Safety and Efficacy Study of Adjuvanted Prophylactic Hepatitis B Vaccine

Phase 1

Completed

Interventions: Biological: PreS HBsAg
Drug: HBsAg
Biological: Advax-1(TM)
Biological: Advax-2(TM)
Biological: Alum
Biological: Advax-3(TM)

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

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
preS HBsAg + Advax-1(TM)	PreS HBsAg	preS HBsAg + Advax-1
preS HBsAg + Advax-1(TM)	Advax-1(TM)	preS HBsAg + Advax-1
preS HBsAg + Advax-2(TM)	PreS HBsAg	preS HBsAg + Advax-2
HBsAg + Advax-2(TM)	Advax-2(TM)	HBsAg + Advax-2
high dose preS HBsAg + alum adjuvant	PreS HBsAg	high dose preS HBsAg + alum adjuvant
high dose preS HBsAg + Advax-1(TM)	PreS HBsAg	high dose preS HBsAg + Advax-1
HBsAg + alum adjuvant	Alum	HBsAg + standard alum adjuvant
HBsAg + Advax-1(TM)	Advax-1(TM)	HBsAg + Advax-1
high dose preS HBsAg + Advax-2(TM)	PreS HBsAg	high dose preS HBsAg + Advax-2(TM)
high dose preS HBsAg + Advax-3(TM)	Advax-3(TM)	high dose preS HBsAg + Advax-3
preS HBsAg + alum adjuvant	Alum	preS HBsAg + alum adjuvant
preS HBsAg + Advax-2(TM)	Advax-2(TM)	preS HBsAg + Advax-2
high dose preS HBsAg + Advax-1(TM)	Advax-1(TM)	high dose preS HBsAg + Advax-1
high dose preS HBsAg + Advax-3(TM)	PreS HBsAg	high dose preS HBsAg + Advax-3
HBsAg + Advax-3(TM)	Advax-3(TM)	HBsAg + Advax-3
preS HBsAg + alum adjuvant	PreS HBsAg	preS HBsAg + alum adjuvant
preS HBsAg + Advax-3(TM)	Advax-3(TM)	preS HBsAg + Advax-3
high dose preS HBsAg + alum adjuvant	Alum	high dose preS HBsAg + alum adjuvant
preS HBsAg + Advax-3(TM)	PreS HBsAg	preS HBsAg + Advax-3
high dose preS HBsAg + Advax-2(TM)	Advax-2(TM)	high dose preS HBsAg + Advax-2(TM)
HBsAg + Advax-3(TM)	HBsAg	HBsAg + Advax-3
HBsAg + alum adjuvant	HBsAg	HBsAg + standard alum adjuvant
HBsAg + Advax-2(TM)	HBsAg	HBsAg + Advax-2
HBsAg + Advax-1(TM)	HBsAg	HBsAg + Advax-1

Primary Outcome Measures

Name	Time	Method
Safety	12 months	Safety as assessed by incidence of adverse events

Secondary Outcome Measures

Name	Time	Method
Hepatitis B surface antibody geometric mean titer	one-month post each immunization and 10 months post-final immunization	Geometric mean titer of HBsAg titers
T cell responses	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
Efficacy	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

Locations (1): Flinders Medical Centre
🇦🇺
Adelaide, South Australia, Australia