Hepatitis A
Conditions
Keywords
Hepatitis A
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 diphtheria, tetanus and pertussis combination (DTaP) vaccine and a Haemophilus influenza type B (Hib) vaccine in children 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 Infanrix™ and ActHIB. The three groups evaluated are: 1) Havrix™ alone, 2) Havrix™ + Infanrix™ and ActHIB and 3) Infanrix™ and ActHIB 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 or 13 months of age at the time of entry into the Enrolment Phase, * Subjects must have previously received three doses each of DTaP and Hib vaccines during the first year of life. The three doses of DTaP vaccine must have been administered as either Infanrix™ or Pediarix™ and the three doses of Hib vaccine must have been administered as ActHIB™, HibTITER™, OmniHIB™. * Subjects who, at 15 months of age, will have had at least six months elapse since their third dose of Infanrix™ or Pediarix™, * 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 31 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. * Planned administration or administration of any vaccine not foreseen by the study protocol during the period 42 days before and 31 days after each dose of study vaccine(s). * Previous vaccination against DTaP using a commercially-available brand other than Infanrix™ or Pediarix™ or against Hib using a commercially-available brand other than ActHIB™, HibTITER™ or OmniHIB™. * Previous vaccination with more than three doses of DTaP-containing vaccines or more than three doses of Hib-containing vaccines. * Previous vaccination against hepatitis A, * History or known exposure to hepatitis A, * History of diphtheria, tetanus, pertussis and/or Haemophilus influenza type b, * Known exposure to diphtheria, tetanus, pertussis and/or Haemophilus influenza type b within 31 days prior to the start of the study, * History of non-response to any vaccine in the current routine immunization schedule, * 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™, Infanrix™ or ActHIB™ including 2-phenoxyethanol, neomycin and gelatin, * History of hypersensitivity/allergic reaction to latex * Major congenital defects or serious chronic illness, * History of any neurologic disorder * 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, i.e., the Enrolment Phase, the Active Phase and the Extended Safety Follow-up Phase
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the Second Dose of Havrix | 31 days following the second dose of Havrix™ | Subjects are defined as being anti-HAV seropositive if their anti-HAV antibody concentration is ≥ 15 milli-International Units per milliliter (mIU/mL). |
| Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects | 31 days following the administration of Infanrix™ and ActHIB | Subjects are defined as being anti-diphtheria, anti-tetanus and anti-PRP seroprotected if their anti-diphtheria and anti-tetanus antibody concentration is ≥ 0.1 International Units per milliliter (IU/mL) and if their anti-PRP antibody concentration is ≥ 1 microgram per milliliter (μg/mL), respectively. |
| Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN) | 31 days following the administration of Infanrix™ and ActHIB | Subjects are considered as being vaccine responders if they were initially seronegative and become seropositive (≥ 5 Enzyme Linked Immunosorbent Assay Units per Milliliter (EL.U/mL)), or were initially seropositive and have a 2-fold increase above pre-study concentrations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the First Dose of Havrix | 31 days following the first dose of Havrix™ | Subjects are defined as being anti-HAV seropositive if their anti-HAV antibody concentration is ≥ 15 milli-International Units per milliliter (mIU/mL). |
| Anti-hepatitis A Virus (HAV) Antibody Geometric Mean Concentrations (GMC) Following the First Dose of Havrix | 31 days following the first dose of Havrix™ | Anti-hepatitis A (HAV) antibody geometric mean concentrations (GMC) are expressed as milli-International Units per milliliter (mIU/mL). |
| Anti-hepatitis Virus A (HAV) Antibody Geometric Mean Concentrations (GMC) Following the Second Dose of Havrix | 31 days following the second dose of Havrix™ | Anti-hepatitis A (HAV) antibody geometric mean concentrations (GMC) are expressed as milli-International Units per milliliter (mIU/mL). |
| Number of Subjects With Vaccine Response to Havrix™. | 31 days following the second dose | Vaccine response to Havrix is defined as post-vaccination anti-HAV antibody concentrations ≥ 15 mIU/mL in initially seronegative subjects or a ≥ 2-fold increase above the pre-vaccination anti-HAV antibody concentration in initially seropositive subjects. |
| Anti-diphtheria and Anti-tetanus Antibody Geometric Mean Concentrations (GMC) | 31 days following the administration of Infanrix™ and ActHIB | GMCs are expressed as International Units per milliliter (IU/mL). |
| Number of Subjects Reporting Solicited General Adverse Events (AEs) | 4-day period following each dose of study vaccine(s) | Solicited general AEs assessed include drowsiness, axillary fever ≥ 37.5°C, irritability and loss of appetite. Data across doses are presented in the table. |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 31-day period following each dose of study vaccine(s) | An Adverse Event is 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. |
| Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | Active Phase and the 6-months Extended Safety Follow-up (ESFU) Phase. | Since the related information about medically significant events was not specifically collected and new chronic illnesses were only collected in the extended safety follow-up phase, all unsolicited adverse events (AEs) throughout the study are reported in the table without identifying which event was a medically significant or new chronic illness. |
| Number of Subjects Reporting Solicited Local Adverse Events (AEs) | 4-day period following each dose of study vaccine(s) | Solicited local AEs assessed include pain, redness and swelling. Data across doses are presented in the table. |
| Anti-polyribosylribitol Phosphate (PRP) Antibody Geometric Mean Concentrations (GMC) | 31 days following the administration of Infanrix™ and ActHIB | GMCs are expressed as microgram/milliliter (µg/mL). |
| Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) | 31 days following the administration of Infanrix™ and ActHIB | Seropositivity is defined as antibody concentrations ≥ 5 Enzyme Linked Immunosorbent Assay Units per Milliliter (EL.U/mL) for anti-PT, anti-FHA and anti-PRN antibodies and as antibody concentrations ≥ 0.15 microgram/milliliter (µg/mL) for anti-PRP antibodies. |
Countries
United States
Participant flow
Pre-assignment details
Of the total of 468 subjects enrolled, only 394 were vaccinated and as such considered as 'started'.
Participants by arm
| Arm | Count |
|---|---|
| Havrix Group Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9. | 135 |
| Havrix + Infanrix + ActHIB Group Subjects received one dose of Havrix co-administered with Infanrix and ActHIB vaccines at Day 0 followed by a second dose of Havrix at Month 6-9. | 127 |
| Infanrix + ActHIB→Havrix Group Subjects received Infanrix co-administered with ActHIB at Day 0, followed by one dose of Havix at Day 30 and a second dose of Havrix at Month 7-10. | 132 |
| Total | 394 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 5 | 14 | 6 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Returned out of specified time window | 0 | 0 | 1 |
| Overall Study | Study drug/medication expiration | 1 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 7 | 3 | 11 |
Baseline characteristics
| Characteristic | Havrix Group | Havrix + Infanrix + ActHIB Group | Infanrix + ActHIB→Havrix Group | Total |
|---|---|---|---|---|
| Age, Continuous | 15.1 months STANDARD_DEVIATION 0.36 | 15.1 months STANDARD_DEVIATION 0.3 | 15.0 months STANDARD_DEVIATION 0.21 | 15.1 months STANDARD_DEVIATION 0.3 |
| Sex: Female, Male Female | 55 Participants | 64 Participants | 67 Participants | 186 Participants |
| Sex: Female, Male Male | 80 Participants | 63 Participants | 65 Participants | 208 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 | 95 / 135 | 105 / 127 | 107 / 132 |
| serious Total, serious adverse events | 5 / — | 2 / — | 4 / — |
Outcome results
Primary
Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects
Subjects are defined as being anti-diphtheria, anti-tetanus and anti-PRP seroprotected if their anti-diphtheria and anti-tetanus antibody concentration is ≥ 0.1 International Units per milliliter (IU/mL) and if their anti-PRP antibody concentration is ≥ 1 microgram per milliliter (μg/mL), respectively.
Time frame: 31 days following the administration of Infanrix™ and ActHIB
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for those groups receiving Infanrix and ActHIB vaccines.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Havrix Group | Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects | Anti-diphtheria | 89 Participants |
| Havrix Group | Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects | Anti-tetanus | 88 Participants |
| Havrix Group | Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects | Anti-PRP | 90 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects | Anti-diphtheria | 80 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects | Anti-tetanus | 80 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects | Anti-PRP | 77 Participants |
Primary
Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the Second Dose of Havrix
Subjects are defined as being anti-HAV seropositive if their anti-HAV antibody concentration is ≥ 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 cohort for immunogenicity including subjects who had at least one study vaccine administered and for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Havrix Group | Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the Second Dose of Havrix | 88 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the Second Dose of Havrix | 84 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the Second Dose of Havrix | 77 Participants |
Primary
Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN)
Subjects are considered as being vaccine responders if they were initially seronegative and become seropositive (≥ 5 Enzyme Linked Immunosorbent Assay Units per Milliliter (EL.U/mL)), or were initially seropositive and have a 2-fold increase above pre-study concentrations.
