Evaluation of the Immunogenicity, Safety and Reactogenicity of the Combined DTPa-IPV Vaccine in Healthy Infants

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00290342
• Collaborator: (none)
• Enrollment: 458
• Locations: 9
• Arms: 2
• Duration (Months): 12.7
• Patients Per Site: 50.9
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

DTPa and IPV vaccines are recommended for immunization of infants in Korea. The use of combination vaccines simplifies routine paediatric vaccination. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Condition or Disease	Intervention/Treatment	Phase
Tetanus; Acellular Pertussis; Diphtheria	Biological: DTPa-IPV; Biological: DTPa; Biological: IMOVAX Polio®	Phase 3

Detailed Description

Participants in this Phase IIIb study will either receive GSK Biologicals' combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus (DTPa-IPV) vaccine or co-administration of GSK Biologicals' combined diphtheria-tetanus-acellular pertussis (DTPa) vaccine and Sanofi-Pasteurs' inactivated poliovirus vaccine. Vaccines for both groups will be administered at 2, 4 and 6 months of age. Two blood samples will be collected during the course of the study: prior to vaccination and one month after the third vaccine dose.

Study Design

• Study Type: Interventional
• Actual Enrollment: 458 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Multicentric Study to Compare the Immunogenicity, Safety & Reactogenicity of GSK Biologicals' DTPa-IPV Vaccine vs. Co-administration of GSK's DTPa Vaccine & Sanofi-Pasteurs' IPV Vaccine at Different Injection Sites, to Healthy Children
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Jan 1, 2007
• Actual Study Completion Date: Jan 23, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Infanrix-IPV Group Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Biological: DTPa-IPV; 3 intramuscular injections; Other Names: Infanrix™-IPV
Active Comparator: Infanrix + IMOVAX Polio Group Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.	Biological: DTPa; 3 intramuscular injections; Other Names: Infanrix™ ; Biological: IMOVAX Polio®; 3 intramuscular injections

Outcome Measures

Primary Outcome Measures

1. Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) [One month (Month 5) post-primary vaccination course]

   A seroprotected subject was defined as a vaccinated subject with anti-diphteria (anti-D) and anti-tetanus (anti-T) antibody concentrations greater than or equal to (≥) the cut-off value of 0.1 international units/milliliter (IU//mL).

2. Number of Seroprotected Subjects Against Poliovirus (Anti-polio) Types 1, 2 and 3 [One month (Month 5) post-primary vaccination course]

   A seroprotected subject was defined as a vaccinated subject with anti-poliovirus types 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody titers greater than or equal to (≥) the cut-off value of 8.

3. Number of Subjects With a Vaccine Response for Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Haemagglutinin (Anti-FHA) [One month (Month 5) post-primary vaccination course]

   Vaccine response was defined as: - for initially seronegative subjects, antibody concentrations ≥ 5 EL.U/mL one month after third vaccine dose; - for initially seropositive subjects, at least maintenance of pre-vaccination antibody concentrations one month after third vaccine dose.

4. Number of Subjects With Vaccine Response to Pertussis Toxoid (PT), Pertactin (PRN) and Filamentous Haemagglutinin (FHA) Antigens [One month (Month 5) post-primary vaccination course]

   Vaccine response to pertussis toxoid (PT), pertactin (PRN) and filamentous haemagglutinin (FHA) was defined as the appearance of antibodies in subjects who were initially (i.e. before vaccination) seronegative (i.e. with concentrations < 5 EL.U/mL), or at least as the maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e. with concentrations ≥ 5 EL.U/mL value).

Secondary Outcome Measures

1. Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) [Before (Pre) and one month after (Post) the primary vaccination course]

   A seroprotected subject was defined as a vaccinated subject with anti-diphteria (anti-D) and anti-tetanus (anti-T) antibody concentrations greater than or equal to (≥) the cut-off value of 1 international units/milliliter (IU//mL).

2. Concentration of Antibodies Against Diphteria (Anti-D) and Tetanus (Anti-T) [Before (Pre) and one month after (Post) the primary vaccination course]

   Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per millilitre (mIU/mL).

3. Titers for Poliovirus Type 1, 2 and 3 Antibodies [Before (Pre) and one month after (Post) the primary vaccination course]

   Titers for anti-polio 1, 2 and 3 are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was greater than or equal to (≥) 8.

4. Concentrations of Antibodies Against Pertussis Toxoid (Anti-PT), Pertactin (Anti-PRN) and Filamentous Haemagglutinin (Anti-FHA) [Before (Pre) and one month after (Post) the primary vaccination course]

   Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EL.U/mL).

