Long Term Follow-up of a Study to Assess the Safety and Immunogenicity of a Hepatitis A Vaccine Administered With and in the Absence of DTPaHibIPV, OPV and MMR Vaccines

A Phase III Randomised, Open, Controlled Study to Assess the Safety and Immunogenicity of Concomitant Administration of Virosomal Hepatitis A Vaccine (Epaxal®) With DTPaHibIPV, OPV and MMR Vaccines vs. Non-concomitant Administration in 12-15 Month Old Children. Follow-up: Serological Long-term Follow-up of Subjects for up to 42 Months, 5.5 and 7.5 Years After the Second Dose.

The primary purpose of this study was to assess whether the protection afforded by Epaxal vaccine co-administered with diphtheria, tetanus, Bordetella pertussis, Haemophilus influenzae type b, and inactivated polio vaccine(DTPaHibIPV), oral polio vaccine (OPV) and (measles mumps and rubella) MMR vaccines against hepatitis A was not inferior to the protection afforded by Epaxal administered alone. The aim of the follow-up phase is to obtain information on the long term protection afforded by Epaxal, and to compare this with an alternative hepatitis A vaccine (Havrix).

Study Overview

• Status: Completed
• Conditions: Hepatitis A
• Intervention / Treatment: Biological: Epaxal; Biological: Havrix 720

• Study Type: Interventional
• Enrollment (Actual): 327
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Beer-Sheva, Israel
  • Petach-Tikva, Israel

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Original study:

• Written informed consent obtained 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.
• At least 8 kg of body weight at age of 12 months.

Follow-up phase:

• Subjects enrolled and randomised in the original study and having received two doses of the hepatitis A study vaccines.

Exclusion Criteria:

Original study:

• Children not having received 3 documented doses of DTPaHib and polio vaccines during infancy
• Children having received a documented dose of MMR during infancy
• 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 the 30 days safety follow-up after the last dose.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Administration of systemic corticosteroids (inhaled and topical steroids are allowed).
• 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.
• 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.

Follow-up phase:

• Children who had received a hepatitis A antigen containing vaccine since the last visit

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: Group A; Epaxal + concomitant administration of DTPaHibIPV, MMR, OPV	Biological: Epaxal; 0.25ml Epaxal: at least 12 IU hepatitis A antigen coupled to immunopotentiating reconstituted influenza virosomes (IRIV)
Experimental: Group B; Epaxal, with administration of DTPaHibIPV, MMR, OPV one month later	Biological: Epaxal; 0.25ml Epaxal: at least 12 IU hepatitis A antigen coupled to immunopotentiating reconstituted influenza virosomes (IRIV)
Active Comparator: Group C; Havrix 720 + concomitant administration of DTPaHibIPV, MMR	Biological: Havrix 720; 0.5ml Havrix 720: at least 720 EU hepatitis A antigen adsorbed onto aluminium hydroxide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-hepatitis A virus (HAV) antibody concentrations	Individual anti-HAV antibody concentrations determined by enzyme-linked immunosorbent assay	5.5 years
Anti-hepatitis A virus (HAV) antibody concentrations	Individual anti-HAV antibody concentrations determined by enzyme-linked immunosorbent assay	7.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean concentrations (GMC)	GMCs of anti-HAV antibodies	5.5 and 7.5 years
Proportion of seroprotected subjects	Proportion of subjects seroprotected defined as anti-HAV antibody concentrations of at least 10 mIU/ml	5.5 and 7.5 years

Collaborators and Investigators

• Sponsor: Crucell Holland BV
• Investigators: Principal Investigator: Ron Dagan, MD, Soraka Medical Center; Principal Investigator: Shai Ashkenazi, MD, Schneider Children's Medical Center, Israel

Publications and helpful links

General Publications

• Dagan R, Ashkenazi S, Livni G, Go O, Bagchi P, Sarnecki M. Long-term Serologic Follow-up of Children Vaccinated with a Pediatric Formulation of Virosomal Hepatitis A Vaccine Administered With Routine Childhood Vaccines at 12-15 Months of Age. Pediatr Infect Dis J. 2016 Jul;35(7):e220-8. doi: 10.1097/INF.0000000000001176.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2007
• Primary Completion (Actual): July 8, 2013
• Study Completion (Actual): July 8, 2013

Study Registration Dates

• First Submitted: February 28, 2011
• First Submitted That Met QC Criteria: March 1, 2011
• First Posted (Estimate): March 3, 2011

Study Record Updates

• Last Update Posted (Actual): April 8, 2019
• Last Update Submitted That Met QC Criteria: April 4, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Hepatitis A Vaccine; Combined Vaccines; DTP Vaccine; MMR Vaccine
• 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: CR106637; EPA 004 FU (Other Identifier: Crucell Holland BV)