Time frame: 31 days following the administration of Infanrix™ and ActHIB
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for those groups receiving Infanrix and ActHIB vaccines.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Havrix Group | Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN) | Anti-PT | 87 Participants |
| Havrix Group | Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN) | Anti-FHA | 85 Participants |
| Havrix Group | Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN) | Anti-PRN | 86 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN) | Anti-PT | 71 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN) | Anti-FHA | 75 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN) | Anti-PRN | 74 Participants |
Secondary
Anti-diphtheria and Anti-tetanus Antibody Geometric Mean Concentrations (GMC)
GMCs are expressed as International Units per milliliter (IU/mL).
Time frame: 31 days following the administration of Infanrix™ and ActHIB
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for those groups receiving Infanrix and ActHIB vaccines.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Havrix Group | Anti-diphtheria and Anti-tetanus Antibody Geometric Mean Concentrations (GMC) | Anti-diphtheria | 11.3 IU/mL |
| Havrix Group | Anti-diphtheria and Anti-tetanus Antibody Geometric Mean Concentrations (GMC) | Anti-tetanus | 7.0 IU/mL |
| Havrix + Infanrix + ActHIB Group | Anti-diphtheria and Anti-tetanus Antibody Geometric Mean Concentrations (GMC) | Anti-diphtheria | 10.3 IU/mL |
| Havrix + Infanrix + ActHIB Group | Anti-diphtheria and Anti-tetanus Antibody Geometric Mean Concentrations (GMC) | Anti-tetanus | 7.3 IU/mL |
Secondary
Anti-hepatitis A Virus (HAV) Antibody Geometric Mean Concentrations (GMC) Following the First Dose of Havrix
Anti-hepatitis A (HAV) antibody geometric mean concentrations (GMC) are expressed as milli-International Units per milliliter (mIU/mL).
Time frame: 31 days following the first dose of Havrix™
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for the Havrix Group and the Havrix + Infanrix + ActHIB Group.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Havrix Group | Anti-hepatitis A Virus (HAV) Antibody Geometric Mean Concentrations (GMC) Following the First Dose of Havrix | 51.5 mIU/mL |
| Havrix + Infanrix + ActHIB Group | Anti-hepatitis A Virus (HAV) Antibody Geometric Mean Concentrations (GMC) Following the First Dose of Havrix | 51.5 mIU/mL |
Secondary
Anti-hepatitis Virus A (HAV) Antibody Geometric Mean Concentrations (GMC) Following the Second Dose of Havrix
Anti-hepatitis A (HAV) antibody geometric mean concentrations (GMC) are 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 cohort for immunogenicity.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Havrix Group | Anti-hepatitis Virus A (HAV) Antibody Geometric Mean Concentrations (GMC) Following the Second Dose of Havrix | 1700.4 mIU/mL |
| Havrix + Infanrix + ActHIB Group | Anti-hepatitis Virus A (HAV) Antibody Geometric Mean Concentrations (GMC) Following the Second Dose of Havrix | 1904.4 mIU/mL |
| Infanrix + ActHIB→Havrix Group | Anti-hepatitis Virus A (HAV) Antibody Geometric Mean Concentrations (GMC) Following the Second Dose of Havrix | 1625.1 mIU/mL |
Secondary
Anti-polyribosylribitol Phosphate (PRP) Antibody Geometric Mean Concentrations (GMC)
GMCs are expressed as microgram/milliliter (µg/mL).
Time frame: 31 days following the administration of Infanrix™ and ActHIB
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for those groups receiving Infanrix and ActHIB vaccines.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Havrix Group | Anti-polyribosylribitol Phosphate (PRP) Antibody Geometric Mean Concentrations (GMC) | 60.8 µg/mL |
| Havrix + Infanrix + ActHIB Group | Anti-polyribosylribitol Phosphate (PRP) Antibody Geometric Mean Concentrations (GMC) | 41.0 µg/mL |
Secondary
Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the First Dose of Havrix
Subjects are defined as being anti-HAV seropositive if their anti-HAV antibody concentration is ≥ 15 milli-International Units per milliliter (mIU/mL).
