Hepatitis A
Conditions
Brief summary
This is a study to evaluate the immune response and safety of GSK Biologicals 2-dose inactivated hepatitis A vaccine when administered with a measles/mumps/rubella vaccine and a varicella (chickenpox) vaccine in children as young as 15 months of age. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Detailed description
An open, controlled comparison of Havrix™ administered alone or with MMR II and Varivax™. The three groups evaluated are: 1) Havrix™ alone, 2) Havrix™ + MMR II and Varivax™ and 3) MMR II and Varivax™ followed by Havrix™ one month later.
Interventions
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 13 Months
Healthy volunteers
Yes
Inclusion criteria
* Subjects whose parents/guardians are believed by the investigator to be willing to comply with the requirements of the protocol * A male or female child 12 and 13 months of age at the time of entry into the Enrollment Phase * Written informed consent obtained from the parents or guardian of the subject, * Free of obvious health problems as established by medical history and history-directed physical examination before entering into the study, and * Parents/guardian of the subject must have a telephone or be able to be contacted by telephone
Exclusion criteria
* Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 42 days preceding the first dose of study vaccine, or planned use during the study period, Chronic administration (defined as more than 14 days) 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, ≥0.5 mg/kg/day. Inhaled, nasal and topical steroids are allowed.) Planned administration or administration of any vaccine not foreseen by the study protocol during the period 31 days before and 31 days after each dose of study vaccine(s). * Previous vaccination against hepatitis A, * History of hepatitis A, * Known exposure to hepatitis A, * Previous vaccination against measles, mumps, rubella and/or varicella, * History of measles, mumps, rubella and/or varicella, * Known exposure to measles, mumps, rubella and/or varicella within 30 days prior to the start of the study, * Planned chronic use of salicylates during the 6-week period following administration of the doses of study vaccine(s), * 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 HavrixTM, M-M-RII or VARIVAXTM, including 2-phenoxyethanol, neomycin and gelatin, * History of anaphylactic or anaphylactoid reactions to egg proteins, * History of hypersensitivity/allergic reaction to latex. Note: The tip cap and the rubber plunger of the HavrixTM needleless pre-filled syringes contain dry natural latex rubber. * Major congenital defects or serious chronic illness, * Active untreated tuberculosis, * History of significant blood dyscrasias * History of any neurologic disorder (a history of febrile seizures not associated with an underlying neurological disorder does not exclude the subject) * Acute disease 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups. | 31 days following the second dose of Havrix® | Concentrations are given as geometric mean concentrations (GMCs) expressed as milli-international units per milliliter (mIU/mL). |
| Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups | 31 days following the second dose of Havrix® | Anti-HAV antibody cut-off value assessed include 15 milli-international units per milliliter (mIU/mL). |
| Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups | 42 days following the administration of M-M-R®II and VARIVAX® | Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values assessed include 150 milli-international units per milliliter (mIU/mL) for anti-measles antibodies, 28 Effective Dose 50 (ED50) for anti-mumps antibodies and 1:5 for anti-varicella antibodies. |
| Number of Subjects With Vaccine Response for Anti-rubella Antibodies in HAV+MMR+V and MMR+V→HAV Groups | 42 days following administration of M-M-R®II and VARIVAX® | Vaccine response is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off value assessed include 10 milli-international units per milliliter (mIU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentrations Above the Cut-off Value in MMR+V→HAV Group | 31 days following the second dose of Havrix® | Anti-HAV antibody cut-off value assessed include 15 milli-international units per millilitre (mIU/mL). |
| Number of Subjects With Vaccine Response to Havrix® | 31 days following the second dose of Havrix® | Vaccine response was defined as: 1) a detectable anti-hepatitis A virus (HAV) antibody concentration 31 days following the second dose in subjects who were initially seronegative; and 2) a 2-fold increase in anti-HAV antibody concentrations above the pre-study concentration 31 days following the second dose in subjects who were initially seropositive. |
| Number of Subjects Reporting Solicited Local Symptoms | During the 4-day period following each dose of vaccine | Solicited local symptoms assessed include pain, rash (local), redness and swelling. |
| Number of Subjects Reporting Solicited General Symptoms | During the 4-day period following each dose of vaccine | Solicited general symptoms assessed include drowsiness, fever, irritability, loss of appetite and rash (general). |
| Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups | 42 days following the administration of M-M-R®II and VARIVAX® | Titers are given as geometric mean titers (GMTs). |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | During the 31-day period following each dose of vaccine | Unsolicited AE covers any AE 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 |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
