Primary Vaccination Study With a Pneumococcal Conjugate Vaccine in Healthy Children 6 to 8 Weeks of Age

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the immunogenicity in terms of antibody response and the safety/reactogenicity in terms of solicited and unsolicited symptoms and serious adverse events following primary vaccination of Taiwanese infants with pneumococcal conjugate vaccine GSK 1024850A co-administered with a diphtheria, tetanus, acellular pertussis (DTPa)-combined vaccine and rotavirus vaccine in children during the first 6 months of life.

Detailed Description
-----------------
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
-----------------
Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A, Infanrix Hexa and Rotarix

Conditions
-----------------
Infections, Rotavirus

Intervention / Treatment
-----------------
* Biological: Synflorix
* Biological: Infanrix hexa
* Biological: Rotarix


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects between, and including 6-8 weeks of age at the time of the first vaccination. Subjects for whom the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol. Written informed consent obtained from the parent(s) or guardian(s) of the subject. Free of obvious health problems as established by medical history and clinical examination before entering into the study. Born after a gestation period of 36 to 42 weeks inclusive. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, or planned use during the study period. Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting one month before each dose of vaccines and ending 7 days after dose 1 and dose 2 and one month after dose 3. 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. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth. A family history of congenital or hereditary immunodeficiency. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, rotavirus and/or Streptococcus pneumoniae; with the exception of vaccines where the first dose may be given within the first two weeks of life according to the national recommendations (e.g. Hepatitis B and Bacillus Calmette-Guérin (BCG)). History of, or intercurrent, diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b disease. Gastroenteritis within 7 days preceding the study vaccine administration (warrants deferral of the vaccination). Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal (GI) tract, intussusception (IS) or other medical condition determined to be serious by the investigator. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. History of any neurological disorders or seizures. Major congenital defects or serious chronic illness. Acute disease at the time of enrolment.

Ages Eligible for Study
-----------------
Minimum Age: 6 Weeks
Maximum Age: 8 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix group<br>Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age. | Biological: Synflorix<br>* Intramuscular injection, 3 doses.<br>* Other names: Pneumococcal conjugate vaccine GSK1024850A;Biological: Infanrix hexa<br>* Intramuscular injection, 3 doses.<br>* Other names: DTPa-HBV-IPV/Hib;Biological: Rotarix<br>* Oral, 2 doses.<br>* Other names: HRV vaccine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Anti-Protein D Antibodies | Concentrations are given as geometric mean concentrations (GMC) and expressed in Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter (EL.U/mL). | One month after the third dose | 
| Concentration of Anti-Pneumococcal Antibodies | Concentrations are given as geometric mean titers (GMC) and expressed in microgram per milliliter (µg/mL). The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. | One month after the third dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-Protein D Antibody Concentrations Above the Cut-Off Value | Anti-protein D antibody cut-off value assessed was greater than or equal to 100 Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter (EL.U/mL). | Before the first dose (pre) and one month after (post) the third dose | 
| Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value | Anti-pneumococcal antibody cut-off value assessed was 0.05 microgram per milliliter (μg/mL). The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. | Before the first dose (pre) and one month after (post) the third dose | 
| Number of Subjects With Cross-Reactive Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value | Anti-pneumococcal antibody cut-off value assessed was 0.05 microgram per milliliter (µg/mL). | One month after the third dose | 
| Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value | Cut-off value for opsonophagocytic activity against pneumococcal antibody assessed was greater than or equal to 1:8 titer. | One month after the third dose | 
| Number of Subjects With Opsonophagocytic Activity Against Cross-Reactive Pneumococcal Serotypes Above the Cut-Off Value | Cut-off value for opsonophagocytic activity against pneumococcal antibody assessed was greater than or equal to 1:8 titer. | One month after the third dose | 
| Number of Subjects With Anti-Polyribosyl-Ribitol Phosphate Antibody Concentrations Above the Cut-Off Value | Anti-polyribosyl-ribitol phosphate antibody cut-off value assessed was greater than or equal to 0.15 microgram per milliliter (μg/mL). | One month after the third dose | 
| Number of Subjects With Anti-Diphteria and Anti-Tetanus Toxoids Antibody Concentrations Above the Cut-Off Value | Anti-diphteria and anti-tetanus toxoids antibody cut-off values assessed were greater than or equal to 0.10 International Units per milliliter (IU/mL). | One month after the third dose | 
| Number of Subjects With Anti-Pertussis (PT), Anti-Filamentous Hemagglutinin (FHA) and Anti-Pertactin (PRN) Antibody Concentrations Above the Cut-Off Value | Anti-PT, anti-FHA and anti-PRN cut-off values assessed were greater than or equal to 5 Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter (EL.U/mL). | One month after the third dose | 
| Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Above the Cut-Off Value | Anti-HBs antibody cut-off value assessed was greater than or equal to 10 milli-International Units per milliliter (mIU/mL). | One month after the third dose | 
| Number of Subjects With Anti-Poliovirus 1, 2 and 3 Antibody Titers Above the Cut-Off Value | Anti-poliovirus 1, 2 and 3 antibody cut-off value assessed was greater than or equal to 1:8 titer. | One month after the third dose | 
| Number of Subjects With Anti-rotavirus Immunoglobulin A Antibody Concentrations Above the Cut-Off Value | Anti-rotavirus IgA antibody cut-off value assessed was greater than or equal to 20 Units per milliliter (U/mL). | Four months after the administration of the second dose of Rotarix™ vaccine | 
| Number of Subjects Reporting Solicited Symptoms | Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include diarrhoea, drowsiness, fever, irritability, loss of appetite, and vomiting | During the 4-day (Day 0-3) period after each dose | 
| Number of Subjects Reporting Unsolicited Adverse Events (AE) | An AE is 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 | During the 31-day (Day 0-30) period after each dose | 
| Number of Subjects Reporting Serious Adverse Events (SAE) | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | Up to one month after the third dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pneumococcal vaccine., Pneumococcal disease, Safety, Immunogenicity, Primary vaccination