Safety and Efficacy Study of Adjuvanted Prophylactic Hepatitis B Vaccine

May 6, 2019 updated by: Vaxine Pty Ltd

Phase 1 Randomized, Controlled, Double-blind Study to Compare the Safety and Effectiveness of Hepatitis B Vaccines in Individuals With Renal Impairment, Diabetes Mellitus or Age Greater Than 40 Years

There is a need for more effective and better-tolerated hepatitis B vaccines for low responder high-risk populations including patients with renal impairment and/or diabetes mellitus and those aged over 40 years. Several approaches are available to enhance the potency of hepatitis B virus vaccines including use of the more highly immunogenic antigens, replacing alum with potentially more effective adjuvants, and increasing the dose of vaccine antigen. A combination of these strategies is being tested in this study to identify the most promising candidate approaches to take forward into advanced clinical development

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Adjuvants are a critical ingredient in most vaccines and act by boosting the immune response to the target protein (e.g. hepatitis B surface antigen (HBsAg)). Despite considerable research, aluminium hydroxide or phosphate compounds (collectively referred to as "alum") remain the dominant adjuvants used in human hepatitis B virus vaccines. There is thus an unmet need for new HBV vaccine adjuvants, in particular, for adjuvants capable of boosting cell-mediated immunity (this is a particular type of immune response where killer T cells are activated that are then able to attack and destroy the infection) as alum, although good at stimulating antibodies is very poor at stimulating cell-mediated immunity. Alum, whilst generally accepted as safe, can be associated with significant local vaccine reactions and this is another reason why newer better-tolerated vaccine adjuvants would be beneficial. This study will compare a range of experimental adjuvant formulations to identify those that provide the safest and most effective enhancement of T- and B-cell immunity against hepatitis B

Study Type

Interventional

Enrollment (Anticipated)

240

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5042
        • Flinders Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 18 years and above
  • Male or female
  • Able to provide written informed consent
  • Willing and able to comply with the protocol for the duration of the study.
  • Has one or more of
  • Age 40 years or above
  • Impaired renal function (creatinine >120 mmol/L or calculated glomerular filtration rate <60mls/min)
  • Diagnosis of diabetes mellitus (any type)

Exclusion Criteria:

  • History of prior hepatitis B vaccination
  • History of serious vaccine allergy if in the opinion of the Investigator this represents a contraindication to hepatitis B vaccination
  • Women of childbearing potential unless using a reliable and appropriate contraceptive method, specifically oral contraceptive pill, intrauterine device or mechanical barrier device.
  • Pregnant or lactating women.
  • History of systemic autoimmune disease including Wegener's granulomatosis, systemic lupus erythematosus, Guillain-Barre, scleroderma or multiple sclerosis.
  • Participation in another clinical trial with an investigational agent within 28 days of the scheduled date of first immunization.
  • Any other serious medical, social or mental condition that, in the opinion of the investigator, would be detrimental to the subjects or the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: HBsAg + alum adjuvant
HBsAg + standard alum adjuvant
Drug: HBsAg
Standard hepatitis B vaccine antigen
Other Names:
  • hepatitis B vaccine based on hepatitis B surface antigen
Biological: Alum
Adjuvant formulated with vaccine antigen
Other Names:
  • Alhydrogel
  • Aluminium hydroxide
EXPERIMENTAL: HBsAg + Advax-1(TM)
HBsAg + Advax-1
Drug: HBsAg
Standard hepatitis B vaccine antigen
Other Names:
  • hepatitis B vaccine based on hepatitis B surface antigen
Biological: Advax-1(TM)
Adjuvant formulated with vaccine antigen
Other Names:
  • Delta inulin adjuvant
EXPERIMENTAL: HBsAg + Advax-2(TM)
HBsAg + Advax-2
Drug: HBsAg
Standard hepatitis B vaccine antigen
Other Names:
  • hepatitis B vaccine based on hepatitis B surface antigen
Biological: Advax-2(TM)
Adjuvant formulated with vaccine antigen
Other Names:
  • Supermix
EXPERIMENTAL: HBsAg + Advax-3(TM)
HBsAg + Advax-3
Drug: HBsAg
Standard hepatitis B vaccine antigen
Other Names:
  • hepatitis B vaccine based on hepatitis B surface antigen
Biological: Advax-3(TM)
Adjuvant formulated with vaccine antigen
ACTIVE_COMPARATOR: preS HBsAg + alum adjuvant
Biological: Alum
Adjuvant formulated with vaccine antigen
Other Names:
  • Alhydrogel
  • Aluminium hydroxide
Biological: PreS HBsAg
preS hepatitis B surface antigen
Other Names:
  • preS hepatitis B surface antigen
EXPERIMENTAL: preS HBsAg + Advax-1(TM)
preS HBsAg + Advax-1
Biological: Advax-1(TM)
Adjuvant formulated with vaccine antigen
Other Names:
  • Delta inulin adjuvant
Biological: PreS HBsAg
preS hepatitis B surface antigen
Other Names:
  • preS hepatitis B surface antigen
EXPERIMENTAL: preS HBsAg + Advax-2(TM)
preS HBsAg + Advax-2
Biological: Advax-2(TM)
Adjuvant formulated with vaccine antigen
Other Names:
  • Supermix
Biological: PreS HBsAg
preS hepatitis B surface antigen
Other Names:
  • preS hepatitis B surface antigen
EXPERIMENTAL: preS HBsAg + Advax-3(TM)
preS HBsAg + Advax-3
Biological: Advax-3(TM)
Adjuvant formulated with vaccine antigen
Biological: PreS HBsAg
preS hepatitis B surface antigen
Other Names:
  • preS hepatitis B surface antigen
ACTIVE_COMPARATOR: high dose preS HBsAg + alum adjuvant
Biological: Alum
Adjuvant formulated with vaccine antigen
Other Names:
  • Alhydrogel
  • Aluminium hydroxide
Biological: PreS HBsAg
preS hepatitis B surface antigen
Other Names:
  • preS hepatitis B surface antigen
EXPERIMENTAL: high dose preS HBsAg + Advax-1(TM)
high dose preS HBsAg + Advax-1
Biological: Advax-1(TM)
Adjuvant formulated with vaccine antigen
Other Names:
  • Delta inulin adjuvant
Biological: PreS HBsAg
preS hepatitis B surface antigen
Other Names:
  • preS hepatitis B surface antigen
EXPERIMENTAL: high dose preS HBsAg + Advax-2(TM)
Biological: Advax-2(TM)
Adjuvant formulated with vaccine antigen
Other Names:
  • Supermix
Biological: PreS HBsAg
preS hepatitis B surface antigen
Other Names:
  • preS hepatitis B surface antigen
EXPERIMENTAL: high dose preS HBsAg + Advax-3(TM)
high dose preS HBsAg + Advax-3
Biological: Advax-3(TM)
Adjuvant formulated with vaccine antigen
Biological: PreS HBsAg
preS hepatitis B surface antigen
Other Names:
  • preS hepatitis B surface antigen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: 12 months
Safety as assessed by incidence of adverse events
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatitis B surface antibody geometric mean titer
Time Frame: one-month post each immunization and 10 months post-final immunization
Geometric mean titer of HBsAg titers
one-month post each immunization and 10 months post-final immunization
T cell responses
Time Frame: 7 days and one month post each immunization and 10 months post-final immunization
HBsAg-specific T cell responses as measured by cytokine enzyme-linked immunospot and carboxyfluorescein diacetate succinimidyl ester T-cell proliferation assay will be compared between groups
7 days and one month post each immunization and 10 months post-final immunization
Efficacy
Time Frame: one month post each immunization and 10 months post final immunization
Seroconversion and seroprotection rates will be compared between groups using titers of antibodies to hepatitis B surface antigen at each major time point
one month post each immunization and 10 months post final immunization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vaxine Pty Ltd

Collaborators

Flinders Medical Centre

Investigators

  • Principal Investigator: Jeffrey Barbara, MBBS PhD, Flinders Medical Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 1, 2013

Primary Completion (ACTUAL)

October 1, 2017

Study Completion (ACTUAL)

May 1, 2019

Study Registration Dates

First Submitted

September 16, 2013

First Submitted That Met QC Criteria

September 23, 2013

First Posted (ESTIMATE)

September 27, 2013

Study Record Updates

Last Update Posted (ACTUAL)

May 7, 2019

Last Update Submitted That Met QC Criteria

May 6, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HBV002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Currently no plan

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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