| Number of Subjects Reporting New Chronic Illnesses | During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end) | New Chronic illnesses include autoimmune disorders, asthma, type I diabetes, allergies. |
| Number of Subjects Reporting Medically Significant Events | During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end) | Medically significant events include, but are not limited to, diabetes, autoimmune disease, asthma, allergies and/or conditions prompting emergency room or physician office visits that are not related to well-child care, vaccination or common acute illnesses (e.g., upper respiratory infection, otitis media, pharyngitis, gastroenteritis, injury and visits for routine physical examination). |
| Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | During the 43-day period following each dose of vaccine | Specific adverse events assessed include papules, vesicles, crusts, parotid/salivary gland swelling and suspected signs of meningitis/febrile seizures. |
| Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups | 42 days following the first dose of Havrix® | Concentrations are given as geometric mean concentrations (GMCs). |
| Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups | 42 days following the first dose of Havrix® | Anti-HAV antibody cut-off value assessed include 15 milli-international units per millilitre (mIU/mL). |
| Anti-hepatitis A Virus (HAV) Antibody Concentrations in MMR+V→HAV Group | 31 days following the second dose of Havrix® | Concentrations are given as geometric mean concentrations (GMCs). |
Countries
United States
Participant flow
Pre-assignment details
While the total numbers of subjects enrolled in the study was 1474, the total number of subjects that entered the study was 1241. The remaining subjects received a subject number but no vaccine dose and were therefore excluded from the analysis and group assignment.
Participants by arm
| Arm | Count |
|---|---|
| HAV Group Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9) | 324 |
| MMR+V→HAV Group Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5) | 455 |
| HAV+MMR+V Group Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9 | 462 |
| Total | 1,241 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 1 |
| Overall Study | Lost to Follow-up | 28 | 46 | 37 |
| Overall Study | Other | 2 | 3 | 2 |
| Overall Study | Protocol Violation | 0 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 17 | 37 | 34 |
Baseline characteristics
| Characteristic | HAV+MMR+V Group | Total | HAV Group | MMR+V→HAV Group |
|---|---|---|---|---|
| Age, Continuous | 15.0 months STANDARD_DEVIATION 0.25 | 15.0 months STANDARD_DEVIATION 0.25 | 15.0 months STANDARD_DEVIATION 0.27 | 15.0 months STANDARD_DEVIATION 0.22 |
| Sex: Female, Male Female | 232 Participants | 594 Participants | 154 Participants | 208 Participants |
| Sex: Female, Male Male | 230 Participants | 647 Participants | 170 Participants | 247 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 251 / 324 | 366 / 455 | 363 / 462 |
| serious Total, serious adverse events | 7 / 324 | 12 / 455 | 16 / 462 |
Outcome results
Primary
Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups.
Concentrations are given as geometric mean concentrations (GMCs) expressed as milli-international units per milliliter (mIU/mL).
Time frame: 31 days following the second dose of Havrix®
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV and HAV+MMR+V Groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| HAV Group | Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups. | 1390.4 mIU/mL |
| HAV+MMR+V Group | Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups. | 1895.2 mIU/mL |
Primary
Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups
Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values assessed include 150 milli-international units per milliliter (mIU/mL) for anti-measles antibodies, 28 Effective Dose 50 (ED50) for anti-mumps antibodies and 1:5 for anti-varicella antibodies.
Time frame: 42 days following the administration of M-M-R®II and VARIVAX®
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV+MMR+V and MMR+V→HAV groups.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MMR+V→HAV Group | Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups | Anti-varicella | 168 Participants |
| MMR+V→HAV Group | Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups | Anti-measles | 247 Participants |
| MMR+V→HAV Group | Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups | Anti-mumps | 193 Participants |
| HAV+MMR+V Group | Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups | Anti-mumps | 207 Participants |
| HAV+MMR+V Group | Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups | Anti-varicella | 187 Participants |
| HAV+MMR+V Group | Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups | Anti-measles | 267 Participants |
Primary
Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups
Anti-HAV antibody cut-off value assessed include 15 milli-international units per milliliter (mIU/mL).
Time frame: 31 days following the second dose of Havrix®
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV and HAV+MMR+V groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HAV Group | Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups | 204 Participants |
| HAV+MMR+V Group | Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups | 285 Participants |
Primary
Number of Subjects With Vaccine Response for Anti-rubella Antibodies in HAV+MMR+V and MMR+V→HAV Groups
Vaccine response is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off value assessed include 10 milli-international units per milliliter (mIU/mL).