5. Number of Subjects Reporting Solicited Local Symptoms [During the 4-day (Days 0-3) post-vaccination period, across doses]

   Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = crying when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.

6. Number of Subjects Reporting Solicited General Symptoms [During the 4-day (Days 0-3) post-vaccination period, across doses]

   Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 Loss of appetite = not eating at all. Related = symptom symptoms considered by the investigator to have a causal relationship to vaccination.

7. Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) [During the 31-day (Days 0-30) post-vaccination period]

   An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

8. Number of Subjects Reporting Any Serious Adverse Events (SAEs) [During the entire study period (from Month 0 up to Month 5)]

   Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Weeks to 12 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol .

• A male or female between, and including, 8 and 12 weeks (56-90 days) of age at the time of the first vaccination.

• Written informed consent obtained from the parent or guardian of the subject.

• Healthy subjects as established by medical history and clinical examination before entering into the study.

• Born after a gestation period of 36 to 42 weeks inclusive.

Exclusion criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.

• Administration of any vaccine within 30 days (i.e.30 days to 1 day) before the first dose of the study vaccine.

• Planned administration/ administration of a vaccine not foreseen by the study protocol during the study period (i.e. Day 0 to Month 7), with the exception of Bacille Calmette-Guérin (BCG) vaccine, hepatitis B vaccine, pneumococcal vaccine, flu vaccine and Hib vaccine.

• Planned administration/ administration of a vaccine foreseen by the study protocol (i.e. BCG vaccine, hepatitis B vaccine, pneumococcal, flu vaccine and Hib vaccine) during the period 30 days before and one week after the study vaccine dose.

• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).

• Previous vaccination against diphtheria, tetanus, pertussis and/or poliovirus disease.

• History of diphtheria, tetanus, pertussis and/or poliovirus diseases.

• Known exposure to diphtheria, tetanus, pertussis and/or poliovirus before the study period.

• Any anaemia/ thrombocytopenia or blood clot that leads to prohibition from intramuscular injection.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).

• A family history of congenital or hereditary immunodeficiency.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).

• Major congenital defects or serious chronic illness.

• History of any neurologic disorders or seizures.

• Acute disease at the time of enrolment

• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Bucheon-si,		Korea, Republic of	420-767
2	GSK Investigational Site	Daegu		Korea, Republic of	700-712
3	GSK Investigational Site	Gwangju		Korea, Republic of
4	GSK Investigational Site	Incheon		Korea, Republic of	400-711
5	GSK Investigational Site	Jeonju		Korea, Republic of	561-712
6	GSK Investigational Site	Seoul		Korea, Republic of	130-702
7	GSK Investigational Site	Seoul		Korea, Republic of	139-707
8	GSK Investigational Site	Seoul		Korea, Republic of	150-719
9	GSK Investigational Site	Seoul		Korea, Republic of

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

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00290342
• Other Study ID Numbers: 104871
• First Posted: Feb 13, 2006
• Last Update Posted: Oct 29, 2018
• Last Verified: Feb 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Diphtheria; Edetic Acid; Pentetic Acid

Study Results

Participant Flow

Pre-assignment Detail	Of the 458 subjects enrolled in the study, 6 subjects (5 from Infanrix-IPV Group and 1 from Infanrix + IMOVAX Polio Group) were not administered the study vaccine due to consent withdrawal from parents/guardians and received an elimination code.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Period Title: Overall Study
STARTED	224	228
COMPLETED	217	223
NOT COMPLETED	7	5

Baseline Characteristics

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group	Total
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.	Total of all reporting groups
Overall Participants	224	228	452
Age (Weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Weeks]	8.8 (0.9)	8.8 (0.91)	8.8 (0.63)
Sex: Female, Male (Count of Participants)
Female	112 50%	110 48.2%	222 49.1%
Male	112 50%	118 51.8%	230 50.9%

Outcome Measures

1. Primary Outcome

Title	Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T)
Description	A seroprotected subject was defined as a vaccinated subject with anti-diphteria (anti-D) and anti-tetanus (anti-T) antibody concentrations greater than or equal to (≥) the cut-off value of 0.1 international units/milliliter (IU//mL).
Time Frame	One month (Month 5) post-primary vaccination course

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	204	211
Anti-D	204	211
Anti-T	204	211

