Immunogenicity and Safety Study of GSK Biologicals' Infanrix-IPV+Hib™ Vaccine

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01086423
• Collaborator: (none)
• Enrollment: 985
• Locations: 2
• Arms: 3
• Duration (Months): 8.6
• Patients Per Site: 492.5
• Patients Per Site Per Month: 57

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the immunogenicity and reactogenicity of Infanrix-IPV/Hib™ vaccine when administered to healthy Chinese infants at 2, 3 and 4 or 3, 4 and 5 months of age.

Condition or Disease	Intervention/Treatment	Phase
Tetanus; Poliomyelitis; Acellular Pertussis; Diphtheria; Haemophilus Influenzae Type b	Biological: Infanrix-IPV/Hib™; Biological: Infanrix Hib™; Biological: Poliorix™	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 985 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of GlaxoSmithKline Biologicals' DTPa-IPV/Hib (Infanrix-IPV+Hib™) in Infants
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Nov 19, 2010
• Actual Study Completion Date: Nov 19, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INFANRIX-IPV+HIB 1 GROUP Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix™-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Biological: Infanrix-IPV/Hib™; Intramuscular, three doses
Experimental: INFANRIX-IPV+HIB 2 GROUP Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix™-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Biological: Infanrix-IPV/Hib™; Intramuscular, three doses
Active Comparator: INFANRIX-HIB+POLIORIX GROUP Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix™-Hib vaccine co-administered with Poliorix™ vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.	Biological: Infanrix Hib™; Intramuscular, three doses; Biological: Poliorix™; Intramuscular, three doses

Outcome Measures

Primary Outcome Measures

1. Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Antigens [One month after the third vaccine dose (Month 3 or Month 4)]

   A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations greater than or equal to (≥) 0.1 international units per milliliter (IU/mL).

2. Number of Seroprotected Subjects Against Polyribosyl-ribitol-phosphate (PRP) Antigen [One month after the third vaccine dose (Month 3 or Month 4)]

   A seroprotected subject was defined as a subject with anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (μg/mL).

3. Number of Seroprotected Subjects Against Poliovirus Types 1, 2 and 3 Antigens [One month after the third vaccine dose (Month 3 or Month 4)]

   A seroprotected subject was defined as a subject with anti-poliovirus (anti-polio) types 1, 2 and 3 antibody titres ≥ the value of 8.

4. Number of Subjects With a Vaccine Response to Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens [One month after the third vaccine dose (Month 3 or Month 4)]

   Vaccine response was defined as: For PT and FHA response, antibody concentration ≥ 20 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) at post-vaccination. For PRN response: for initially seronegative subjects [antibody concentration lower than (<) 5 EL.U/mL], post-vaccination antibody concentration ≥ 20 EL.U/mL; for initially seropositive subjects (antibody concentration ≥ 5 EL.U/mL), at least a 4-fold increase in antibody concentration from pre to post-vaccination.

Secondary Outcome Measures

1. Anti-D and Anti-T Antibody Concentrations [Before the first dose (Month 0) and one month after the third dose of vaccination (Month 3 or Month 4)]

   Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL.

2. Anti-PRP Antibody Concentrations [Before the first dose (Month 0) and one month after the third dose of study vaccine (Month 3 or Month 4)]

   Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in µg/mL.

3. Anti-polio Types 1, 2 and 3 Antibody Titers [Before the first dose (Month 0) and one month after the third dose of study vaccine (Month 3 or Month 4)]

   Antibody titers were presented as geometric mean titers (GMTs).

4. Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations [Before (Month 0) and one month after the third dose of study vaccine (Month 3 or Month 4)]

   Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in EL.U/mL.

5. Number of Subjects With Any Solicited Local Symptoms [During the 4-day (Days 0-3) post-vaccination period after each vaccine dose and across doses]

   Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.

6. Number of Subjects With Any Solicited General Symptoms [During the 4-day (Days 0-3) post-vaccination period after each vaccine dose and across doses]

   Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade or relationship to study vaccination.

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

   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 With Serious Adverse Events (SAEs) [During the entire study period (from Month 0 to Month 4/5)]

   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: 60 Days to 90 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• A male or female infant between, and including, 60 and 90 days of age at the time of the first study visit.

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

• Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol.

• Written informed consent obtained from the parent(s) or LAR(s) of the subject.

