Title
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
Phase
Phase 1Lead Sponsor
Vaxine Pty LtdStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Exposure to Hepatitis B VirusIntervention/Treatment
advax pres hbsag ...Study Participants
240There 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
Standard hepatitis B vaccine antigen
preS hepatitis B surface antigen
Adjuvant formulated with vaccine antigen
Adjuvant formulated with vaccine antigen
Adjuvant formulated with vaccine antigen
Adjuvant formulated with vaccine antigen
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
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.