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV Group, Infanrix + IMOVAX Polio Group
	Comments	Non-inferiority in terms of vaccine response to diphteria
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	To assess the non-inferiority of the Infanrix-IPV Group compared to the Infanrix + IMOVAX Polio Group in terms of vaccine response to diphtheria, standardized asymptotic 95% CI for the groups'difference (Infanrix-IPV Group minus Infanrix + IMOVAX Polio Group) was computed. Objective of non-inferiority was met since the LL of the 95% CI was above -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -1.85 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV Group, Infanrix + IMOVAX Polio Group
	Comments	Non-inferiority in terms of vaccine response to tetanus
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	To assess the non-inferiority of the Infanrix-IPV Group compared to the Infanrix + IMOVAX Polio Group in terms of vaccine response to tetanus, standardized asymptotic 95% CI for the groups'difference (Infanrix-IPV Group minus Infanrix + IMOVAX Polio Group) was computed. Objective of non-inferiority was met since the LL of the 95% CI was above -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -1.85 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Seroprotected Subjects Against Poliovirus (Anti-polio) Types 1, 2 and 3
Description	A seroprotected subject was defined as a vaccinated subject with anti-poliovirus types 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody titers greater than or equal to (≥) the cut-off value of 8.
Time Frame	One month (Month 5) post-primary vaccination course

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	204	207
Anti-polio 1 (N=204; 207)	204	207
Anti-polio 2 (N=204; 205)	204	204
Anti-polio 3 (N=204; 207)	203	206

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV Group, Infanrix + IMOVAX Polio Group
	Comments	Immune response non-inferiority - Anti-Polio 1
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	To assess the non-inferiority of the Infanrix-IPV Group compared to the Infanrix + IMOVAX Polio Group in terms of vaccine response to poliovirus type 1, standardized asymptotic 95% CI for the groups' difference (Infanrix-IPV Group minus Infanrix + IMOVAX Polio Group) was computed. Objective of non-inferiority was met since the LL of the 95% CI was above -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -1.85 to 1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV Group, Infanrix + IMOVAX Polio Group
	Comments	Immune response non-inferiority - Anti-Polio 2
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	To assess the non-inferiority of the Infanrix-IPV Group compared to the Infanrix + IMOVAX Polio Group in terms of vaccine response to poliovirus type 2, standardized asymptotic 95% CI for the groups' difference (Infanrix-IPV Group minus Infanrix + IMOVAX Polio Group) was computed. Objective of non-inferiority was met since the LL of the 95% CI was above -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; -1.36 to 2.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV Group, Infanrix + IMOVAX Polio Group
	Comments	Immune response non-inferiority - Anti-Polio 3
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	To assess the non-inferiority of the Infanrix-IPV Group compared to the Infanrix + IMOVAX Polio Group in terms of vaccine response to poliovirus type 3, standardized asymptotic 95% CI for the groups' difference (Infanrix-IPV Group minus Infanrix + IMOVAX Polio Group) was computed. Objective of non-inferiority was met since the LL of the 95% CI was above -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -2.28 to 2.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Number of Subjects With a Vaccine Response for Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Haemagglutinin (Anti-FHA)
Description	Vaccine response was defined as: - for initially seronegative subjects, antibody concentrations ≥ 5 EL.U/mL one month after third vaccine dose; - for initially seropositive subjects, at least maintenance of pre-vaccination antibody concentrations one month after third vaccine dose.
Time Frame	One month (Month 5) post-primary vaccination course

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	202	211
Anti-PT	200	206
Anti-FHA	201	209
Anti-PRN	202	210