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

Exclusion Criteria:

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

• Child in care.

• Chronic administration of immunosuppressants or other immune-modifying drugs since birth.

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

• Administration of a vaccine not foreseen by the study protocol within 30 days prior to vaccination, or planned administration during the study period, with the exception of hepatitis B vaccine.

• 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.

• Evidence of previous or intercurrent diphtheria, tetanus, pertussis, poliomyelitis and/or Haemophilus influenzae type b (Hib) disease or vaccination.

• History of seizures or progressive neurological disease.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).

• Major congenital defects or serious chronic illness.

The following condition is temporary or self-limiting and a subject may be vaccinated once the condition has resolved and no other exclusion criteria are met:

• Current febrile illness or axillary temperature > 37.0°C or other moderate to severe illness within 24 hours of study vaccine administration.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Wuzhou	Guangxi	China	543002
2	GSK Investigational Site	Wuzhou	Guangxi	China	543100

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01086423
• Other Study ID Numbers: 112584
• First Posted: Mar 15, 2010
• Last Update Posted: Jun 6, 2018
• Last Verified: Apr 1, 2017

• Keywords provided by GlaxoSmithKline: Infanrix-IPV+Hib
• Additional relevant MeSH terms: Diphtheria; Poliomyelitis

Study Results

Participant Flow

Recruitment Details	Out of the 985 subjects originally enrolled in the study, 984 subjects were vaccinated with at least one dose of the study vaccine.
Pre-assignment Detail	During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Period Title: Overall Study
STARTED	330	324	330
COMPLETED	320	321	321
NOT COMPLETED	10	3	9

Baseline Characteristics

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group	Total
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.	Total of all reporting groups
Overall Participants	330	324	330	984
Age (Weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Weeks]	9.9 (1.12)	14.3 (1.14)	9.9 (1.17)	11.35 (2.36)
Sex: Female, Male (Count of Participants)
Female	155 47%	147 45.4%	141 42.7%	443 45%
Male	175 53%	177 54.6%	189 57.3%	541 55%
Race/Ethnicity, Customized (Count of Participants)
Asian-Chinese heritage	330 100%	324 100%	330 100%	984 100%

Outcome Measures

1. Primary Outcome

Title	Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Antigens
Description	A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations greater than or equal to (≥) 0.1 international units per milliliter (IU/mL).
Time Frame	One month after the third vaccine dose (Month 3 or Month 4)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included a subset of evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one study vaccine antigen component were available.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	147	156	147
Anti-D	146 44.2%	156 48.1%	147 44.5%
Anti-T	147 44.5%	156 48.1%	147 44.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV+Hib 1 Group, Infanrix-Hib+Poliorix Group
	Comments	To demonstrate that the immunogenicity of Infanrix™ -IPV+Hib vaccine administered at 2, 3 and 4 months of age was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age, in terms of immune response to anti-D, one month after the third vaccine dose.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for evaluation of Non-inferiority: The upper limit (UL) of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; -1.88 to 3.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV+Hib 1 Group, Infanrix-Hib+Poliorix Group
	Comments	To demonstrate that the immunogenicity of Infanrix™-IPV+Hib vaccine administered at 2, 3 and 4 months of age was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age, in terms of immune response to anti-T, one month after the third vaccine dose.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for evaluation of Non-inferiority: The UL of the standardized asymptotic 95% CI on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 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%; -2.56 to 2.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Seroprotected Subjects Against Polyribosyl-ribitol-phosphate (PRP) Antigen
Description	A seroprotected subject was defined as a subject with anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (μg/mL).
Time Frame	One month after the third vaccine dose (Month 3 or Month 4)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included a subset of evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one study vaccine antigen component were available.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	147	157	150
Count of Participants [Participants]	142 43%	155 47.8%	133 40.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV+Hib 1 Group, Infanrix-Hib+Poliorix Group
	Comments	To demonstrate that the immunogenicity of Infanrix™-IPV+Hib vaccine administered at 2, 3 and 4 months of age was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age, in terms of immune response to anti-PRP antibodies, one month after the third vaccine dose.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for evaluation of Non-inferiority: The UL of the standardized asymptotic 95% CI on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	-7.93
	Confidence Interval	(2-Sided) 95%; -14.44 to -2.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Number of Seroprotected Subjects Against Poliovirus Types 1, 2 and 3 Antigens
Description	A seroprotected subject was defined as a subject with anti-poliovirus (anti-polio) types 1, 2 and 3 antibody titres ≥ the value of 8.
Time Frame	One month after the third vaccine dose (Month 3 or Month 4)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included a subset of evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one study vaccine antigen component were available.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	147	157	150
Anti-polio 1	147 44.5%	157 48.5%	150 45.5%
Anti-polio 2	147 44.5%	157 48.5%	150 45.5%
Anti-polio 3	147 44.5%	157 48.5%	150 45.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV+Hib 1 Group, Infanrix-Hib+Poliorix Group
	Comments	To demonstrate that the immunogenicity of Infanrix™-IPV+Hib vaccine administered at 2, 3 and 4 months of age was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age, in terms of immune response to anti-Polio type 1 antibodies, one month after the third vaccine dose.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for evaluation of Non-inferiority: The UL of the standardized asymptotic 95% CI on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 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%; -2.51 to 2.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV+Hib 1 Group, Infanrix-Hib+Poliorix Group
	Comments	To demonstrate that the immunogenicity of Infanrix™-IPV+Hib vaccine administered at 2, 3 and 4 months of age was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age, in terms of immune response to anti-Polio type 2 antibodies, one month after the third vaccine dose.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for evaluation of Non-inferiority: The UL of the standardized asymptotic 95% CI on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 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%; -2.51 to 2.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV+Hib 1 Group, Infanrix-Hib+Poliorix Group
	Comments	To demonstrate that the immunogenicity of Infanrix™-IPV+Hib vaccine administered at 2, 3 and 4 months of age was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age, in terms of immune response to anti-Polio type 3 antibodies, one month after the third vaccine dose.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for evaluation of Non-inferiority: The UL of the standardized asymptotic 95% CI on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 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%; -2.51 to 2.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Number of Subjects With a Vaccine Response to Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens
Description	Vaccine response was defined as: For PT and FHA response, antibody concentration ≥ 20 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) at post-vaccination. For PRN response: for initially seronegative subjects [antibody concentration lower than (<) 5 EL.U/mL], post-vaccination antibody concentration ≥ 20 EL.U/mL; for initially seropositive subjects (antibody concentration ≥ 5 EL.U/mL), at least a 4-fold increase in antibody concentration from pre to post-vaccination.
Time Frame	One month after the third vaccine dose (Month 3 or Month 4)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included a subset of evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one study vaccine antigen component were available.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	147	156	148
Anti-PT	147 44.5%	155 47.8%	147 44.5%
Anti-FHA	147 44.5%	155 47.8%	144 43.6%
Anti-PRN	145 43.9%	156 48.1%	145 43.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV+Hib 1 Group, Infanrix-Hib+Poliorix Group
	Comments	To demonstrate that the immunogenicity of Infanrix™-IPV+Hib vaccine administered at 2, 3 and 4 months of age was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age, in terms of immune response to anti-PT antigens, one month after the third vaccine dose.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for evaluation of Non-inferiority: The UL of the standardized asymptotic 95% CI on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 95%; -3.74 to 1.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV+Hib 1 Group, Infanrix-Hib+Poliorix Group
	Comments	To demonstrate that the immunogenicity of Infanrix™-IPV+Hib vaccine administered at 2, 3 and 4 months of age was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age, in terms of immune response to anti-FHA antigens, one month after the third vaccine dose.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for evaluation of Non-inferiority: The UL of the standardized asymptotic 95% CI on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -6.75 to -0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Infanrix-IPV+Hib 1 Group, Infanrix-Hib+Poliorix Group
	Comments	To demonstrate that the immunogenicity of Infanrix™-IPV+Hib vaccine administered at 2, 3 and 4 months of age was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age, in terms of immune response to anti-PRN antigens, one month after the third vaccine dose.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for evaluation of Non-inferiority: The UL of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seroprotection rate
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -4.6 to 3.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Anti-D and Anti-T Antibody Concentrations
Description	Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL.
Time Frame	Before the first dose (Month 0) and one month after the third dose of vaccination (Month 3 or Month 4)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included a subset of evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one study vaccine antigen component were available.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	147	157	151
Anti-D, M0	0.052	0.051	0.051
Anti-D, M3/M4	0.719	0.753	0.613
Anti-T, M0	0.051	0.052	0.05
Anti-T, M3/M4	4.118	4.124	3.618

6. Secondary Outcome

Title	Anti-PRP Antibody Concentrations
Description	Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in µg/mL.
Time Frame	Before the first dose (Month 0) and one month after the third dose of study vaccine (Month 3 or Month 4)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included a subset of evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one study vaccine antigen component were available.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	147	157	151
Anti-PRP, M0	0.127	0.135	0.15
Anti-PRP, M3/M4	5.601	9.396	2.826

7. Secondary Outcome

Title	Anti-polio Types 1, 2 and 3 Antibody Titers
Description	Antibody titers were presented as geometric mean titers (GMTs).
Time Frame	Before the first dose (Month 0) and one month after the third dose of study vaccine (Month 3 or Month 4)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included a subset of evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one study vaccine antigen component were available.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	147	157	151
Anti-polio 1, M0	9.4	7.1	9.2
Anti-polio 1, M3/M4	1143.7	1328.9	533.6
Anti-polio 2, M0	6.3	5	6.9
Anti-polio 2, M3/M4	416.2	458.6	186.4
Anti-polio 3, M0	5.8	4.9	5.7
Anti-polio 3, M3/M4	1478.8	1411.6	820.7

8. Secondary Outcome

Title	Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations
Description	Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in EL.U/mL.
Time Frame	Before (Month 0) and one month after the third dose of study vaccine (Month 3 or Month 4)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included a subset of evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one study vaccine antigen component were available.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	147	157	151
Anti-PT, M0	2.9	2.7	2.8
Anti-PT, M3/M4	108.7	114.7	97.1
Anti-FHA, M0	2.9	2.6	2.9
Anti-FHA, M3/M4	87.7	87.6	76.3
Anti-PRN, M0	2.6	2.6	2.5
Anti-PRN, M3/M4	44.8	43.7	43.2

9. Secondary Outcome

Title	Number of Subjects With Any Solicited Local Symptoms
Description	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.
Time Frame	During the 4-day (Days 0-3) post-vaccination period after each vaccine dose and across doses

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort, which included all subjects with at least one vaccine administration documented, who had their symptom sheets filled in.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	330	324	330
Any Pain, Dose 1	65 19.7%	64 19.8%	83 25.2%
Any Redness, Dose 1	16 4.8%	19 5.9%	15 4.5%
Any Swelling, Dose 1	8 2.4%	9 2.8%	9 2.7%
Any Pain, Dose 2	43 13%	50 15.4%	58 17.6%
Any Redness, Dose 2	14 4.2%	19 5.9%	13 3.9%
Any Swelling, Dose 2	6 1.8%	8 2.5%	8 2.4%
Any Pain, Dose 3	39 11.8%	41 12.7%	39 11.8%
Any Redness, Dose 3	10 3%	11 3.4%	8 2.4%
Any Swelling, Dose 3	5 1.5%	8 2.5%	6 1.8%
Any Pain, Across doses	90 27.3%	91 28.1%	102 30.9%
Any Redness, Across doses	28 8.5%	34 10.5%	26 7.9%
Any Swelling, Across doses	14 4.2%	17 5.2%	19 5.8%

10. Secondary Outcome

Title	Number of Subjects With Any Solicited General Symptoms
Description	Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade or relationship to study vaccination.
Time Frame	During the 4-day (Days 0-3) post-vaccination period after each vaccine dose and across doses

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort, which included all subjects with at least one vaccine administration documented, who had their symptom sheets filled in.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	330	324	330
Any Drowsiness, Dose 1	95 28.8%	80 24.7%	69 20.9%
Any Irritability, Dose 1	123 37.3%	120 37%	116 35.2%
Any Loss of appetite, Dose 1	77 23.3%	86 26.5%	76 23%
Any Fever/Axillary, Dose 1	137 41.5%	152 46.9%	103 31.2%
Any Drowsiness, Dose 2	53 16.1%	47 14.5%	53 16.1%
Any Irritability, Dose 2	96 29.1%	100 30.9%	103 31.2%
Any Loss of appetite, Dose 2	69 20.9%	72 22.2%	59 17.9%
Any Fever/Axillary, Dose 2	131 39.7%	144 44.4%	102 30.9%
Any Drowsiness, Dose 3	43 13%	32 9.9%	28 8.5%
Any Irritability, Dose 3	77 23.3%	70 21.6%	61 18.5%
Any Loss of appetite, Dose 3	65 19.7%	57 17.6%	36 10.9%
Any Fever/Axillary, Dose 3	93 28.2%	82 25.3%	75 22.7%
Any Drowsiness, Across doses	124 37.6%	102 31.5%	99 30%
Any Irritability, Across doses	171 51.8%	166 51.2%	163 49.4%
Any Loss of appetite, Across doses	131 39.7%	136 42%	114 34.5%
Any Fever/Axillary, Across doses	217 65.8%	217 67%	183 55.5%

11. Secondary Outcome

Title	Number of Subjects With 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 after any dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort, which included all subjects with at least one vaccine administration documented.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	330	324	330
Count of Participants [Participants]	98 29.7%	114 35.2%	110 33.3%

12. Secondary Outcome

Title	Number of Subjects With 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 to Month 4/5)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort, which included all subjects with at least one vaccine administration documented.

Arm/Group Title	Infanrix-IPV+Hib 1 Group	Infanrix-IPV+Hib 2 Group	Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
Measure Participants	330	324	330
Count of Participants [Participants]	6 1.8%	3 0.9%	4 1.2%

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. SAEs: during the entire study period (from Month 0 up to Month 4/5).
Arm/Group Title	Infanrix-IPV+Hib 1 Group		Infanrix-IPV+Hib 2 Group		Infanrix-Hib+Poliorix Group
Arm/Group Description	Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.		Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.		Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
All Cause Mortality
	Infanrix-IPV+Hib 1 Group		Infanrix-IPV+Hib 2 Group		Infanrix-Hib+Poliorix Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/330 (0.3%)		0/324 (0%)		0/330 (0%)
Serious Adverse Events
	Infanrix-IPV+Hib 1 Group		Infanrix-IPV+Hib 2 Group		Infanrix-Hib+Poliorix Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/330 (1.8%)		3/324 (0.9%)		4/330 (1.2%)
Gastrointestinal disorders
Enteritis	1/330 (0.3%)		1/324 (0.3%)		0/330 (0%)
Diarrhoea	0/330 (0%)		0/324 (0%)		1/330 (0.3%)
Hepatobiliary disorders
Hepatitis neonatal	0/330 (0%)		1/324 (0.3%)		0/330 (0%)
Infections and infestations
Bronchopneumonia	3/330 (0.9%)		2/324 (0.6%)		1/330 (0.3%)
Bronchitis	2/330 (0.6%)		0/324 (0%)		0/330 (0%)
Pharyngitis	0/330 (0%)		0/324 (0%)		1/330 (0.3%)
Pneumonia	0/330 (0%)		0/324 (0%)		1/330 (0.3%)
Septic shock	1/330 (0.3%)		0/324 (0%)		0/330 (0%)
Metabolism and nutrition disorders
Hypokalaemia	1/330 (0.3%)		0/324 (0%)		0/330 (0%)
Malnutrition	1/330 (0.3%)		0/324 (0%)		0/330 (0%)
Other (Not Including Serious) Adverse Events
	Infanrix-IPV+Hib 1 Group		Infanrix-IPV+Hib 2 Group		Infanrix-Hib+Poliorix Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	279/330 (84.5%)		277/324 (85.5%)		272/330 (82.4%)
Gastrointestinal disorders
Diarrhoea	23/330 (7%)		22/324 (6.8%)		33/330 (10%)
General disorders
Pyrexia	19/330 (5.8%)		24/324 (7.4%)		17/330 (5.2%)
Pain	90/330 (27.3%)		91/324 (28.1%)		102/330 (30.9%)
Redness	28/330 (8.5%)		34/324 (10.5%)		26/330 (7.9%)
Swelling	14/330 (4.2%)		17/324 (5.2%)		19/330 (5.8%)
Drowsiness	124/330 (37.6%)		102/324 (31.5%)		99/330 (30%)
Irritability	171/330 (51.8%)		166/324 (51.2%)		163/330 (49.4%)
Loss of appetite	131/330 (39.7%)		136/324 (42%)		114/330 (34.5%)
Fever (Axillary)	217/330 (65.8%)		217/324 (67%)		183/330 (55.5%)
Nasopharyngitis	42/330 (12.7%)		46/324 (14.2%)		50/330 (15.2%)

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.