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

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™

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.

Study Overview

• Status: Completed
• Conditions: Streptococcus Pneumoniae Vaccines; Infections, Streptococcal
• Intervention / Treatment: Biological: Synflorix (3-Dose); Biological: Synflorix (2-Dose); Biological: Prevenar 13 (Single Dose); Biological: Synflorix (Single Dose); Biological: Prevenar 13 (2-Dose)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 457
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Mexico, Mexico, 04530
    • GSK Investigational Site
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62210
      • GSK Investigational Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Synflorix Group; 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); 3 doses administered intramuscularly
Experimental: Prevnar 1 Group; 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); 2 doses administered intramuscularly; Biological: Prevenar 13 (Single Dose); 1 dose administered intramuscularly
Experimental: Prevnar 2 Group; 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); 1 dose administered intramuscularly; Biological: Prevenar 13 (2-Dose); 2 doses administered intramuscularly

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• de Los Santos AM, Rodriguez-Weber MA, Sanchez-Marquez P, Traskine M, Carreno-Manjarrez R, Cervantes-Apolinar MY, Strezova A, Ruiz-Guinazu J, Ortega-Barria E, Borys D. Can two different pneumococcal conjugate vaccines be used to complete the infant vaccination series? A randomized trial exploring interchangeability of the 13-valent pneumococcal conjugate vaccine and the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine. Expert Rev Vaccines. 2020 Nov;19(11):995-1010. doi: 10.1080/14760584.2020.1843431.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2012
• Primary Completion (Actual): July 15, 2013
• Study Completion (Actual): May 7, 2014

Study Registration Dates

• First Submitted: July 12, 2012
• First Submitted That Met QC Criteria: July 12, 2012
• First Posted (Estimate): July 16, 2012

Study Record Updates

• Last Update Posted (Actual): March 2, 2021
• Last Update Submitted That Met QC Criteria: February 8, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Synflorix; pneumococcal conjugate vaccine; Prevnar 13; Pneumococcal diseases
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia, Pneumococcal; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 115992; 2013-003479-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study is available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)