Immunogenicity and Safety of Havrix™ Co-Administered With a Diphtheria, Tetanus and Pertussis and a Haemophilus b Vaccine in Children Aged 15 Months

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00197236
• Collaborator: (none)
• Enrollment: 468
• Locations: 22
• Arms: 3
• Duration (Months): 48.7
• Patients Per Site: 21.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis A	Biological: Havrix™; Biological: Infanrix™; Biological: ActHIB™	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 468 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of GSK Biologicals' Inactivated Hepatitis A Vaccine (Havrix™) Co-administered With GSK Biologicals' DTaP Vaccine (Infanrix™) and Aventis Pasteur's Haemophilus b Conjugate Vaccine (ActHIB) in Healthy Children 15 Months of Age
• Study Start Date: Nov 11, 2003
• Actual Primary Completion Date: Dec 3, 2007
• Actual Study Completion Date: Dec 3, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Havrix Group Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	Biological: Havrix™; 2 intramuscular injections, 6 months apart
Experimental: 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.	Biological: Havrix™; 2 intramuscular injections, 6 months apart; Biological: Infanrix™; 1 intramuscular injection; Biological: ActHIB™; 1 intramuscular injection
Active Comparator: 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.	Biological: Havrix™; 2 intramuscular injections, 6 months apart; Biological: Infanrix™; 1 intramuscular injection; Biological: ActHIB™; 1 intramuscular injection

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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.

3. 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 Outcome Measures

1. 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).

2. 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).

3. 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.

4. 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).

5. 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).

6. 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).

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 13 Months
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Phoenix	Arizona	United States	85029
2	GSK Investigational Site	Oakland	California	United States	94612
3	GSK Investigational Site	San Ramon	California	United States	94583
4	GSK Investigational Site	Wilmington	Delaware	United States	19810
5	GSK Investigational Site	Pembroke Pines	Florida	United States	33027
6	GSK Investigational Site	Martinez	Georgia	United States	30907
7	GSK Investigational Site	Waterloo	Iowa	United States	50702
8	GSK Investigational Site	Bossier City	Louisiana	United States	71111
9	GSK Investigational Site	Long Branch	New Jersey	United States	07740
10	GSK Investigational Site	Ithaca	New York	United States	14850
11	GSK Investigational Site	Bismarck	North Dakota	United States	58501
12	GSK Investigational Site	Youngstown	Ohio	United States	44501
13	GSK Investigational Site	Bellevue	Pennsylvania	United States	15202
14	GSK Investigational Site	Hershey	Pennsylvania	United States	17033
15	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15213
16	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15241
17	GSK Investigational Site	Charleston	South Carolina	United States	29425
18	GSK Investigational Site	Beaumont	Texas	United States	77701
19	GSK Investigational Site	Dallas	Texas	United States	75235
20	GSK Investigational Site	Danville	Virginia	United States	24549
21	GSK Investigational Site	Mechanicsville	Virginia	United States	23111
22	GSK Investigational Site	La Crosse	Wisconsin	United States	54601

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Trofa AF, Klein NP, Paul IM, Michaels MG, Goessler M, Chandrasekaran V, Blatter M. Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age. Pediatr Infect Dis J. 2011 Sep;30(9):e164-9. doi: 10.1097/INF.0b013e31821b8a7d.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00197236
• Other Study ID Numbers: 208109/232
• First Posted: Sep 20, 2005
• Last Update Posted: Aug 20, 2018
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Hepatitis A
• Additional relevant MeSH terms: Hepatitis A; Hepatitis

Study Results

Participant Flow

Pre-assignment Detail	Of the total of 468 subjects enrolled, only 394 were vaccinated and as such considered as 'started'.

Arm/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.
Period Title: Overall Study
STARTED	135	127	132
COMPLETED	121	110	109
NOT COMPLETED	14	17	23

Baseline Characteristics

Arm/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group	Total
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.	Total of all reporting groups
Overall Participants	135	127	132	394
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	15.1 (0.36)	15.1 (0.3)	15.0 (0.21)	15.1 (0.30)
Sex: Female, Male (Count of Participants)
Female	55 40.7%	64 50.4%	67 50.8%	186 47.2%
Male	80 59.3%	63 49.6%	65 49.2%	208 52.8%

Outcome Measures

1. Primary Outcome

Title	Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the Second Dose of Havrix
Description	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™

Outcome Measure Data

Analysis Population Description

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/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.
Measure Participants	88	84	77
Count of Participants [Participants]	88 65.2%	84 66.1%	77 58.3%

2. Primary Outcome

Title	Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for those groups receiving Infanrix and ActHIB vaccines.

