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Safety and Efficacy Study of Adjuvanted Prophylactic Hepatitis B Vaccine

Primary Purpose

Exposure to Hepatitis B Virus

Status

Completed

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

HBsAg

PreS HBsAg

Advax-1(TM)

Advax-2(TM)

Advax-3(TM)

Alum

About this trial

This is an interventional prevention trial for Exposure to Hepatitis B Virus focused on measuring hepatitis B virus, vaccine, adjuvant, prophylaxis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Flinders Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

HBsAg + alum adjuvant

HBsAg + Advax-1(TM)

HBsAg + Advax-2(TM)

HBsAg + Advax-3(TM)

preS HBsAg + alum adjuvant

preS HBsAg + Advax-1(TM)

preS HBsAg + Advax-2(TM)

preS HBsAg + Advax-3(TM)

high dose preS HBsAg + alum adjuvant

high dose preS HBsAg + Advax-1(TM)

high dose preS HBsAg + Advax-2(TM)

high dose preS HBsAg + Advax-3(TM)

Arm Description

HBsAg + standard alum adjuvant

HBsAg + Advax-1

HBsAg + Advax-2

HBsAg + Advax-3

preS HBsAg + alum adjuvant

preS HBsAg + Advax-1

preS HBsAg + Advax-2

preS HBsAg + Advax-3

high dose preS HBsAg + alum adjuvant

high dose preS HBsAg + Advax-1

high dose preS HBsAg + Advax-2(TM)

high dose preS HBsAg + Advax-3

Outcomes

Primary Outcome Measures

Safety

Safety as assessed by incidence of adverse events

Secondary Outcome Measures

Hepatitis B surface antibody geometric mean titer

Geometric mean titer of HBsAg titers

T cell responses

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

Efficacy

Seroconversion and seroprotection rates will be compared between groups using titers of antibodies to hepatitis B surface antigen at each major time point

Full Information

NCT ID

NCT01951677

First Posted

September 16, 2013

Last Updated

May 6, 2019

Sponsor

Vaxine Pty Ltd

Collaborators

Flinders Medical Centre

1. Study Identification

Unique Protocol Identification Number

NCT01951677

Brief Title

Safety and Efficacy Study of Adjuvanted Prophylactic Hepatitis B Vaccine

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

July 2013 (Actual)

Primary Completion Date

October 2017 (Actual)

Study Completion Date

May 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vaxine Pty Ltd

Collaborators

Flinders Medical Centre

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Exposure to Hepatitis B Virus

Keywords

hepatitis B virus, vaccine, adjuvant, prophylaxis

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

HBsAg + alum adjuvant

Arm Type

Active Comparator

Arm Description

HBsAg + standard alum adjuvant

Arm Title

HBsAg + Advax-1(TM)

Arm Type

Experimental

Arm Description

HBsAg + Advax-1

Arm Title

HBsAg + Advax-2(TM)

Arm Type

Experimental

Arm Description

HBsAg + Advax-2

Arm Title

HBsAg + Advax-3(TM)

Arm Type

Experimental

Arm Description

HBsAg + Advax-3

Arm Title

preS HBsAg + alum adjuvant

Arm Type

Active Comparator

Arm Description

preS HBsAg + alum adjuvant

Arm Title

preS HBsAg + Advax-1(TM)

Arm Type

Experimental

Arm Description

preS HBsAg + Advax-1

Arm Title

preS HBsAg + Advax-2(TM)

Arm Type

Experimental

Arm Description

preS HBsAg + Advax-2

Arm Title

preS HBsAg + Advax-3(TM)

Arm Type

Experimental

Arm Description

preS HBsAg + Advax-3

Arm Title

high dose preS HBsAg + alum adjuvant

Arm Type

Active Comparator

Arm Description

high dose preS HBsAg + alum adjuvant

Arm Title

high dose preS HBsAg + Advax-1(TM)

Arm Type

Experimental

Arm Description

high dose preS HBsAg + Advax-1

Arm Title

high dose preS HBsAg + Advax-2(TM)

Arm Type

Experimental

Arm Description

high dose preS HBsAg + Advax-2(TM)

Arm Title

high dose preS HBsAg + Advax-3(TM)

Arm Type

Experimental

Arm Description

high dose preS HBsAg + Advax-3

Intervention Type

Drug

Intervention Name(s)

HBsAg

Other Intervention Name(s)

hepatitis B vaccine based on hepatitis B surface antigen

Intervention Description

Standard hepatitis B vaccine antigen

Intervention Type

Biological

Intervention Name(s)

PreS HBsAg

Other Intervention Name(s)

preS hepatitis B surface antigen

Intervention Description

preS hepatitis B surface antigen

Intervention Type

Biological

Intervention Name(s)

Advax-1(TM)

Other Intervention Name(s)

Delta inulin adjuvant

Intervention Description

Adjuvant formulated with vaccine antigen

Intervention Type

Biological

Intervention Name(s)

Advax-2(TM)

Other Intervention Name(s)

Supermix

Intervention Description

Adjuvant formulated with vaccine antigen

Intervention Type

Biological

Intervention Name(s)

Advax-3(TM)

Intervention Description

Adjuvant formulated with vaccine antigen

Intervention Type

Biological

Intervention Name(s)

Alum

Other Intervention Name(s)

Alhydrogel, Aluminium hydroxide

Intervention Description

Adjuvant formulated with vaccine antigen

Primary Outcome Measure Information:

Title

Safety

Description

Safety as assessed by incidence of adverse events

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Hepatitis B surface antibody geometric mean titer

Description

Geometric mean titer of HBsAg titers

Time Frame

one-month post each immunization and 10 months post-final immunization

Title

T cell responses

Description

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

Time Frame

7 days and one month post each immunization and 10 months post-final immunization

Title

Efficacy

Description

Seroconversion and seroprotection rates will be compared between groups using titers of antibodies to hepatitis B surface antigen at each major time point

Time Frame

one month post each immunization and 10 months post final immunization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey Barbara, MBBS PhD

Organizational Affiliation

Flinders Medical Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

Flinders Medical Centre

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5042

Country

Australia

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Currently no plan

Learn more about this trial

Safety and Efficacy Study of Adjuvanted Prophylactic Hepatitis B Vaccine

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