Safety and Immunogenicity of a Paediatric Dose of Virosomal Hepatitis A Vaccine

A Phase II Open, Randomised, Controlled Study to Evaluate the Safety and Immunogenicity of a Paediatric Dose (0.25 mL) and the Standard Dose (0.5 mL) of Epaxal® With Reference to Havrix Junior® Healthy in Healthy Children and Adolescents (>=12 Months - 16 Years of Age) Using a 0/6 Month Schedule

The primary purpose of the original study was to assess whether the protection afforded by the paediatric dose of Epaxal vaccine against hepatitis A was not inferior to the protection afforded by the standard dose of Epaxal. The aim of the follow-up phase was to perform a computer based modelling analysis of the long term protection afforded by the paediatric dose, and to compare this with the standard dose and also with an alternative hepatitis A vaccine (Havrix Junior).

Study Overview

• Status: Completed
• Conditions: Hepatitis A
• Intervention / Treatment: Biological: Epaxal 0.25 mL; Biological: Epaxal 0.5 mL; Biological: Havrix Junior 0.5 mL

• Study Type: Interventional
• Enrollment (Actual): 308
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, B-2018
    • Sint-Vincentiusziekenhuis
  • Antwerp, Belgium, BE-2610
    • Centre for the Evaluation of Vaccination, University of Antwerp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Original study:

• Males or females aged >=12 months and 16 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject when applicable and from the parent/legal guardian of the subject. - Free of obvious health problems as established by medical history and/or clinical examination before entering the study.

Follow up phase:

• Subjects enrolled and randomized in the primary study and having received two doses of the study vaccine

Exclusion Criteria:

• Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period and safety follow-up
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. (For corticosteroids, this means prednisone, or equivalent, >=0.5 mg/kg/day. Inhaled and topical steroids were allowed.)
• Planned administration/administration of a vaccine not foreseen by the study protocol within 4 weeks prior to the first dose of study vaccine
• Previous vaccination against hepatitis A
• Seropositive for anti-HAV antibodies (>=10 mIU/mL)
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Major congenital defects or serious chronic illness
• Acute disease at the time of enrolment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epaxal 0.25 mL; Single intramuscular dose (M. deltoideus) given on Day 1 and at Month 6	Biological: Epaxal 0.25 mL; 12 IU hepatitis A antigen coupled to immunopotentiating reconstituted Influenza virosome (IRIV)
Active Comparator: Epaxal 0.5 mL; Single intramuscular dose (M. deltoideus) given on Day 1 and at Month 6	Biological: Epaxal 0.5 mL; 24 IU hepatitis A antigen coupled to IRIV
Active Comparator: Havrix Junior; Single intramuscular dose (M. deltoideus) given on Day 1 and at Month 6	Biological: Havrix Junior 0.5 mL; 720 EU hepatitis A antigen absorbed onto aluminum hydroxide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual anti-HAV titers	Real-time seroprotection analysis and computer modelling will be conducted up to 5 years post-booster to estimate long term seroprotection	66 months post-booster
Individual anti-HAV titers	Real-time seroprotection analysis and computer modelling will be conducted up to 5 years post-booster to estimate long term seroprotection	18 months post-booster
Individual anti-HAV titers	Real-time seroprotection analysis and computer modelling will be conducted up to 5 years post-booster to estimate long term seroprotection	30 months post-booster
Individual anti-HAV titers	Real-time seroprotection analysis and computer modelling will be conducted up to 5 years post-booster to estimate long term seroprotection	42 months post-booster
Individual anti-HAV titers	Real-time seroprotection analysis and computer modelling will be conducted up to 5 years post-booster to estimate long term seroprotection	54 months post-booster

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titers		18, 30, 42, 54, 66 months post-booster
Seroprotection	Porportion of subjects who are seroprotected calculated at each time point where seroprotection is defined as >=10 mIU/mL	18, 30, 42, 54, 66 months post-booster

Collaborators and Investigators

• Sponsor: Crucell Holland BV
• Investigators: Principal Investigator: Pierre van Damme, MD, Universiteit Antwerpen; Principal Investigator: Andre Vertruyen, MD, Sint-Vincentiusziekenhuis

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: July 28, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): July 29, 2011

Study Record Updates

• Last Update Posted (Estimate): July 29, 2014
• Last Update Submitted That Met QC Criteria: July 28, 2014
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Vaccination; Immunisation; Hepatitis A
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A
• Other Study ID Numbers: EPA 001 FU