Immunogenicity and Safety Study of Infanrix Hexa in Healthy Infants Born to Mothers Vaccinated With Boostrix™ During Pregnancy or Immediately Post-delivery

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity and safety of GSK Biologicals' Infanrix hexa, given in the primary vaccination schedule to infants born to pregnant women who participated in study 116945 [DTPA (BOOSTRIX)-047]. This study will help us evaluate if the presence of transplacentally transferred maternal antibodies interfere with the immune response to primary vaccination with Infanrix hexa and a co-administered pneumococcal conjugate vaccine given as a part of this study in infants.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Combined Diphtheria-tetanus-acellular Pertussis-hepatitis B-inactivated Polio-virus and Haemophilus Influenzae Type b Vaccine (Infanrix Hexa™) (217744) in Healthy Infants Born to Mothers Vaccinated With Boostrix™ During Pregnancy or Immediately Post-delivery

Conditions
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Acellular Pertussis, Tetanus, Poliomyelitis, Diphtheria, Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b Vaccines

Intervention / Treatment
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* Biological: Infanrix hexa
* Drug: Prevnar13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits). Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure. A male or female between, 6 and 14 weeks of age (including 6 weeks and up to and including 14 weeks and 6 days of age) at the time of the first vaccination. Healthy subjects as established by medical history and clinical examination before entering into the study. Born to a mother enrolled in study 116945 [DTPA (BOOSTRIX)-047]. Medically stable* prematurely born infants, born after a gestation period of 27-36 weeks may be enrolled in the study at the discretion of the investigator. Medically stable refers to the condition of premature infants who do not require significant medical support or ongoing management for debilitating disease and who have demonstrated a clinical course of sustained recovery by the time they receive the first dose of study vaccine. Exclusion Criteria: Child in care Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting at birth prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥0.5mg/kg/day, or equivalent. Inhaled and topical steroids are allowed. Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). Administration of any chronic drug therapy to be continued during the study period. A vaccine not foreseen by the study protocol administered during the period starting from 30 days before each dose of vaccine and ending 30 days after*, with the exception of inactivated influenza vaccine and other vaccines given as a part of the national/regional immunisation schedule, that are allowed at any time during the study period. In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) is organised by the public health authorities, outside the routine immunisation program, the time period described above can be reduced if necessary for that vaccine provided it is licensed and used according to its SPC or package insert (PI) and according to the local governmental recommendations and provided a written approval of the Sponsor is obtained. 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 vaccine/product (pharmaceutical product or device). Previous vaccination against Hib, diphtheria, tetanus, pertussis, pneumococcus, and/or poliovirus since birth. History of Hib, diphtheria, tetanus, pertussis, pneumococcal, poliovirus and hepatitis B diseases. Any confirmed or suspected immunosuppressive or immunodeficient condition including severe combined immunodeficiency disease (SCID), based on medical history and physical examination (no laboratory testing required). Family history of congenital or hereditary immunodeficiency. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Major congenital defects Serious chronic illness. History of any neurological disorders or seizures. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥37.5°C/99.5°F for oral, axillary or tympanic route, or ≥38.0°C/100.4°F for rectal route. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products during the period starting at birth before the first dose of study vaccines or planned administration during the study period. Hypersensitivity to latex.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 14 Weeks