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV Group, Infanrix + IMOVAX Polio Group
	Comments	Immune response non-inferiority - Anti-PT
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	To assess the non-inferiority of the Infanrix-IPV Group compared to the Infanrix + IMOVAX Polio Group in terms of vaccine response to pertussis toxoid, standardized asymptotic 95% CI for the groups' difference (Infanrix-IPV Group minus Infanrix + IMOVAX Polio Group) was computed. Objective of non-inferiority was met since the LL of the 95% CI was above -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; -0.46 to 4.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV Group, Infanrix + IMOVAX Polio Group
	Comments	Immune response non-inferiority - Anti-FHA
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	To assess the non-inferiority of the Infanrix-IPV Group compared to the Infanrix + IMOVAX Polio Group in terms of vaccine response to filamentous haemagglutinin, standardized asymptotic 95% CI for the groups' difference (Infanrix-IPV Group minus Infanrix + IMOVAX Polio Group) was computed. Objective of non-inferiority was met since the LL of the 95% CI was above -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	0.45
	Confidence Interval	(2-Sided) 95%; -1.88 to 2.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV Group, Infanrix + IMOVAX Polio Group
	Comments	Immune response non-inferiority - Anti-PRN
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	To assess the non-inferiority of the Infanrix-IPV Group compared to the Infanrix + IMOVAX Polio Group in terms of vaccine response to pertactin, standardized asymptotic 95% CI for the groups' difference (Infanrix-IPV Group minus Infanrix + IMOVAX Polio Group) was computed. Objective of non-inferiority was met since the LL of the 95% CI was above -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	0.47
	Confidence Interval	(2-Sided) 95%; -1.4 to 2.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Number of Subjects With Vaccine Response to Pertussis Toxoid (PT), Pertactin (PRN) and Filamentous Haemagglutinin (FHA) Antigens
Description	Vaccine response to pertussis toxoid (PT), pertactin (PRN) and filamentous haemagglutinin (FHA) was defined as the appearance of antibodies in subjects who were initially (i.e. before vaccination) seronegative (i.e. with concentrations < 5 EL.U/mL), or at least as the maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e. with concentrations ≥ 5 EL.U/mL value).
Time Frame	One month (Month 5) post-primary vaccination course

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	202	211
Anti-PT (N=200; 209)	200	206
Anti-FHA (N=202; 211)	201	209
Anti-PRN (N=202; 211)	202	210

5. Secondary Outcome

Title	Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T)
Description	A seroprotected subject was defined as a vaccinated subject with anti-diphteria (anti-D) and anti-tetanus (anti-T) antibody concentrations greater than or equal to (≥) the cut-off value of 1 international units/milliliter (IU//mL).
Time Frame	Before (Pre) and one month after (Post) the primary vaccination course

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	204	212
Anti-D, PRE (N=202; 212)	0	0
Anti-D, POST (N=204; 211)	194	187
Anti-T, PRE (N=202; 212)	1	1
Anti-T, POST (N=204; 211)	204	208

6. Secondary Outcome

Title	Concentration of Antibodies Against Diphteria (Anti-D) and Tetanus (Anti-T)
Description	Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per millilitre (mIU/mL).
Time Frame	Before (Pre) and one month after (Post) the primary vaccination course

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	204	212
Anti-D, PRE (N=202; 212)	0.052	0.053
Anti-D, POST (N=204; 211)	4.333	2.63
Anti-T, PRE (N=202; 212)	0.059	0.06
Anti-T, POST (N=204; 211)	10.306	7.139

7. Secondary Outcome

Title	Titers for Poliovirus Type 1, 2 and 3 Antibodies
Description	Titers for anti-polio 1, 2 and 3 are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was greater than or equal to (≥) 8.
Time Frame	Before (Pre) and one month after (Post) the primary vaccination course

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	204	212
Anti-polio 1, PRE (N=199; 212)	6.3	6.1
Anti-polio 1, POST (N=204; 207)	755.7	263
Anti-polio 2, PRE (N=202; 211)	5.8	6.5
Anti-polio 2, POST (N=204; 205)	704.7	267.6
Anti-polio 3, PRE (N=202; 212)	5	4.9
Anti-polio 3, POST (N=204; 207)	1209.5	438.3

8. Secondary Outcome

Title	Concentrations of Antibodies Against Pertussis Toxoid (Anti-PT), Pertactin (Anti-PRN) and Filamentous Haemagglutinin (Anti-FHA)
Description	Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EL.U/mL).
Time Frame	Before (Pre) and one month after (Post) the primary vaccination course

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	204	212
Anti-PT, PRE (N=200; 210)	3	3.2
Anti-PT, POST (N=204; 211)	63.3	55.6
Anti-FHA, PRE (N=202; 212)	7.4	8.5
Anti-FHA, POST (N=204; 211)	294.3	259.6
Anti-PRN, PRE (N=202; 212)	2.7	2.7
Anti-PRN, POST (N=204; 211)	205	155.6

9. Secondary Outcome

Title	Number of Subjects Reporting Solicited Local Symptoms
Description	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = crying when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Time Frame	During the 4-day (Days 0-3) post-vaccination period, across doses

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 and who had the symptom sheet filled-in.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	220	226
Any Pain	92	96
Grade 3 Pain	5	8
Any Redness	115	116
Grade 3 Redness	22	26
Any Swelling	74	79
Grade 3 Swelling	17	20

10. Secondary Outcome

Title	Number of Subjects Reporting Solicited General Symptoms
Description	Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 Loss of appetite = not eating at all. Related = symptom symptoms considered by the investigator to have a causal relationship to vaccination.
Time Frame	During the 4-day (Days 0-3) post-vaccination period, across doses

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 and who had the symptom sheet filled-in.

