This Study Will Evaluate the Immunogenicity, Reactogenicity and Safety of the Routine Infant Vaccines Pediarix®, Hiberix® and Prevenar 13® When Co-administered With GlaxoSmithKline (GSK) Biologicals' Liquid Human Rotavirus Vaccine (HRV) as Compared to GSK's Licensed Lyophilized Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to assess if there is any immune interference between the Porcine circovirus free (PCV-free) liquid Human rotavirus (HRV) vaccine and routine infant vaccinations currently in use in the US, namely Pediarix®, Hiberix® and Prevenar 13® as compared to the currently licensed lyophilized formulation of the HRV vaccine when co-administered with the same routine vaccinations in healthy infants 6-12 weeks of age

Official Title
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Immunogenicity, Reactogenicity and Safety Study of Pediarix®, Hiberix® and Prevenar 13® Co-administered With Two Different Formulations of GSK Biologicals' HRV Vaccine (444563) in Healthy Infants 6-12 Weeks of Age

Conditions
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Rotavirus Infection, Rotavirus Vaccines

Intervention / Treatment
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* Biological: Rotarix
* Biological: Pediarix
* Biological: Hiberix
* Biological: Prevenar 13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects' parent(s)/[LAR(s)] who, in the opinion of the investigator can and will comply with the requirements of the protocol. A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination. Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure. Healthy subjects as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Child in care. Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day-29 to Day 1), or planned use during the study period. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone (≥0.5 mg/kg/day, or equivalent). Inhaled and topical steroids are allowed. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Administration of long-acting immune-modifying drugs at any time during the study period. Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before the first dose of vaccine administration and ending at Visit 4, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study, if administered at a site which is different from the sites used to administer the co-administered vaccines. 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. Uncorrected congenital malformation of the gastrointestinal tract that would predispose for Intussusception (IS). History of IS. Very prematurely born infants (born ≤28 weeks of gestation). Family history of congenital or hereditary immunodeficiency. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Major congenital defects or serious chronic illness. Previous vaccination against Haemophilus type b (Hib), diphtheria, tetanus, pertussis, pneumococcus, RV and/or poliovirus. Previous confirmed occurrence of RV GE, Hib, diphtheria, tetanus, pertussis, pneumococcus, hepatitis B and/or polio disease. Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. GE within 7 days preceding the study vaccine administration. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. Hypersensitivity to latex. History of any neurological disorders or seizures. History of Severe combined immunodeficiency (SCID). Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥38.0°C/100.4°F. The preferred location for measuring temperature in this study will be the oral cavity, the axilla and the rectum. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 12 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HRV PCV-free Liq Group<br>Healthy female or male subjects, between and including 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination who received two doses of oral live-attenuated human rotavirus (HRV) vaccine in PCV-free liquid formulation, according to a 0, 2-month schedule, co-administered with one dose of each Pediarix, Hiberix and Prevnar-13 at three timepoints (day 1, month 2 and month 4). PCV-free implies no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used. | Biological: Rotarix<br>* Two doses administered orally according to a 0, 2 month schedule as per the immunization schedule for HRV vaccine administration in the US.<br>* Other names: GSK Biologicals' lyophilized formulation of oral live attenuated HRV vaccine.;Biological: Pediarix<br>* Three doses administered intramuscularly according to a 0, 2, 4 month schedule.<br>* Other names: hepatitis B (recombinant) and inactivated poliovirus vaccine.;Biological: Hiberix<br>* Three doses administered intramuscularly according to a 0, 2, 4 month schedule.<br>* Other names: GSK Biologicals' Haemophilus b conjugate vaccine (tetanus toxoid conjugate);Biological: Prevenar 13<br>* Three doses administered intramuscularly according to a 0, 2, 4 month schedule.<br>* Other names: Pfizer's Pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 Protein);|
| Active Comparator: HRV Lyo Group<br>Healthy female or male subjects, between and including 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination who received two doses of oral live-attenuated human rotavirus (HRV) vaccine in lyophilized formulation, according to a 0, 2-month schedule, co-administered with one dose of each Pediarix, Hiberix and Prevnar-13 at three timepoints (day 1, month 2 and month 4). | Biological: Rotarix<br>* Two doses administered orally according to a 0, 2 month schedule as per the immunization schedule for HRV vaccine administration in the US.<br>* Other names: GSK Biologicals' lyophilized formulation of oral live attenuated HRV vaccine.;Biological: Pediarix<br>* Three doses administered intramuscularly according to a 0, 2, 4 month schedule.<br>* Other names: hepatitis B (recombinant) and inactivated poliovirus vaccine.;Biological: Hiberix<br>* Three doses administered intramuscularly according to a 0, 2, 4 month schedule.<br>* Other names: GSK Biologicals' Haemophilus b conjugate vaccine (tetanus toxoid conjugate);Biological: Prevenar 13<br>* Three doses administered intramuscularly according to a 0, 2, 4 month schedule.