Study to Evaluate Antibody Persistence in Children Previously Vaccinated With Infanrix Hexa™ or Infanrix-IPV/Hib™

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01358825
• Collaborator: (none)
• Enrollment: 58
• Locations: 4
• Arms: 2
• Actual Duration (Months): 1.5
• Patients Per Site: 14.5
• Patients Per Site Per Month: 9.6

Study Details

Study Description

Brief Summary

The aim of this study is to assess antibody persistence in infants who received three doses of Infanrix hexa™ (DTPa-HBV-IPV/Hib) or Infanrix-IPV/Hib™ (DTPa-IPV/Hib) at 3, 5 and 11 months of age in study NCT00307034.

Condition or Disease	Intervention/Treatment	Phase
Tetanus; Poliomyelitis; Haemophilus Influenzae Type b; Acellular Pertussis; Diphtheria; Hepatitis B; Diphtheria-Tetanus-aPertussis-Poliomyelitis-Haemophilus Influenzae Type b Vaccines	Procedure: Blood Sampling	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Antibody Persistence in Children Previously Vaccinated With Three Doses of Infanrix Hexa™ or Infanrix-IPV/Hib™
• Actual Study Start Date: May 30, 2011
• Actual Primary Completion Date: Jul 15, 2011
• Actual Study Completion Date: Jul 15, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Infanrix hexa Group Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (DTPa-HBV-IPV/Hib) administered intramuscularly in study NCT00307034.	Procedure: Blood Sampling; A blood sample will be taken at 5 years of age, after vaccination in the primary study.
Experimental: Infanrix-IPV/Hib Group Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (DTPa-IPV/Hib) administered intramuscularly in study NCT00307034.	Procedure: Blood Sampling; A blood sample will be taken at 5 years of age, after vaccination in the primary study.

Outcome Measures

Primary Outcome Measures

1. Number of Seroprotected Subjects Against Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T). [At Day 0]

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

2. Concentrations of Antibodies Against Anti-D and Anti-T [At Day 0]

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

3. Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Antifilamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations ≥5 ELISA Units Per Milliliter (EL.U/mL). [At Day 0]

   Cut-off values assessed were greater than or equal to 5 ELISA units per millilitre (EL.U/mL) in the sera of subjects seronegative before vaccination.

4. Concentrations of Antibodies Against Anti-PT, Anti-FHA and Anti-PRN. [At Day 0]

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

5. Number of Seroprotected Subjects Against Anti-hepatitis B Surface Antigen (Anti-HBs). [At Day 0]

   Seroprotection = anti-HBs antibody concentration ≥ 10 milli-international units per milliliter (mIU/mL).

6. Concentrations of Antibodies Against Anti-HBs. [At Day 0]

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

7. Number of Seroprotected Subjects Against Anti-polyribosyl Ribitol Phosphate (Anti-PRP). [At Day 0]

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

8. Concentrations of Antibodies Against Anti-PRP. [At Day 0]

   Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per millilitre (μg/mL).

9. Number of Subjects With Serious Adverse Events (SAEs). [During the entire study period (up to Day 46)]

   Assessed SAEs include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

10. Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/mL [At Day 0]

    Cut-off values assessed were greater than or equal to 6.2 milliinternational units per millilitre ( mIU/mL) in the sera of subjects seronegative before vaccination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 6 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects who had received 3 doses of Infanrix hexa™ or Infanrix-IPV/Hib™ in study NCT00307034.

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

• A male or female subject aged 5 years at the time of study entry.

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

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

Exclusion Criteria:

• Child in care.

• 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.

• Use of any investigational or non-registered product within 30 days prior to blood sampling.

• Evidence of previous or intercurrent diphtheria, tetanus, pertussis, polio, hepatitis B, and Hib vaccination or disease since the study NCT00307034, with the exception of hepatitis B vaccination in the DTPa-IPV/Hib group.

• Administration of immunoglobulins and/or any blood products within the 3 months prior to blood sampling.

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

• Family history of congenital or hereditary immunodeficiency.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Morvik		Norway	5124
2	GSK Investigational Site	Oslo		Norway	0130
3	GSK Investigational Site	Umeå		Sweden	SE-901 85
4	GSK Investigational Site	Örebro		Sweden	SE-702 11

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

• Silfverdal SA, Assudani D, Kuriyakose S, Van Der Meeren O. Immunological persistence in 5 y olds previously vaccinated with hexavalent DTPa-HBV-IPV/Hib at 3, 5, and 11 months of age. Hum Vaccin Immunother. 2014;10(10):2795-8. doi: 10.4161/21645515.2014.970494.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01358825
• Other Study ID Numbers: 115375; 2011-000943-26
• First Posted: May 24, 2011
• Last Update Posted: Jan 19, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Infanrix-IPV/Hib; Long-term follow up; Persistence; Infanrix hexa
• Additional relevant MeSH terms: Influenza, Human; Hepatitis B; Tetanus; Diphtheria; Poliomyelitis; Tetany

Study Results

Participant Flow

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 Hexa Group	Infanrix-IPV/Hib Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (administered intramuscularly) in study NCT00307034.
Period Title: Overall Study
STARTED	12	46
COMPLETED	12	45
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Infanrix Hexa Group	Infanrix-IPV/Hib Group	Total
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (administered intramuscularly) in study NCT00307034.	Total of all reporting groups
Overall Participants	12	46	58
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	5.0 (0.0)	5.0 (0.0)	5.0 (0.0)
Sex: Female, Male (Count of Participants)
Female	9 75%	14 30.4%	23 39.7%
Male	3 25%	32 69.6%	35 60.3%

Outcome Measures

1. Primary Outcome

Title	Number of Seroprotected Subjects Against Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T).
Description	A seroprotected subject is a subject with anti-D/anti-T antibody concentrations greater than (≥) or equal to 0.1 international units per milliliter (IU/mL)
Time Frame	At Day 0

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) Cohort, which included all subjects with blood sample available and who met all the eligibility criteria, complying with the procedure defined in the protocol and with no elimination code assigned.

Arm/Group Title	Infanrix Hexa Group	Infanrix-IPV/Hib Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (administered intramuscularly) in study NCT00307034.
Measure Participants	12	45
Anti-D	7 58.3%	28 60.9%
Anti-T	10 83.3%	34 73.9%

2. Primary Outcome

Title	Concentrations of Antibodies Against Anti-D and Anti-T
Description	Concentrations are presented as geometric mean concentrations (GMCs), expressed in milliinternational units per millilitre (mIU/mL).
Time Frame	At Day 0

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) Cohort, which included all subjects with blood sample available and who met all the eligibility criteria, complying with the procedure defined in the protocol and with no elimination code assigned.

Arm/Group Title	Infanrix Hexa Group	Infanrix-IPV/Hib Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (administered intramuscularly) in study NCT00307034.
Measure Participants	12	45
Anti-D	0.13	0.196
Anti-T	0.29	0.352

3. Primary Outcome

Title	Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Antifilamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations ≥5 ELISA Units Per Milliliter (EL.U/mL).
Description	Cut-off values assessed were greater than or equal to 5 ELISA units per millilitre (EL.U/mL) in the sera of subjects seronegative before vaccination.
Time Frame	At Day 0

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) Cohort, which included all subjects with blood sample available and who met all the eligibility criteria, complying with the procedure defined in the protocol and with no elimination code assigned.

Arm/Group Title	Infanrix Hexa Group	Infanrix-IPV/Hib Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (administered intramuscularly) in study NCT00307034.
Measure Participants	12	45
Anti-PT	0 0%	9 19.6%
Anti-FHA	12 100%	41 89.1%
Anti-PRN	8 66.7%	34 73.9%

4. Primary Outcome

Title	Concentrations of Antibodies Against Anti-PT, Anti-FHA and Anti-PRN.
Description	Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EL.U/mL).
Time Frame	At Day 0

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) Cohort, which included all subjects with blood sample available and who met all the eligibility criteria, complying with the procedure defined in the protocol and with no elimination code assigned.

Arm/Group Title	Infanrix Hexa Group	Infanrix-IPV/Hib Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (administered intramuscularly) in study NCT00307034.
Measure Participants	12	45
Anti-PT	2.5	4.2
Anti-FHA	32.6	50.7
Anti-PRN	6.2	11.9

5. Primary Outcome

Title	Number of Seroprotected Subjects Against Anti-hepatitis B Surface Antigen (Anti-HBs).
Description	Seroprotection = anti-HBs antibody concentration ≥ 10 milli-international units per milliliter (mIU/mL).
Time Frame	At Day 0

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) Cohort, which included all subjects with blood sample available and who met all the eligibility criteria, complying with the procedure defined in the protocol and with no elimination code assigned.

Arm/Group Title	Infanrix Hexa Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.
Measure Participants	12
Count of Participants [Participants]	5 41.7%

6. Primary Outcome

Title	Concentrations of Antibodies Against Anti-HBs.
Description	Concentrations are presented as geometric mean concentrations (GMCs), expressed in milliinternational units per millilitre (mIU/mL).
Time Frame	At Day 0

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) Cohort, which included all subjects with blood sample available and who met all the eligibility criteria, complying with the procedure defined in the protocol and with no elimination code assigned.

Arm/Group Title	Infanrix Hexa Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.
Measure Participants	12
Geometric Mean (95% Confidence Interval) [mIU/mL]	9

7. Primary Outcome

Title	Number of Seroprotected Subjects Against Anti-polyribosyl Ribitol Phosphate (Anti-PRP).
Description	A seroprotected subject is a subject with anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (μg/mL)
Time Frame	At Day 0

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) Cohort, which included all subjects with blood sample available and who met all the eligibility criteria, complying with the procedure defined in the protocol and with no elimination code assigned.

Arm/Group Title	Infanrix Hexa Group	Infanrix-IPV/Hib Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (administered intramuscularly) in study NCT00307034.
Measure Participants	12	45
Count of Participants [Participants]	10 83.3%	40 87%

8. Primary Outcome

Title	Concentrations of Antibodies Against Anti-PRP.
Description	Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per millilitre (μg/mL).
Time Frame	At Day 0

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) Cohort, which included all subjects with blood sample available and who met all the eligibility criteria, complying with the procedure defined in the protocol and with no elimination code assigned.

Arm/Group Title	Infanrix Hexa Group	Infanrix-IPV/Hib Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (administered intramuscularly) in study NCT00307034.
Measure Participants	12	45
Geometric Mean (95% Confidence Interval) [μg/mL]	0.404	0.886

9. Primary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs).
Description	Assessed SAEs 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 (up to Day 46)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Cohort, which included all subjects enrolled in the study.

Arm/Group Title	Infanrix Hexa Group	Infanrix-IPV/Hib Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (administered intramuscularly) in study NCT00307034.
Measure Participants	12	46
Count of Participants [Participants]	0 0%	0 0%

10. Primary Outcome

Title	Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/mL
Description	Cut-off values assessed were greater than or equal to 6.2 milliinternational units per millilitre ( mIU/mL) in the sera of subjects seronegative before vaccination.
Time Frame	At Day 0

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) Cohort, which included all subjects with blood sample available and who met all the eligibility criteria, complying with the procedure defined in the protocol and with no elimination code assigned.

Arm/Group Title	Infanrix Hexa Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.
Measure Participants	12
Count of Participants [Participants]	6 50%

Adverse Events

Time Frame	SAEs: during the entire study period (Day 0 to Day 46)
Adverse Event Reporting Description	As no vaccine was administered during the study, no safety data other than spontaneous SAEs were collected during the study.
Arm/Group Title	Infanrix Hexa Group		Infanrix-IPV/Hib Group
Arm/Group Description	Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix hexa™ (administered intramuscularly) in study NCT00307034.		Subjects aged 5 years previously vaccinated at 3, 5 and 11 months of age with 3 doses of Infanrix-IPV/Hib™ (administered intramuscularly) in study NCT00307034.
All Cause Mortality
	Infanrix Hexa Group		Infanrix-IPV/Hib Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Infanrix Hexa Group		Infanrix-IPV/Hib Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/46 (0%)
Other (Not Including Serious) Adverse Events
	Infanrix Hexa Group		Infanrix-IPV/Hib Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

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.