Safety and Efficacy Study of Adjuvanted Prophylactic Hepatitis B Vaccine

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

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

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.