Arm/Group Title	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group	Havrix Group
Arm/Group Description	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.	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.	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.
Measure Participants	90	80	0
Anti-diphtheria	89 65.9%	80 63%
Anti-tetanus	88 65.2%	80 63%
Anti-PRP	90 66.7%	77 60.6%

3. Primary Outcome

Title	Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN)
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for those groups receiving Infanrix and ActHIB vaccines.

Arm/Group Title	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group	Havrix Group
Arm/Group Description	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.	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.	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.
Measure Participants	88	76	0
Anti-PT	87 64.4%	71 55.9%
Anti-FHA	85 63%	75 59.1%
Anti-PRN	86 63.7%	74 58.3%

4. Secondary Outcome

Title	Anti-diphtheria and Anti-tetanus Antibody Geometric Mean Concentrations (GMC)
Description	GMCs are expressed as International Units per milliliter (IU/mL).
Time Frame	31 days following the administration of Infanrix™ and ActHIB

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for those groups receiving Infanrix and ActHIB vaccines.

Arm/Group Title	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group	Havrix Group
Arm/Group Description	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.	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.	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.
Measure Participants	89	80	0
Anti-diphtheria	11.3	10.3
Anti-tetanus	7.0	7.3

5. Secondary Outcome

Title	Anti-polyribosylribitol Phosphate (PRP) Antibody Geometric Mean Concentrations (GMC)
Description	GMCs are expressed as microgram/milliliter (µg/mL).
Time Frame	31 days following the administration of Infanrix™ and ActHIB

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for those groups receiving Infanrix and ActHIB vaccines.

Arm/Group Title	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group	Havrix Group
Arm/Group Description	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.	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.	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.
Measure Participants	90	79	0
Geometric Mean (95% Confidence Interval) [µg/mL]	60.8	41.0

6. Secondary Outcome

Title	Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP)
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for those groups receiving Infanrix and ActHIB vaccines.

Arm/Group Title	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group	Havrix Group
Arm/Group Description	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.	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.	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.
Measure Participants	90	80	0
Anti-PT	89 65.9%	80 63%
Anti-FHA	89 65.9%	80 63%
Anti-PRN	89 65.9%	80 63%
Anti-PRP	90 66.7%	79 62.2%

7. Secondary Outcome

Title	Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the First Dose of Havrix
Description	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™

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for the Havrix Group and the Havrix + Infanrix + ActHIB Group.

Arm/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.
Measure Participants	94	89	0
Count of Participants [Participants]	82 60.7%	77 60.6%

8. Secondary Outcome

Title	Anti-hepatitis A Virus (HAV) Antibody Geometric Mean Concentrations (GMC) Following the First Dose of Havrix
Description	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™

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol cohort for immunogenicity, only for the Havrix Group and the Havrix + Infanrix + ActHIB Group.

Arm/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.
Measure Participants	94	89	0
Geometric Mean (95% Confidence Interval) [mIU/mL]	51.5	51.5

9. Secondary Outcome

Title	Anti-hepatitis Virus A (HAV) Antibody Geometric Mean Concentrations (GMC) Following the Second Dose of Havrix
Description	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™

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol cohort for immunogenicity.

Arm/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.
Measure Participants	88	84	77
Geometric Mean (95% Confidence Interval) [mIU/mL]	1700.4	1904.4	1625.1

10. Secondary Outcome

Title	Number of Subjects With Vaccine Response to Havrix™.
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol cohort for immunogenicity

Arm/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.
Measure Participants	86	83	74
Count of Participants [Participants]	86 63.7%	83 65.4%	74 56.1%

11. Secondary Outcome

Title	Number of Subjects Reporting Solicited Local Adverse Events (AEs)
Description	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)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.
Measure Participants	130	118	122
Pain	44 32.6%	60 47.2%	70 53%
Redness	34 25.2%	54 42.5%	63 47.7%
Swelling	21 15.6%	38 29.9%	46 34.8%

12. Secondary Outcome

Title	Number of Subjects Reporting Solicited General Adverse Events (AEs)
Description	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)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.
Measure Participants	130	118	123
Drowsiness	44 32.6%	50 39.4%	53 40.2%
Fever	16 11.9%	26 20.5%	31 23.5%
Irritability	56 41.5%	62 48.8%	70 53%
Loss of appetite	33 24.4%	40 31.5%	48 36.4%