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: dTpa Group<br>This group will consist of infants born to mothers belonging to the dTpa Group in study 116945 [DTPA (BOOSTRIX)-047] i.e. who received a single dose of BoostrixTM during pregnancy and a dose of placebo immediately post-delivery. All infants in this group will receive Infanrix hexaTM co-administered with Prevenar 13®. | Biological: Infanrix hexa<br>* • All subjects will receive Infanrix hexa at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. Infanrix hexa is administered intramuscularly to the right thigh.<br>Drug: Prevnar13<br>* • All subjects will receive Infanrix hexa co-administered with Prevenar13* at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. *In some countries/regions with an Infanrix hexa 3-dose vaccination schedule, Prevenar 13 could be administered as 2-doses or 3-doses primary vaccination schedule (according to the routine national immunisation schedule). Prevnar13 is administered intramuscularly to the left thigh.<br>|
| Active Comparator: Control Group<br>This group will consist of infants born to mothers belonging to the Control group in study 116945 [DTPA (BOOSTRIX)-047], i.e. who received a single dose of placebo during pregnancy and a dose of BoostrixTM immediately post-delivery. All infants in this group will receive Infanrix hexaTM co-administered with Prevenar 13®. | Biological: Infanrix hexa<br>* • All subjects will receive Infanrix hexa at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. Infanrix hexa is administered intramuscularly to the right thigh.<br>Drug: Prevnar13<br>* • All subjects will receive Infanrix hexa co-administered with Prevenar13* at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. *In some countries/regions with an Infanrix hexa 3-dose vaccination schedule, Prevenar 13 could be administered as 2-doses or 3-doses primary vaccination schedule (according to the routine national immunisation schedule). Prevnar13 is administered intramuscularly to the left thigh.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens | Vaccine response to the PT, FHA and PRN antigens, is defined as the appearance of antibodies in subjects who were initially seronegative (i.e., with concentrations lower than (<) the cut-off value of the assay), or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e., with concentrations greater than or equal to (≥) the cut-off value of the assay). Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, 2.187 IU/mL for anti-PRN. | 1 month after the last dose of the primary vaccination | 
| Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off | A seroprotected subject is a subject whose antibody concentration/titre was ≥ the level defining clinical protection, of 0.1 International Units per milliliter (IU/mL). | 1 month after the last dose of the primary vaccination | 
| Number of Seroprotected Subjects With Anti Hepatitis B (Anti-HBs) Antibody Concentration Above or Equal to the Assay Cut-off | A seroprotected subject is a subject whose antibody concentration/titre was ≥ to the level defining clinical protection, of 10 micro International Units per milliliter (mIU/mL). | 1 month after the last dose of the primary vaccination | 
| Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8 | A seroprotected subject is a subject whose antibody titre was ≥ the level defining clinical protection, of 8 ED50. | 1 month after the last dose of the primary vaccination | 
| Number of Seroprotected Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Above or Equal to the Assay Cut-off | A seroprotected subject is a subject whose antibody concentration/titre was ≥ the level defining clinical protection, of 0.15 micrograms per milliliter (µg/mL). | 1 month after the last dose of the primary vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off. | A seroprotected subject is a subject whose antibody concentration was ≥ the level defining clinical protection, of 0.1 IU/mL. | Before the first dose of Infanrix hexa | 
| Anti-D and Anti-T Antibody Concentrations | Antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in IU/mL. | Before the first dose of Infanrix hexa | 
| Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | A seropositive subject is a subject whose antibody concentration is ≥ the assay cut-off defined. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA,2.187 IU/mL for anti-PRN | Before the first dose of Infanrix hexa | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PT, anti-FHA and anti-PRN antibody concentrations were expressed as GMCs and measured in IU/mL. | Before the first dose of Infanrix hexa | 
| Anti-D and Anti-T Antibody Concentrations | Antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in IU/mL. | 1 month after the last dose of the primary vaccination | 
| Anti-Polio Type 1, 2 and 3 Antibody Titers | Anti-Polio type 1, 2 and 3 antibody titers were expressed as geometric mean titers (GMT). | 1 month after the last dose of the primary vaccination | 
| Anti-HBs Antibody Concentrations | Anti-HBs antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in mIU/mL. | 1 month after the last dose of the primary vaccination | 
| Anti-PRP Antibody Concentrations | Anti-PRP antibody concentrations were expressed as GMCs and measured in µg/mL. | 1 month after the last dose of the primary vaccination | 
| Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations | Anti-PT, anti-FHA, anti-PRN antibody concentrations were expressed as GMCs and measured in IU/mL. | 1 month after the last dose of the primary vaccination | 
| Anti-pneumococcal Antibody Concentrations | Assessed anti-pneumococcal serotypes were (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F), expressed as GMCs and measured in µg/mL. | 1 month after the last dose of the primary vaccination | 
| Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | A seropositive subject is a subject whose antibody concentration is ≥ the assay cut-off defined. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA,2.187 IU/mL for anti-PRN | 1 month after the last dose of the primary vaccination | 
| Number of Subjects With Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Solicited local symptoms were assessed by each and across dose. | During the 4-day (Day 0-Day 3) follow-up period after each vaccination | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite and fever [defined as axillary route temperature ≥ 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Solicited general symptoms were assessed by each and across dose. | During the 4-day (Day 0-Day 3) follow-up period after each vaccination | 
| Number of Subjects With Unsolicited Adverse Events | 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 is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | During the 31-day (days 0-30) follow-up period after each vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. | From Day 0, prior to vaccination until the study end, at Month 3 or 5 (depending on vaccination schedule of the country) |