Safety and Efficacy Study of Adjuvanted Prophylactic Hepatitis B Vaccine

Vaxine

Status and phase: Completed; Phase 1

Conditions: Exposure to Hepatitis B Virus

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01951677

HBV002

Details and patient eligibility

About

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

Full 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

Enrollment: 240 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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240 participants in 12 patient groups

HBsAg + alum adjuvant

Active Comparator group

Description:

HBsAg + standard alum adjuvant

Treatment:

Biological: Alum

Drug: HBsAg

HBsAg + Advax-1(TM)

Experimental group

Description:

HBsAg + Advax-1

Treatment:

Biological: Advax-1(TM)

Drug: HBsAg

HBsAg + Advax-2(TM)

Experimental group

Description:

HBsAg + Advax-2

Treatment:

Biological: Advax-2(TM)

Drug: HBsAg

HBsAg + Advax-3(TM)

Experimental group

Description:

HBsAg + Advax-3

Treatment:

Biological: Advax-3(TM)

Drug: HBsAg

preS HBsAg + alum adjuvant

Active Comparator group

Description:

preS HBsAg + alum adjuvant

Treatment:

Biological: Alum

Biological: PreS HBsAg

preS HBsAg + Advax-1(TM)

Experimental group

Description:

preS HBsAg + Advax-1

Treatment:

Biological: Advax-1(TM)

Biological: PreS HBsAg

preS HBsAg + Advax-2(TM)

Experimental group

Description:

preS HBsAg + Advax-2

Treatment:

Biological: Advax-2(TM)

Biological: PreS HBsAg

preS HBsAg + Advax-3(TM)

Experimental group

Description:

preS HBsAg + Advax-3

Treatment:

Biological: Advax-3(TM)

Biological: PreS HBsAg

high dose preS HBsAg + alum adjuvant

Active Comparator group

Description:

high dose preS HBsAg + alum adjuvant

Treatment:

Biological: Alum

Biological: PreS HBsAg

high dose preS HBsAg + Advax-1(TM)

Experimental group

Description:

high dose preS HBsAg + Advax-1

Treatment:

Biological: Advax-1(TM)

Biological: PreS HBsAg

high dose preS HBsAg + Advax-2(TM)

Experimental group

Description:

high dose preS HBsAg + Advax-2(TM)

Treatment:

Biological: Advax-2(TM)

Biological: PreS HBsAg

high dose preS HBsAg + Advax-3(TM)

Experimental group

Description:

high dose preS HBsAg + Advax-3

Treatment:

Biological: Advax-3(TM)

Biological: PreS HBsAg