13. Secondary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Description	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)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort

Arm/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.
Measure Participants	135	127	132
Count of Participants [Participants]	75 55.6%	69 54.3%	71 53.8%

14. Secondary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Havrix Group	Havrix + Infanrix + ActHIB Group	Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.	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.	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.
Measure Participants	135	127	132
SAEs	5 3.7%	2 1.6%	4 3%
AEs during Active Phase	80 59.3%	74 58.3%	72 54.5%
AEs during ESFU	11 8.1%	10 7.9%	7 5.3%

Adverse Events

Arm/Group Title	Havrix Group		Havrix + Infanrix + ActHIB Group		Infanrix + ActHIB→Havrix Group
Arm/Group Description	Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.		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.		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.
All Cause Mortality
	Havrix Group		Havrix + Infanrix + ActHIB Group		Infanrix + ActHIB→Havrix Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Havrix Group		Havrix + Infanrix + ActHIB Group		Infanrix + ActHIB→Havrix Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/ (NaN)		2/ (NaN)		4/ (NaN)
Cardiac disorders
Tachycardia	0/135 (0%)		1/127 (0.8%)		0/132 (0%)
General disorders
Developmental delay	1/135 (0.7%)		0/127 (0%)		1/132 (0.8%)
Pyrexia	0/135 (0%)		1/127 (0.8%)		0/132 (0%)
Infections and infestations
Gastroenteritis	1/135 (0.7%)		1/127 (0.8%)		0/132 (0%)
Arthritis bacterial	1/135 (0.7%)		0/127 (0%)		0/132 (0%)
Metabolism and nutrition disorders
Dehydration	2/135 (1.5%)		0/127 (0%)		1/132 (0.8%)
Failure to thrive	1/135 (0.7%)		0/127 (0%)		0/132 (0%)
Psychiatric disorders
Expressive language disorder	1/135 (0.7%)		0/127 (0%)		1/132 (0.8%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/135 (0.7%)		0/127 (0%)		0/132 (0%)
Bronchial hyperreactivity	0/135 (0%)		0/127 (0%)		1/132 (0.8%)
Respiratory distress	0/135 (0%)		0/127 (0%)		1/132 (0.8%)
Tonsillar hypertrophy	0/135 (0%)		0/127 (0%)		1/132 (0.8%)
Other (Not Including Serious) Adverse Events
	Havrix Group		Havrix + Infanrix + ActHIB Group		Infanrix + ActHIB→Havrix Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	95/135 (70.4%)		105/127 (82.7%)		107/132 (81.1%)
Gastrointestinal disorders
Diarrhea	9/135 (6.7%)		4/127 (3.1%)		7/132 (5.3%)
Teething	3/135 (2.2%)		8/127 (6.3%)		4/132 (3%)
Vomiting	7/135 (5.2%)		4/127 (3.1%)		4/132 (3%)
General disorders
Pyrexia	9/135 (6.7%)		7/127 (5.5%)		9/132 (6.8%)
Pain at the injection site	44/135 (32.6%)		60/127 (47.2%)		70/132 (53%)
Redness at the injection site	34/135 (25.2%)		54/127 (42.5%)		63/132 (47.7%)
Swelling at the injection site	21/135 (15.6%)		38/127 (29.9%)		46/132 (34.8%)
Drowsiness	44/135 (32.6%)		50/127 (39.4%)		53/132 (40.2%)
Fever	16/135 (11.9%)		26/127 (20.5%)		31/132 (23.5%)
Irritability	56/135 (41.5%)		62/127 (48.8%)		70/132 (53%)
Loss of appetite	33/135 (24.4%)		40/127 (31.5%)		48/132 (36.4%)
Infections and infestations
Otitis media	13/135 (9.6%)		11/127 (8.7%)		22/132 (16.7%)
Upper respiratory tract infection	18/135 (13.3%)		18/127 (14.2%)		16/132 (12.1%)
Viral infection	3/135 (2.2%)		7/127 (5.5%)		3/132 (2.3%)
Respiratory, thoracic and mediastinal disorders
Cough	8/135 (5.9%)		4/127 (3.1%)		14/132 (10.6%)
Rhinorrhea	5/135 (3.7%)		4/127 (3.1%)		14/132 (10.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.