<br>* Other names: Pfizer's Pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 Protein);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Above or Equal to Cut-off Value. | Immunogenicity was assessed using Enzyme Linked Immunosorbent Assay (ELISA) in terms of seroprotection rates against diphtheria toxoid. A seroprotected subject is a subject whose antibody concentration is greater than or equal to (≥) the level defining clinical protection. The following seroprotection thresholds were applicable:anti-D antibody concentrations ≥ 0.1 International Units/milliliter (IU/mL), anti-T antibody concentrations ≥ 0.1 IU/mL. | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Number of Seroprotected Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above or Equal to Cut-off Value. | Immunogenicity was assessed using ChemiLuminescence ImmunoAssay (CLIA) in terms of seroprotection rates against Hepatitis B. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-HB antibody concentrations ≥ 10 milli International Units/milliliter (mIU/mL). | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value. | Immunogenicity was assessed using virus micro-neutralization test in terms of seroprotection rates against polio virus types 1, 2 and 3. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-polio virus types 1, 2 and 3 types antibody titers ≥ 8 Estimated Dose 50% (ED50). | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations. | Antibody concentrations against PT, FHA and PRN were determined and expressed as Geometric Mean Concentrations (GMCs).The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Antibody concentrations against pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) were determined and expressed as GMCs in micrograms per milliliter (µg/mL).The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 0.15 µg/mL. | Immunogenicity was assessed in terms of seroprotection rates against PRP antibodies. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-PRP antibody concentrations ≥ 0.15 µg/mL. | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 1.0 µg/mL. | Immunogenicity was assessed in terms of seroprotection rates against PRP antibodies. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-PRP antibody concentrations ≥ 1.0 µg/mL. | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies. | Seroresponse is defined as the percentage of subjects showing an antibody concentration above a threshold that leads to 95% seroresponse in the HRV lyophilized Group. The cut-offs used were as follows: anti-PT (18.566 IU/mL), anti-FHA (35.711 IU/mL) and anti-PRN (11.034 IU/mL). | At Month 5 (One month after Dose 3 of co-administered vaccines) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects With Anti-Rota Virus Immunoglobulin A (Anti-RV IgA) Antibody Concentrations Above or Equal to Cut-off Value of 20 Units/Milliliter (U/mL). | Immunogenicity was assessed in terms of seropositivity against Rota virus IgA antibodies. The cut off used was ≥ 20 U/mL. | At Month 5 (Three months after Dose 2 of HRV vaccine) | 
| Number of Seropositive Subjects With Anti-RV IgA Antibody Concentrations Above or Equal to Cut-off Value of 90 U/mL. | Immunogenicity was assessed in terms of seropositivity against Rota virus IgA antibodies. The cut off used was ≥ 90 U/mL. | At Month 5 (Three months after Dose 2 of HRV vaccine) | 
| Number of Seropositive Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above or Equal to Cut-off Value. | Immunogenicity was assessed using ELISA technique in terms of seropositivity against PT, FHA and PRN antibodies. The cut-offs for antibodies were the Lower Limit Of Quantification (LLOQ) of the assays which were ≥ 2.693 IU/mL (anti-PT), ≥ 2.046 IU/mL (anti-FHA) and ≥ 2.187 IU/mL (anti-PRN). The Limit of Quantification is the lowest analyte concentration that can be quantitatively detected with a stated accuracy and precision, and LLOQ is the lowest standard curve point obtained by extrapolation, that can still be used for quantification. | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Immunogenicity was assessed using ELISA technique in terms of seropositivity against Pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) antibodies. The cut-off used was ≥ 0.35 µg/mL. | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations. | Antibody concentrations against diphtheria and tetanus were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Immunogenicity in Terms of Anti-PRP Antibody Concentrations. | Antibody concentrations against PRP were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Immunogenicity in Terms of Anti-HBs Antibody Concentrations. | Antibody concentrations against Hepatitis B were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. | Antibody concentrations against Poliovirus types 1, 2 and 3 were determined and expressed as Geometric Mean Titers (GMTs). | At Month 5 (One month after Dose 3 of co-administered vaccines) | 
| Number of Subjects With Any Solicited General Adverse Events (AEs). | Assessed solicited general AEs were cough/runny nose; diarrhoea; fever measured by 3 routes which were oral, axillary and rectal, defined as temperature ≥ 38.0 degrees Celsius (°C); irritability; loss of appetite and vomiting. Any = any solicited general AE irrespective of its intensity grade and relationship to vaccination | During the 8-day (Days 1-8) follow-up period after each HRV vaccination. | 
| Number of Subjects With Any Unsolicited AEs. | Unsolicited AEs assessed include any AE reported in addition to those solicited during the clinical study. Also any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms were reported as an unsolicited AE. Any= Any unsolicited AE irrespective of its intensity grade and relationship to vaccination. | During the 31-day (Days 1-31) follow-up period after each HRV vaccination. | 
| Number of Subjects With Any Serious Adverse Events (SAEs). | SAEs assessed include any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity. | During the entire study period (Day 1 to Month 10) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, lyophilized formulation, United States, Reactogenicity, Safety, Porcine circovirus -free, Human rotavirus vaccine, liquid formulation, Healthy infants