participants with well controlled CHB (cohorts 3 and 4):

  7. Documented evidence of chronic HBV infection (e.g. HBsAg positive ≥6 months with detectable HBsAg levels at screening)
  8. Receipt of only either entecavir or tenofovir for at least 12 months before screening
  9. Virally suppressed (HBV DNA <40 IU/mL for ≥6 months)
  10. HBsAg <4000IU/mL

Exclusion Criteria:

  1. Presence of any significant acute or chronic, uncontrolled medical/ psychiatric illness
  2. Hepatitis C virus antibody positive.
  3. Human immunodeficiency virus antibody positive
  4. History or evidence of autoimmune disease or known immunodeficiency of any cause
  5. Prolonged therapy with immunomodulators (e.g. corticosteroids) or biologics (e.g. monoclonal antibodies, interferon) within 3 months of screening
  6. Receipt of immunoglobulin or other blood products within 3 months prior to screening
  7. Receipt of any investigational drug or vaccine within 3 months prior to screening
  8. Any history of receipt of any adenoviral vaccine
  9. Receipt of any live vaccines within 30 days prior to screening
  10. Receipt of any inactivated vaccines within 14 days prior to screening
  11. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
  12. Any history of anaphylaxis in reaction to vaccination
  13. 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
  14. Current alcohol or substance abuse judged by the Investigator to potentially interfere with participant safety and compliance
  15. Significant cardiac disease or unstable uncontrolled cardiac disease
  16. Any laboratory test at screening which is abnormal and which is deemed by the Investigator to be clinically significant
  17. Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study Additionally, for healthy participants (cohorts 1 and 2)
  18. HBsAg positive Additionally, for participants with well controlled CHB (cohorts 3 and 4)
  19. Co infection with hepatitis delta
  20. Documented cirrhosis or advanced fibrosis indicated by a liver biopsy within 6 months prior to screening.

    In the absence of an appropriate liver biopsy, either 1 of the following:

    • Screening Fibroscan with a result >9 kPa within ≤6 months of screening or
    • Screening FibroTest >0.48 and aspartate aminotransferase (AST) to platelet ratio index of >1 In the event of discordant results between non-invasive methods, the Fibroscan result will take precedence.
  21. Alanine transaminase (ALT) >3 × upper limit of normal, international normalised ratio (INR) >1.5 unless the participant was stable on an anticoagulant regimen affecting INR, albumin <35 g/L, total bilirubin >2 mg/dL, platelet count <100,000/mL
  22. A history of liver decompensation (e.g. ascites, encephalopathy or variceal haemorrhage)
  23. Prior or current hepatocellular carcinoma
  24. Chronic liver disease of a non HBV aetiology
  25. Any herbal supplements and or other medicines with potential liver toxicity within the previous 3 months prior to enrolment into this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04297917


Contacts
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Contact: General Enquiries +44 01865 818808 enquiries@vaccitech.co.uk

Locations
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United Kingdom
University Hospital Southampton NHS Foundation Trust Not yet recruiting
Southampton, Hampshire, United Kingdom, SO16 6YD
Contact: Mark Wright, PhD    02380777222 ext 4129    Mark.wright@uhs.nhs.uk   
Oxford University Hospitals Nhs Foundation Trust Not yet recruiting
Oxford, Oxfordshire, United Kingdom, OX3 9DU
Contact: Paola Cicconi, MD    + 44 (0) 1865 611413    paola.cicconi@ndm.ox.ac.uk   
Centre for Clinical Vaccinology and Tropical Medicine (CCVTM) Recruiting
Headington, Oxford, United Kingdom, OX3 7LE
Contact: Paola Cicconi, MD    +441865 611413    paola.cicconi@ndm.ox.uk   
Sponsors and Collaborators
Vaccitech Limited
Investigators
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Principal Investigator: Paola Cicconi, Dr University of Oxford
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Responsible Party: Vaccitech Limited
ClinicalTrials.gov Identifier: NCT04297917    
Other Study ID Numbers: HBV001
First Posted: March 6, 2020    Key Record Dates
Last Update Posted: March 13, 2020
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hepatitis B
Hepatitis
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human