Long-term Persistence Study to Assess a Booster Dose of GSK Biologicals' Hib-MenC

Study Overview
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Brief Summary
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This protocol posting deals with objectives & outcome measures of the extension phase at Months 18, 30, 42, 54 and 66 post booster. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00352963). The objectives & outcome measures of the Booster phase/study are presented in a separate protocol posting (NCT number =NCT00323050). The purpose of this study is to evaluate the persistence of meningococcal serogroup C and Hib antibodies on a yearly basis for a period of 5.5 years after booster vaccination. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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This multicenter study is open. No vaccine will be administered during this persistence phase of the study. The subjects were randomized in the primary vaccination study 217744/097 (DTPa-HBV-IPV-097) and will not be further randomized in this study. The study has 3 groups with Meningitec™ primed group as control. The protocol was amended to allow for enrollment of subjects of the Meningitec™ primed control group who were boosted with Meningitec™ after the end of the booster study as per new local reccommendation in Spain.

Official Title
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Phase III, Open, Multicenter Study to Assess the Long-Term Persistence of a Booster Dose of GSK Biologicals' Hib-MenC Compared to a Booster Dose of Infanrix™ Hexa When Given to 14 Month-old Subjects Primed in Study DTPa-HBV-IPV-097 & Boosted in Study Hib-MenC-TT-010 BST: DTPa-HBV-IPV-097

Conditions
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Haemophilus Influenzae Type b, Neisseria Meningitidis

Intervention / Treatment
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* Biological: Haemophilus influenzae type b- and meningococcal (vaccine)
* Biological: Infanrix™ penta
* Biological: Infanrix™ hexa
* Biological: Engerix-B
* Biological: NeisVac-C™
* Biological: Infanrix™ IPV/HIB
* Biological: Meningitec™


Participation Criteria
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Eligibility Criteria
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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 in their third year of life at the time of the study initiation for the subjects who enter the study at Visit 1. The subjects who enter the study at Visit 2 should be in their fourth year of life at the time of the study initiation. 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. Having completed the booster vaccination study Hib-MenC-TT-010 BST:DTPA-HBV-IPV-097 (NCT=00323050). Subjects who are part of the Meningitec™ control group and who were not enrolled at Visit 1 can be enrolled at Visit 2 if they have completed the booster vaccination study Hib-MenC-TT-010 BST:DTPA-HBV-IPV-097 (NCT=00323050) and if they have received a fourth dose of Meningitec™ in their second year of life, after the booster study Hib-MenC-TT-010 BST:DTPA-HBV-IPV-097 (NCT=00323050) Exclusion Criteria: Previous administration of a booster dose of Hib or meningococcal serogroup C except booster study vaccines during the study Hib-MenC-TT-010 BST:DTPA-HBV-IPV-097. Subjects who received a 4th dose of Meningitec™ should be included in the study. History of H. influenzae type b, meningococcal serogroup C diseases.