Arm/Group Title	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	221	226
Any Drowsiness	95	99
Grade 3 Drowsiness	4	2
Related Drowsiness	54	53
Any Fever (axillary)	63	38
Grade 3 Fever (axillary)	4	1
Related Fever (axillary)	45	22
Any Irritability	140	139
Grade Irritability	14	10
Related Irritability	85	91
Any Loss of appetite	84	78
Grade 3 Loss of appetite	1	0
Related Loss of appetite	50	46

11. Secondary Outcome

Title	Number of Subjects Reporting Any Unsolicited Adverse Events (AEs)
Description	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time Frame	During the 31-day (Days 0-30) post-vaccination period

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	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	224	228
Number [Subjects]	135	138

12. Secondary Outcome

Title	Number of Subjects Reporting Any Serious Adverse Events (SAEs)
Description	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame	During the entire study period (from Month 0 up to Month 5)

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	Infanrix-IPV Group	Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
Measure Participants	224	228
Number [Subjects]	15	17

Adverse Events

Time Frame	Solicited local and general symptoms during the 4-day (Days 0-3) post-vaccination period; Unsolicited AEs during the 31-day (Days 0-30) post-vaccination period and SAEs during the entire study period (from Month 0 up to Month 5)
Arm/Group Title	Infanrix-IPV Group		Infanrix + IMOVAX Polio Group
Arm/Group Description	Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh.		Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs.
All Cause Mortality
	Infanrix-IPV Group		Infanrix + IMOVAX Polio Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Infanrix-IPV Group		Infanrix + IMOVAX Polio Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/224 (6.7%)		17/228 (7.5%)
Congenital, familial and genetic disorders
Patent ductus arteriosus	0/224 (0%)		1/228 (0.4%)
Gastrointestinal disorders
Inguinal hernia	0/224 (0%)		2/228 (0.9%)
General disorders
Pyrexia	2/224 (0.9%)		1/228 (0.4%)
Hepatobiliary disorders
Hepatic function abnormal	1/224 (0.4%)		0/228 (0%)
Infections and infestations
Bronchiolitis	7/224 (3.1%)		3/228 (1.3%)
Pneumonia	4/224 (1.8%)		5/228 (2.2%)
Urinary tract infection	3/224 (1.3%)		5/228 (2.2%)
Gastroenteritis	2/224 (0.9%)		2/228 (0.9%)
Kawasaki's disease	0/224 (0%)		1/228 (0.4%)
Otitis media acute	1/224 (0.4%)		0/228 (0%)
Pyelonephritis acute	1/224 (0.4%)		0/228 (0%)
Sepsis	1/224 (0.4%)		0/228 (0%)
Nervous system disorders
Febrile convulsion	1/224 (0.4%)		0/228 (0%)
Other (Not Including Serious) Adverse Events
	Infanrix-IPV Group		Infanrix + IMOVAX Polio Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	200/224 (89.3%)		196/228 (86%)
Gastrointestinal disorders
Diarrhoea	12/224 (5.4%)	16	8/228 (3.5%)	8
General disorders
Pain	92/224 (41.1%)	164	96/228 (42.1%)	161
Pyrexia	74/224 (33%)	91	40/228 (17.5%)	48
Swelling	74/224 (33%)	114	79/228 (34.6%)	129
Infections and infestations
Bronchiolitis	14/224 (6.3%)	14	7/228 (3.1%)	11
Bronchitis	7/224 (3.1%)	8	12/228 (5.3%)	12
Gastroenteritis	10/224 (4.5%)	11	13/228 (5.7%)	14
Upper respiratory tract infection	72/224 (32.1%)	98	61/228 (26.8%)	88
Metabolism and nutrition disorders
Decreased appetite	84/224 (37.5%)	130	78/228 (34.2%)	115
Nervous system disorders
Somnolence	95/224 (42.4%)	152	99/228 (43.4%)	161
Psychiatric disorders
Irritability	140/224 (62.5%)	238	139/228 (61%)	241
Skin and subcutaneous tissue disorders
Dermatitis atopic	16/224 (7.1%)	18	17/228 (7.5%)	20
Erythema	115/224 (51.3%)	212	116/228 (50.9%)	209

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.