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

Sponsor

Crucell Holland BV (Industry)

Overall Status

Completed

CT.gov ID

NCT01307436

Collaborator

(none)

327

Enrollment

Locations

Arms

75.8

Actual Duration (Months)

163.5

Patients Per Site

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Hepatitis A	Biological: Epaxal Biological: Havrix 720	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

327 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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.

Actual Study Start Date :

Mar 14, 2007

Actual Primary Completion Date :

Jul 8, 2013

Actual Study Completion Date :

Jul 8, 2013

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Anti-hepatitis A virus (HAV) antibody concentrations [5.5 years]
Individual anti-HAV antibody concentrations determined by enzyme-linked immunosorbent assay
Anti-hepatitis A virus (HAV) antibody concentrations [7.5 years]
Individual anti-HAV antibody concentrations determined by enzyme-linked immunosorbent assay

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months to 15 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.