Safety and Efficacy Study of Adjuvanted Prophylactic Hepatitis B Vaccine

Exposure to Hepatitis B Virus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01951677
• Other study ID #: HBV002
• Status: Completed
• Phase: Phase 1
• Start date: July 2013
• Est. completion date: May 2019

Study information

• Verified date: May 2019
• Source: Vaxine Pty Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: May 2019
• Est. primary completion date: October 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Exposure to Hepatitis B Virus
• Hepatitis
• Hepatitis A
• Hepatitis B

Intervention

Drug:
• HBsAg
Standard hepatitis B vaccine antigen

Biological:
• PreS HBsAg
preS hepatitis B surface antigen
• Advax-1(TM)
Adjuvant formulated with vaccine antigen
• Advax-2(TM)
Adjuvant formulated with vaccine antigen
• Advax-3(TM)
Adjuvant formulated with vaccine antigen
• Alum
Adjuvant formulated with vaccine antigen

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Adelaide	South Australia

Sponsors (2)

Lead Sponsor	Collaborator
Vaxine Pty Ltd	Flinders Medical Centre

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety	Safety as assessed by incidence of adverse events	12 months
Secondary	Hepatitis B surface antibody geometric mean titer	Geometric mean titer of HBsAg titers	one-month post each immunization and 10 months post-final immunization
Secondary	T cell responses	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	7 days and one month post each immunization and 10 months post-final immunization
Secondary	Efficacy	Seroconversion and seroprotection rates will be compared between groups using titers of antibodies to hepatitis B surface antigen at each major time point	one month post each immunization and 10 months post final immunization