Ages Eligible for Study
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Minimum Age: 31 Months
Maximum Age: 33 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Menitorix/Pediarix Group<br>Subjects were primed with 3 doses of Pediarix™ co-administered intramuscularly with Menitorix™ in the right and left thigh respectively in the primary study (NCT00352963) at 2, 4 and 6 months of age. This was followed by a booster dose of Menitorix™ administered intramuscularly in the left thigh between 13 and 14 months of age in study NCT00323050. No vaccines were administered during this long-term persistence phase of the study. | Biological: Haemophilus influenzae type b- and meningococcal (vaccine)<br>* Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age (group HibMenC) and as booster dose at 14 months of age (groups HibMenC and group NeisPoo).<br>Biological: Infanrix™ penta<br>* Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age<br>|
| Active Comparator: Infanrix hexa (or IPV/Hib)/NeisVac-C/Engerix-B/Menitorix Group<br>Subjects were either primed in the primary study (NCT00352963) with 3 doses of Infanrix™ hexa administered intramuscularly in the right thigh at 2, 4 and 6 months of age and 2 doses of NeisVac-C™ administered intramuscularly in the left thigh at 2 and 4 months of age or with Engerix-B at birth intramuscularly in the right thigh, Infanrix™ hexa intramusculary in the right thigh at 2 and 6 months of age and NeisVac-C™ intramuscularly in the left thigh at 2 and 4 months of age, Infanrix™ IPV/Hib was administered intramuscularly in the right thigh at 4 months of age. All subjects were boosted with Menitorix™ administered intramuscularly in the left thigh between 13 and 14 months of age in study NCT00323050. No vaccines were administered during this long-term persistence phase of the study. | Biological: Haemophilus influenzae type b- and meningococcal (vaccine)<br>* Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age (group HibMenC) and as booster dose at 14 months of age (groups HibMenC and group NeisPoo).<br>Biological: Infanrix™ hexa<br>* Intramuscular injection into the thigh as primary vaccination at 2, 4 and/or 6 months of age (groups NeisPoo and MenCCRM) and/or as booster dose at 14 months of age (group MenCCRM).<br>Biological: Engerix-B<br>* Intramuscular injection into the thigh as a birth dose<br>Biological: NeisVac-C™<br>* Intramuscular injection into the thigh as primary vaccination at 2 and 4 months of age.<br>Biological: Infanrix™ IPV/HIB<br>* Intramuscular injection into the thigh as primary vaccination at 4 months of age<br>|
| Active Comparator: Infanrix hexa/Meningitec Group<br>Subjects were primed with Infanrix™ hexa co-administered intramuscularly with Meningitec™ in the right and left thigh respectively at 2, 4 and 6 months of age during the primary study (NCT00352963), followed by a booster dose of Infanrix™ hexa intramuscularly in the right thigh between 13 and 14 months of age in study (NCT00323050). No vaccines were administered during this long-term persistence phase of the study. | Biological: Infanrix™ hexa<br>* Intramuscular injection into the thigh as primary vaccination at 2, 4 and/or 6 months of age (groups NeisPoo and MenCCRM) and/or as booster dose at 14 months of age (group MenCCRM).<br>Biological: Meningitec™<br>* Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Equal to or Above Cut-off Value of 1:8 | The cut-off value for the rSBA-MenC titers was equal to or above 1:8. 0 has been put as an arbitrary value for Month 18 in the Infanrix Hexa/Meningitec Group, as it was not addressed for reasons explained in the participant flow section. | 18, 30, 42, 54 and 66 months after booster dose (day 0) | 
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Equal to or Above Cut-off Value of 1:32 | The cut-off value for the rSBA-MenC titers was equal to or above 1:32. 0 has been put as an arbitrary value for Month 18 in the Infanrix Hexa/Meningitec Group, as it was not addressed for reasons explained in the participant flow section. | 18, 30, 42, 54 and 66 months after booster dose (day 0) | 
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Equal to or Above Cut-off Value of 1:128 | The cut-off value for the rSBA-MenC titers was equal to or above 1:128. 0 has been put as an arbitrary value for Month 18 in the Infanrix Hexa/Meningitec Group, as it was not addressed for reasons explained in the participant flow section. | 18, 30, 42, 54 and 66 months after booster dose (day 0) | 
| rSBA-MenC Titers | Titers are expressed as Geometric Mean Titers (GMTs). 0 has been put as an arbitrary value for Month 18 in the Infanrix Hexa/Meningitec Group, as it was not addressed for reasons explained in the participant flow section. | 18, 30, 42, 54 and 66 months after booster dose (day 0) | 
| Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Concentrations Equal to or Above Cut-off Value of 0.15 µg/mL (Microgram Per Milliliter) | The cut-off value was an anti-PRP concentration equal to or above 0.15 µg/mL (microgram per milliliter). | 18, 30, 42, 54 and 66 months after the booster dose (day 0) | 
| Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Concentrations Equal to or Above Cut-off Value of 1.0 µg/mL (Microgram Per Milliliter) | The cut-off value was an anti-PRP concentration equal to or above 1.0 µg/mL (microgram per milliliter). | 18, 30, 42, 54 and 66 months after the booster dose (day 0) | 
| Anti-PRP Concentrations | Concentrations are expressed as Geometric Mean Concentrations (GMCs) in µg/mL (microgram per milliliter). | 18, 30, 42, 54 and 66 months after the booster dose (day 0) | 
| Number of Subjects With Anti-polysaccharide C (Anti-PSC) Concentrations Equal to or Above Cut-off Value of 0.3 µg/mL (Microgram Per Milliliter) | The cut-off value was an anti-PSC concentration equal to or above 0.3 µg/mL (microgram per milliliter). 0 has been put as an arbitrary value for Month 18 in the Infanrix Hexa/Meningitec Group, as it was not addressed for reasons explained in the participant flow section. | 18, 30, 42, 54 and 66 months after the booster dose (day 0) | 
| Number of Subjects With Anti-polysaccharide C (Anti-PSC) Concentrations Equal to or Above Cut-off Value of 2.0 µg/mL (Microgram Per Milliliter) | The cut-off value was an anti-PSC concentration equal to or above 2.0 µg/mL (microgram per milliliter). 0 has been put as an arbitrary value for Month 18 in the Infanrix Hexa/Meningitec Group, as it was not addressed for reasons explained in the participant flow section. | 18, 30, 42, 54 and 66 months after the booster dose (day 0) | 
| Anti-PSC Concentrations | Concentrations for anti-PSC antibody were expressed as GMCs. | 18, 30, 42, 54 and 66 months after the booster dose (day 0) | 
| Number of Subjects With Serious Adverse Events | Serious adverse events assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | From last study contact of the booster study (NCT00323050) to Month 66 after booster dose (day 0) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H.influenzae type b Disease