Time frame: 31 days following the first dose of Havrix™
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for the Havrix Group and the Havrix + Infanrix + ActHIB Group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Havrix Group | Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the First Dose of Havrix | 82 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the First Dose of Havrix | 77 Participants |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events
Since the related information about medically significant events was not specifically collected and new chronic illnesses were only collected in the extended safety follow-up phase, all unsolicited adverse events (AEs) throughout the study are reported in the table without identifying which event was a medically significant or new chronic illness.
Time frame: Active Phase and the 6-months Extended Safety Follow-up (ESFU) Phase.
Population: The analyses were performed on the Total Vaccinated Cohort for the active phase of the study and on the Extended safety follow-up cohort for the 6-month extended follow-up (ESFU) phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Havrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | AEs during Active Phase | 80 Participants |
| Havrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | SAEs | 5 Participants |
| Havrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | AEs during ESFU | 11 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | AEs during Active Phase | 74 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | SAEs | 2 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | AEs during ESFU | 10 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | SAEs | 4 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | AEs during ESFU | 7 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | AEs during Active Phase | 72 Participants |
Secondary
Number of Subjects Reporting Solicited General Adverse Events (AEs)
Solicited general AEs assessed include drowsiness, axillary fever ≥ 37.5°C, irritability and loss of appetite. Data across doses are presented in the table.
Time frame: 4-day period following each dose of study vaccine(s)
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Havrix Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Drowsiness | 44 Participants |
| Havrix Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Fever | 16 Participants |
| Havrix Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Irritability | 56 Participants |
| Havrix Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Loss of appetite | 33 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Loss of appetite | 40 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Drowsiness | 50 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Irritability | 62 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Fever | 26 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Loss of appetite | 48 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Fever | 31 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Irritability | 70 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Solicited General Adverse Events (AEs) | Drowsiness | 53 Participants |
Secondary
Number of Subjects Reporting Solicited Local Adverse Events (AEs)
Solicited local AEs assessed include pain, redness and swelling. Data across doses are presented in the table.
Time frame: 4-day period following each dose of study vaccine(s)
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Havrix Group | Number of Subjects Reporting Solicited Local Adverse Events (AEs) | Redness | 34 Participants |
| Havrix Group | Number of Subjects Reporting Solicited Local Adverse Events (AEs) | Pain | 44 Participants |
| Havrix Group | Number of Subjects Reporting Solicited Local Adverse Events (AEs) | Swelling | 21 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Solicited Local Adverse Events (AEs) | Redness | 54 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Solicited Local Adverse Events (AEs) | Pain | 60 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Solicited Local Adverse Events (AEs) | Swelling | 38 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Solicited Local Adverse Events (AEs) | Pain | 70 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Solicited Local Adverse Events (AEs) | Swelling | 46 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Solicited Local Adverse Events (AEs) | Redness | 63 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
An Adverse Event is 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.
Time frame: 31-day period following each dose of study vaccine(s)
Population: The analysis was performed on the Total Vaccinated Cohort
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Havrix Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 75 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 69 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 71 Participants |
Secondary
Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP)
Seropositivity is defined as antibody concentrations ≥ 5 Enzyme Linked Immunosorbent Assay Units per Milliliter (EL.U/mL) for anti-PT, anti-FHA and anti-PRN antibodies and as antibody concentrations ≥ 0.15 microgram/milliliter (µg/mL) for anti-PRP antibodies.
Time frame: 31 days following the administration of Infanrix™ and ActHIB
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for those groups receiving Infanrix and ActHIB vaccines.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Havrix Group | Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) | Anti-PT | 89 Participants |
| Havrix Group | Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) | Anti-FHA | 89 Participants |
| Havrix Group | Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) | Anti-PRN | 89 Participants |
| Havrix Group | Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) | Anti-PRP | 90 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) | Anti-PRP | 79 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) | Anti-PT | 80 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) | Anti-PRN | 80 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) | Anti-FHA | 80 Participants |
Secondary
Number of Subjects With Vaccine Response to Havrix™.
Vaccine response to Havrix is defined as post-vaccination anti-HAV antibody concentrations ≥ 15 mIU/mL in initially seronegative subjects or a ≥ 2-fold increase above the pre-vaccination anti-HAV antibody concentration in initially seropositive subjects.
Time frame: 31 days following the second dose
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Havrix Group | Number of Subjects With Vaccine Response to Havrix™. | 86 Participants |
| Havrix + Infanrix + ActHIB Group | Number of Subjects With Vaccine Response to Havrix™. | 83 Participants |
| Infanrix + ActHIB→Havrix Group | Number of Subjects With Vaccine Response to Havrix™. | 74 Participants |