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

Study Overview
=================
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).

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.

Conditions
-----------------
Hepatitis A

Intervention / Treatment
-----------------
* Biological: Epaxal
* Biological: Havrix 720


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 12 Months
Maximum Age: 15 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Epaxal + concomitant administration of DTPaHibIPV, MMR, OPV | Biological: Epaxal<br>* 0.25ml Epaxal: at least 12 IU hepatitis A antigen coupled to immunopotentiating reconstituted influenza virosomes (IRIV)<br>|
| Experimental: Group B<br>Epaxal, with administration of DTPaHibIPV, MMR, OPV one month later | Biological: Epaxal<br>* 0.25ml Epaxal: at least 12 IU hepatitis A antigen coupled to immunopotentiating reconstituted influenza virosomes (IRIV)<br>|
| Active Comparator: Group C<br>Havrix 720 + concomitant administration of DTPaHibIPV, MMR | Biological: Havrix 720<br>* 0.5ml Havrix 720: at least 720 EU hepatitis A antigen adsorbed onto aluminium hydroxide<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis A Vaccine, Combined Vaccines, DTP Vaccine, MMR Vaccine