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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
240

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: 12 months
Safety as assessed by incidence of adverse events
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vaxine Pty Ltd

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Flinders Medical Centre

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 16, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 23, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 27, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 7, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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