Immune Response & Safety of a Hepatitis A Vaccine Given Together With a Pneumococcal Vaccine in Healthy Children 15 m of Age

Study Overview
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Brief Summary
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This is a study to evaluate the immunogenicity and safety of GSK Biologicals 2-dose inactivated hepatitis A vaccine when administered with a pneumococcal conjugate vaccine in children as young as 15 months of age.

Detailed Description
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An open, controlled comparison of Havrix administered alone or with Prevnar. The three groups evaluated are: 1) Havrix alone, 2) Havrix plus Prevnar and 3) Prevnar followed by Havrix one month later.

Official Title
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A Phase IIIb, Open, Randomized, Controlled, Multicenter Study of the Immunogenicity and Safety of GSK Biologicals' Inactivated Hepatitis A Vaccine Administered on a 0-6 Mth Schedule Concomitantly With Wyeth Lederle's Pneumococcal Conjugate Vaccine in Healthy Children 15 Months of Age

Conditions
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Hepatitis A

Intervention / Treatment
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* Biological: GSK Biologicals 2-dose inactivated hepatitis A vaccine (Havrix)
* Biological: Prevnar™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female child 12 or 13 months of age at the time of entry into the Enrollment Phase, Free of obvious health problems, Subjects must have previously received three doses of Prevnar in his/her first year of life. Exclusion Criteria: Use of any investigational or non-registered drug or vaccine within 42 days preceding the first dose of study vaccine, or planned use during the study period, Chronic administration of immuno-suppressant or other immune-modifying drugs within six months prior to vaccination or planned administration at any time during the study period. (For corticosteroids, this will mean prednisone, or equivalent, less than 0.5 mg/kg/day. Inhaled, nasal and topical steroids are allowed.), Administration of the ACIP-recommended fourth dose of Prevnar prior to entering the Enrollment Phase of the study, Planned administration or administration of any vaccine not foreseen by the study protocol within the period of 42 days before and 30 days after each dose of study vaccine(s), Previous vaccination against hepatitis A, History of hepatitis A or known exposure to hepatitis A, Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, A family history of congenital, hereditary or infectious immunodeficiency or parental risk factors for HIV infection, History of allergic disease/reactions or hypersensitivity likely to be exacerbated by any component of Havrix (e.g., neomycin, 2-phenoxyethanol) or Prevnar (e.g., diphtheria toxoid), Major congenital defects or serious chronic illness, History of any neurologic disorder (history of febrile seizures not associated with an underlying neurological disorder does not exclude the subject), Acute disease, defined as the presence of a moderate or severe illness with or without fever, at the time of vaccination, Administration of immunoglobulins and/or any blood products within three months prior to the first dose of study vaccine or planned administration at any time during the entire study period.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 13 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Havrix Group<br>Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9. | Biological: GSK Biologicals 2-dose inactivated hepatitis A vaccine (Havrix)<br>* Two doses, administered intramuscularly in the right anterolateral thigh.<br>|
| Experimental: Havrix+Prevnar Group<br>Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9. | Biological: GSK Biologicals 2-dose inactivated hepatitis A vaccine (Havrix)<br>* Two doses, administered intramuscularly in the right anterolateral thigh.<br>Biological: Prevnar™<br>* One dose, administered intramuscularly in the left anterolateral thigh.<br>|
| Active Comparator: Prevnar Havrix Group<br>Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10. | Biological: GSK Biologicals 2-dose inactivated hepatitis A vaccine (Havrix)<br>* Two doses, administered intramuscularly in the right anterolateral thigh.<br>Biological: Prevnar™<br>* One dose, administered intramuscularly in the left anterolateral thigh.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects for Anti-HAV Antibodies | Cut-off values assessed were greater than or equal to (≥) 15 milli-international units per milliliter (mIU/mL) in the sera of subjects seronegative before vaccination. | At one month after Dose 2 of Havrix® vaccine (Month 7-10) | 
| Concentrations for Anti-HAV Antibodies | Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL). | At one month after Dose 2 of Havrix® vaccine (Month 7-10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-19F and Anti-23F Antibody Concentrations | Antibody concentrations against pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL). | At one month after Prevnar™ vaccination (Day 30) | 
| Number of Subjects With an Immune Response to Anti-pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F | The immune response was defined, with respect to anti-pneumococcal response rates, as an antibody concentration equal to or above (≥) 0.05 μg/mL. | At one month after Prevnar™ vaccination (Day 30) | 
| Number of Seropositive Subjects for Anti-HAV Antibodies | Cut-off values assessed were greater than or equal to (≥) 15 mIU/mL in the sera of subjects seronegative before vaccination. | At one month after Dose 1 of Havrix® vaccine (Day 30) | 
| Concentrations for Anti-HAV Antibodies | Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli international units per milliliter (mIU/mL). | At one month after Dose 1 of Havrix® vaccine (Day 30) | 
| Number of Seropositive Subjects for Anti-HAV Antibodies | Cut-off values assessed were greater than or equal to (≥) 15 mIU/mL in the sera of subjects seronegative before vaccination. | At one month after Dose 2 of Havrix® vaccine (Month 8-11) | 
| Concentrations for Anti-HAV Antibodies | Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli international units per milliliter (mIU/mL). | At one month after Dose 2 of Havrix® vaccine (Month 8-11) | 
| Number of Subjects With Vaccine Response to Anti-HAV Antibodies | The vaccine response was defined as: a detectable anti-HAV antibody concentration one month after Dose 2 in subjects who were initially seronegative (antibody concentrations < 15 mIU/mL for anti-HAV); or a 2-fold increase above the pre-vaccination concentration one month after Dose 2 in subjects who were initially seropositive (antibody concentrations ≥ 15 mIU/mL for anti-HAV). | One month after Dose 2 of Havrix® vaccine (Month 7-10/8-10) | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site. | During the 4-day (Day 0-3) follow-up period after each vaccine dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Grade 3 irritability = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Related = symptom assessed by the investigator as related to the vaccination. | During the 4-day (Day 0-3) follow-up period after each vaccine dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. | During the 31-day (Day 0-30) follow-up period | 
| Number of Subjects With Serious Adverse Events (SAEs), New Chronic Illnesses (NCIs) and Medically Significant Events (MSEs) | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. NCIs include autoimmune disorders, asthma, type I diabetes, allergies. MSEs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. | During the Active Phase (from Day 0 to Day 30 after final vaccine dose for each subject) | 
| Number of Subjects With SAEs, NCIs and MSEs | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. NCIs include autoimmune disorders, asthma, type I diabetes, allergies. MSEs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. | During the Extended Safety Follow-up (ESFU) Phase (from Day 30 to 6 months after final vaccine dose) |