Clinical trial NCT01951677: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Exposure to Hepatitis B Virus
Keywords: hepatitis B virus
vaccine
adjuvant
prophylaxis
Lead sponsor: Vaxine Pty Ltd
Sponsor class: INDUSTRY
Collaborators: name: Flinders Medical Centre
First posted: 2013-09-27
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Primary outcomes:
measure: Safety
timeFrame: 12 months
Secondary outcomes:
measure: Hepatitis B surface antibody geometric mean titer
timeFrame: one-month post each immunization and 10 months post-final immunization
measure: T cell responses
timeFrame: 7 days and one month post each immunization and 10 months post-final immunization
measure: Efficacy
timeFrame: one month post each immunization and 10 months post final immunization
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Flinders Medical Centre
state: South Australia
Study officials:
affiliation: Flinders Medical Centre
name: Jeffrey Barbara, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References: