Primary Vaccination With Either Synflorix™ or Prevenar 13™ or Both Vaccines and Booster Vaccination With Synflorix™

Study Overview
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Brief Summary
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The primary aim of this study is to assess the reactogenicity of Synflorix vaccine and Prevenar 13 vaccine after primary vaccination at 2 and 4 months of age with either Synflorix or Prevenar 13 vaccine or Prevenar 13 and Synflorix, respectively. In addition, this study aims at assessing the safety, reactogenicity, immunogenicity and antibody persistence (approximately 8-11 months following primary vaccination) of the Synflorix vaccine and Prevenar 13 vaccine after primary vaccination at 2 and 4 months of age with either Synflorix or Prevenar 13 vaccine or Prevenar 13 and Synflorix, respectively. This study also aims at assessing the safety, reactogenicity and immunogenicity of the Synflorix vaccine when given as a booster dose at 12-15 months of age following primary vaccination at 2 and 4 months of age with either Synflorix vaccine or Prevenar 13 vaccine or Prevenar 13 and Synflorix respectively.

Detailed Description
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This study is partially blinded as the primary phase will be conducted in an observer-blind method and booster phase will be open method.

Official Title
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Two-dose Primary Vaccination With Either GSK Biologicals' 10-valent Pneumococcal Vaccine (Synflorix™) or Pfizer's Prevenar 13™ or Both Vaccines Followed by a Booster Dose of Synflorix™

Conditions
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Infections, Streptococcal, Streptococcus Pneumoniae Vaccines

Intervention / Treatment
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* Biological: Synflorix (3-Dose)
* Biological: Synflorix (2-Dose)
* Biological: Synflorix (Single Dose)
* Biological: Prevenar 13 (Single Dose)
* Biological: Prevenar 13 (2-Dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 between, and including, 6-12 weeks 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 after a gestation period of at least 36 weeks. Written informed consent obtained from the parent(s)/LAR(s) of the subject. Exclusion Criteria: Child in care. Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccines, or planned use during the entire study period. Chronic administration of immunosuppressants or other immune-modifying drugs since birth or planned use during the study. 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. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine. Major congenital defects or serious chronic illness. History of any seizures or progressive neurological disease. Administration of immunoglobulins and/or blood products since birth or planned use during the study. Acute disease and/or fever at the time of enrolment. Previous vaccination or planned vaccination during the study with any pneumococcal vaccine.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Synflorix Group<br>Subjects who were primed with two doses of Synflorix vaccine, administered intramuscularly into the right or left thigh, at 2 and 4 months of age, received a booster dose of Synflorix vaccine, administered intramuscularly into the right or left anterolateral thigh or in the deltoid, at 12-15 months of age. | Biological: Synflorix (3-Dose)<br>* 3 doses administered intramuscularly<br>|
| Experimental: Prevnar 1 Group<br>Subjects who were primed with Prevnar 13 and Synflorix vaccines, administered intramuscularly into the right or left thigh, at 2 and 4 months of age respectively, received a booster dose of Synflorix vaccine, administered intramuscularly into the right or left thigh or in the deltoid, at 12-15 months of age. | Biological: Synflorix (2-Dose)<br>* 2 doses administered intramuscularly<br>Biological: Prevenar 13 (Single Dose)<br>* 1 dose administered intramuscularly<br>|
| Experimental: Prevnar 2 Group<br>Subjects who were primed with two doses of Prevnar 13 vaccine, administered intramuscularly into the right or left thigh, at 2 and 4 months of age, received a booster dose of Synflorix vaccine, administered intramuscularly into the right or left anterolateral thigh or in the deltoid, at 12-15 months of age. | Biological: Synflorix (Single Dose)<br>* 1 dose administered intramuscularly<br>Biological: Prevenar 13 (2-Dose)<br>* 2 doses administered intramuscularly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Grade 3 Adverse Events (AEs) (Solicited and Unsolicited) - Primary Period | The number of subjects with Grade 3 AEs (solicited and unsolicited), during the 31-day post-vaccination period following each primary dose is reported. | Within 31-day (Day 0-Day 30) after any dose of primary vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms - Primary Period | Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/spontaneously painful. Grade 3 swelling/redness was defined as swelling/redness larger than (>) 30 millimeters (mm). Any is defined as incidence of the specified symptom regardless of intensity. | During the 4-day (Days 0-3) post-vaccination period following each primary dose | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms - Booster Period | Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/spontaneously painful. Grade 3 swelling/redness was defined as swelling/redness larger than (>) 30 millimeters (mm). Any is defined as incidence of the specified symptom regardless of intensity. | During the 4-day (Days 0-3) post-booster vaccination period | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms - Primary Period | Solicited general symptoms assessed include drowsiness, fever (defined as axillary temperature ≥ 37.5°C), irritability, and loss of appetite. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (axillary temperature) above (>) 39.5 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all. Any is defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. | During the 4-day (Days 0-3) post-vaccination period following each primary dose | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms - Booster Period | Solicited general symptoms assessed include drowsiness, fever (defined as axillary temperature ≥ 37.5°C), irritability, and loss of appetite. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (axillary temperature) above (>) 39.5 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all. Any is defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. | During the 4-day (Days 0-3) post-booster vaccination period | 
| Number of Subjects Reporting Any and Grade 3 Symptoms (Solicited and Unsolicited) - Booster Period | The number of subjects with any and grade 3 symptoms (solicited and unsolicited), during the 31-day post-booster vaccination period is reported. | During the 31-day (Days 0-30) post-booster vaccination period | 
| Number of Subjects With Unsolicited AEs - Primary Period | An unsolicited 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. Any is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. | During the 31-day (Days 0-30) post-primary vaccination period | 
| Number of Subjects With Unsolicited AEs - Booster Period | An unsolicited 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. Any is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. | During the 31-day (Days 0-30) post-booster vaccination period | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | From first vaccination (Month 0) up to study end (11-14 months) | 
| Antibody Concentrations Against Pneumococcal Serotypes | Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 µg/mL. | At study Month 3 (one month after the primary vaccination), at study Month 10 (prior to booster vaccination) and at study Month 11 (one month after the booster vaccination) | 
| Concentrations of Antibodies Against Protein D (Anti-PD) | Anti-PD antibody concentrations were measured by Enzyme-linked Immunosorbent Assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The cut-off of the assay was an anti-PD antibody concentration higher than or equal to (≥) 153 EL.U/mL. | At study Month 3 (one month after primary vaccination) and at study Month 11 (one month after booster vaccination) | 
| Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes | The immunogenicity assessment was based on multiplex opsonophagocytic activity assay (MOPA). Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). The cut-off of the assay was a serotype specific titer for opsonophagocytic activity higher than or equal to (≥) the Lower Limit of Quantification (LLOQ) i.e.: 14 for OPA-1, 11 for OPA-3; 40 for OPA-4; 15 for OPA-5; 45 for OPA-6A; 29 for OPA-6B; 28 for OPA-7F; 39 for OPA-9V; 16 for OPA-14; 40 for OPA-18C; 13 for OPA-19A; 33 for OPA-19F and 40 for OPA-23F. | At study Month 3 (one month after the primary vaccination), at study Month 10 (prior to booster vaccination) and at study Month 11 (one month after the booster vaccination) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumococcal conjugate vaccine, Synflorix, Prevnar 13, Pneumococcal diseases