Time frame: 42 days following administration of M-M-R®II and VARIVAX®
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV+MMR+V and MMR+V→HAV groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MMR+V→HAV Group | Number of Subjects With Vaccine Response for Anti-rubella Antibodies in HAV+MMR+V and MMR+V→HAV Groups | 246 Participants |
| HAV+MMR+V Group | Number of Subjects With Vaccine Response for Anti-rubella Antibodies in HAV+MMR+V and MMR+V→HAV Groups | 270 Participants |
Secondary
Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups
Concentrations are given as geometric mean concentrations (GMCs).
Time frame: 42 days following the first dose of Havrix®
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV and HAV+MMR+V groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| HAV Group | Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups | 43.1 milli-international units per milliliter |
| HAV+MMR+V Group | Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups | 43.5 milli-international units per milliliter |
Secondary
Anti-hepatitis A Virus (HAV) Antibody Concentrations in MMR+V→HAV Group
Concentrations are given as geometric mean concentrations (GMCs).
Time frame: 31 days following the second dose of Havrix®
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from MMR+V→HAV Group.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MMR+V→HAV Group | Anti-hepatitis A Virus (HAV) Antibody Concentrations in MMR+V→HAV Group | 1770.3 milli-international units per milliliter |
Secondary
Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups
Titers are given as geometric mean titers (GMTs).
Time frame: 42 days following the administration of M-M-R®II and VARIVAX®
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV+MMR+V and MMR+V→HAV groups.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MMR+V→HAV Group | Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups | Anti-rubella | 88.3 titers |
| MMR+V→HAV Group | Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups | Anti-varicella | 281.7 titers |
| MMR+V→HAV Group | Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups | Anti-mumps | 215.7 titers |
| MMR+V→HAV Group | Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups | Anti-measles | 3218.3 titers |
| HAV+MMR+V Group | Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups | Anti-measles | 3136.3 titers |
| HAV+MMR+V Group | Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups | Anti-rubella | 76.0 titers |
| HAV+MMR+V Group | Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups | Anti-mumps | 170.3 titers |
| HAV+MMR+V Group | Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups | Anti-varicella | 286.9 titers |
Secondary
Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events
Specific adverse events assessed include papules, vesicles, crusts, parotid/salivary gland swelling and suspected signs of meningitis/febrile seizures.
Time frame: During the 43-day period following each dose of vaccine
Population: Analysis was performed on the Total Vaccinated cohort, on subjects from MMR+V→HAV and HAV+MMR+V groups.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MMR+V→HAV Group | Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | Vesicles | 17 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | Parotid/salivary gland swelling | 0 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | Crusts | 12 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | Suspected signs of meningitidis/febrile seizures | 1 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | Papules | 23 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | Suspected signs of meningitidis/febrile seizures | 2 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | Papules | 23 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | Vesicles | 17 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | Crusts | 12 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events | Parotid/salivary gland swelling | 1 Participants |
Secondary
Number of Subjects Reporting Medically Significant Events
Medically significant events include, but are not limited to, diabetes, autoimmune disease, asthma, allergies and/or conditions prompting emergency room or physician office visits that are not related to well-child care, vaccination or common acute illnesses (e.g., upper respiratory infection, otitis media, pharyngitis, gastroenteritis, injury and visits for routine physical examination).
Time frame: During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end)
Population: Analysis was performed on the Total Vaccinated cohort (for the Active Phase) and the Extended Safety Follow-up cohort (for the Extended Safety Follow-up Phase).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HAV Group | Number of Subjects Reporting Medically Significant Events | Extended Safety Follow-Up Phase | 0 Participants |
| HAV Group | Number of Subjects Reporting Medically Significant Events | Active Phase | 0 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Medically Significant Events | Extended Safety Follow-Up Phase | 0 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Medically Significant Events | Active Phase | 0 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Medically Significant Events | Active Phase | 0 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Medically Significant Events | Extended Safety Follow-Up Phase | 0 Participants |
Secondary
Number of Subjects Reporting New Chronic Illnesses
New Chronic illnesses include autoimmune disorders, asthma, type I diabetes, allergies.
Time frame: During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end)
Population: Analysis was performed on the Total Vaccinated cohort (for the Active Phase) and the Extended Safety Follow-up cohort (for the Extended Safety Follow-up Phase).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HAV Group | Number of Subjects Reporting New Chronic Illnesses | Active Phase | 0 Participants |
| HAV Group | Number of Subjects Reporting New Chronic Illnesses | Extended Safety Follow-Up Phase | 0 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting New Chronic Illnesses | Active Phase | 0 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting New Chronic Illnesses | Extended Safety Follow-Up Phase | 0 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting New Chronic Illnesses | Active Phase | 0 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting New Chronic Illnesses | Extended Safety Follow-Up Phase | 0 Participants |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end)
Population: Analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HAV Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Active Phase | 1 Participants |
| HAV Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Extended Safety Follow-up Phase | 6 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Active Phase | 6 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Extended Safety Follow-up Phase | 6 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Active Phase | 5 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Extended Safety Follow-up Phase | 11 Participants |
Secondary
Number of Subjects Reporting Solicited General Symptoms
Solicited general symptoms assessed include drowsiness, fever, irritability, loss of appetite and rash (general).
Time frame: During the 4-day period following each dose of vaccine
Population: Analysis was performed on the Total Vaccinated cohort, on subjects with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HAV Group | Number of Subjects Reporting Solicited General Symptoms | Loss of appetite | 94 Participants |
| HAV Group | Number of Subjects Reporting Solicited General Symptoms | Irritability | 144 Participants |
| HAV Group | Number of Subjects Reporting Solicited General Symptoms | Drowsiness | 95 Participants |
| HAV Group | Number of Subjects Reporting Solicited General Symptoms | Fever | 54 Participants |
| HAV Group | Number of Subjects Reporting Solicited General Symptoms | Rash (general) | 5 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Solicited General Symptoms | Irritability | 238 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Solicited General Symptoms | Drowsiness | 179 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Solicited General Symptoms | Fever | 110 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Solicited General Symptoms | Loss of appetite | 170 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Solicited General Symptoms | Rash (general) | 7 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Solicited General Symptoms | Rash (general) | 10 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Solicited General Symptoms | Loss of appetite | 154 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Solicited General Symptoms | Drowsiness | 178 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Solicited General Symptoms | Irritability | 216 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Solicited General Symptoms | Fever | 80 Participants |
Secondary
Number of Subjects Reporting Solicited Local Symptoms
Solicited local symptoms assessed include pain, rash (local), redness and swelling.
Time frame: During the 4-day period following each dose of vaccine
Population: Analysis was performed on the Total Vaccinated cohort, on subjects with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HAV Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 97 Participants |
| HAV Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 103 Participants |
| HAV Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 45 Participants |
| HAV Group | Number of Subjects Reporting Solicited Local Symptoms | Rash (local) | 0 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 149 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Solicited Local Symptoms | Rash (local) | 3 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 162 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 70 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Solicited Local Symptoms | Rash (local) | 4 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 187 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 82 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 151 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Unsolicited AE covers any AE 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
Time frame: During the 31-day period following each dose of vaccine
Population: Analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HAV Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 186 Participants |
| MMR+V→HAV Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 286 Participants |
| HAV+MMR+V Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 249 Participants |
Secondary
Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups
Anti-HAV antibody cut-off value assessed include 15 milli-international units per millilitre (mIU/mL).
Time frame: 42 days following the first dose of Havrix®
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from HAV and HAV+MMR+V groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HAV Group | Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups | 194 Participants |
| HAV+MMR+V Group | Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups | 276 Participants |
Secondary
Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentrations Above the Cut-off Value in MMR+V→HAV Group
Anti-HAV antibody cut-off value assessed include 15 milli-international units per millilitre (mIU/mL).
Time frame: 31 days following the second dose of Havrix®
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results from MMR+V→HAV Group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MMR+V→HAV Group | Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentrations Above the Cut-off Value in MMR+V→HAV Group | 237 Participants |
Secondary
Number of Subjects With Vaccine Response to Havrix®
Vaccine response was defined as: 1) a detectable anti-hepatitis A virus (HAV) antibody concentration 31 days following the second dose in subjects who were initially seronegative; and 2) a 2-fold increase in anti-HAV antibody concentrations above the pre-study concentration 31 days following the second dose in subjects who were initially seropositive.
Time frame: 31 days following the second dose of Havrix®
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, on subjects with available results.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HAV Group | Number of Subjects With Vaccine Response to Havrix® | 192 Participants |
| MMR+V→HAV Group | Number of Subjects With Vaccine Response to Havrix® | 224 Participants |
| HAV+MMR+V Group | Number of Subjects With Vaccine Response to Havrix® | 257 Participants |