Safety & Immunogenicity of Pneumococcal Vaccine 2189242A in Children Aged 12-23 Months at the Time of First Vaccination

Safety, Reactogenicity and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Investigational Vaccination Regimen in Children Aged 12-23 Months at the Time of First Vaccination.

This study will assess the safety, reactogenicity and immunogenicity of different formulations of GSK Biologicals' pneumococcal vaccine 2189242A when administered alone or in combination with the 10-valent pneumococcal conjugate vaccine (GSK1024850A vaccine) as a 2-dose primary vaccination course followed by a booster dose in healthy children aged 12-23 months at the time of first vaccination. Considering that febrile reactions are frequently observed following pneumococcal vaccination, usually co-administered with other routine paediatric vaccines, the primary study objective will focus on evaluating the increase in grade 3 fever (i.e. rectal temperature >40.0°C).

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: Pneumococcal vaccine GSK2189242A (formulation 1); Biological: Pneumococcal vaccine GSK2189242A (formulation 2); Biological: Pneumococcal vaccine GSK2189242A combined with pneumococcal vaccine GSK1024850A (formulation 3); Biological: Pneumococcal vaccine GSK2189242A combined with pneumococcal vaccine GSK1024850A (formulation 4); Biological: Pneumococcal vaccine GSK1024850A

• Study Type: Interventional
• Enrollment (Actual): 257
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Chomutov, Czechia, 43003
    • GSK Investigational Site
  • Decin, Czechia, 405 01
    • GSK Investigational Site
  • Nachod, Czechia, 547 01
    • GSK Investigational Site
  • Odolena voda, Czechia, 25070
    • GSK Investigational Site
  • Ostrava - Poruba, Czechia, 70868
    • GSK Investigational Site
  • Pardubice, Czechia, 532 03
    • GSK Investigational Site
  • Plzen, Czechia, 305 99
    • GSK Investigational Site
  • Praha 4, Czechia, 140 00
    • GSK Investigational Site
  • Praha 6, Czechia, 1600
    • GSK Investigational Site
  • Znojmo, Czechia, 669 00
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol
• Male or female between, and including, 12 and 23 months of age at the time of the first vaccination.
• Written informed consent obtained from the parents/LAR(s) of the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

• Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Planned administration/administration of a vaccine not foreseen by the study protocol during the study period starting from 30 days before each dose and ending 30 days after each dose of vaccine(s).
• Previous vaccination against S. pneumoniae since birth.
• History of any hypersensitivity reaction following any previous vaccination.
• Eczema and any history of allergy
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required), including human immunodeficiency virus infection.
• A family history of congenital or hereditary immunodeficiency.
• Major congenital defects or any chronic illness.
• History of any neurologic disorders or seizures.
• Acute disease and/or fever at the time of enrolment.
• Fever is defined as temperature >= 37.5°C on oral or axillary setting, or >= 38.0°C on rectal setting.
• Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
• Administration of immunoglobulins and/ or any blood products within the 3 months preceding the first dose of study vaccine or planned use during the study period.
• Child in care.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 2	Biological: Pneumococcal vaccine GSK2189242A (formulation 2); Three doses will be administered intramuscularly, at Month 0, 2 and 6
Experimental: Group 1	Biological: Pneumococcal vaccine GSK2189242A (formulation 1); Three doses will be administered intramuscularly, at Month 0, 2 and 6.
Experimental: Group 3	Biological: Pneumococcal vaccine GSK2189242A combined with pneumococcal vaccine GSK1024850A (formulation 3); Three doses will be administered intramuscularly, at Month 0, 2 and 6
Experimental: Group 4	Biological: Pneumococcal vaccine GSK2189242A combined with pneumococcal vaccine GSK1024850A (formulation 4); Three doses will be administered intramuscularly, at Month 0, 2 and 6
Experimental: Control Group	Biological: Pneumococcal vaccine GSK1024850A; Three doses will be administered intramuscularly, at Month 0, 2 and 6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Fever > 40.0°C (Rectal Temperature)	The number of subjects with rectal temperature higher (>) than 40.0 degrees Celsius (°C) is reported.	Within 7 days (Day 0-Day 6) following at least one dose of the primary vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms	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 7-day (Days 0-6) post-vaccination period following each dose (Dose 1, Dose 2 and Booster dose)
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms	Solicited general symptoms assessed include drowsiness, fever (defined as rectally temperature ≥ 38.0°C), irritability, and loss of appetite. Grade 3 drowsiness = drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectally temperature) above (>) 40.0 degree Celsius (°C). Grade 3 irritability = crying that could not be comforted/preventing normal activity. Grade 3 loss of appetite = not eating at all. "Any" is defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination.	During the 7-day (Days 0-6) post-vaccination period following each dose (Dose 1, Dose 2, Booster dose)
Number of Subjects With Unsolicited Adverse Events (AEs)	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. "Any" is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.	During the 31-day (Days 0-30) follow-up period after each primary dose
Number of Subjects With Unsolicited Adverse Events (AEs)	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. "Any" is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.	During the 31-day (Days 0-30) follow-up period after the booster dose
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.	During the entire study period starting at the administration of the first vaccine dose up to study end (from Day 0 up to Month 7)
Anti-pneumococcal dPly and PhtD Proteins Antibody Concentrations	Seropositivity status, defined as anti-pneumococcal dPly antibody concentrations ≥ 599 Luminex Units per milliliter (LU/mL) and anti-pneumococcal PhtD antibody concentrations ≥ 391 LU/mL.	One month post-dose 2 (Month 3), prior to the booster dose (Month 6) and one month post-booster (Month 7)
Anti-pneumococcal Serotypes and Cross-reactive Serotypes Antibody Concentrations	Seropositivity status, defined as anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and cross-reactive serotype 6A and 19 antibody concentrations ≥ 0.05 microgram per milliliter (µg/mL).	One month post-dose 2 (Month 3), prior to the booster dose (Month 6) and one month post-booster (Month 7)
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes and Cross-reactive Serotypes	Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and cross-reactive serotypes 6A and 19A ≥ 8.	One month post-dose 2 (Month 3), prior to the booster dose (Month 6) and one month post-booster (Month 7)
Antibody Concentrations to Protein D (Anti-PD)	Seropositivity status, defined as anti-PD antibody concentrations ≥ 112 Luminex Units per milliliter (LU/mL).	One month post-dose 2 (Month 3), prior to the booster dose (Month 6) and one month post-booster (Month 7)
Level of Anti-dPly Antibodies Inhibiting Ply Haemolysis Activity	Inhibition of haemolysis activity of pneumolysin (Ply) by anti-dPly antibodies was measured in vitro by mean of a haemolytic assay. The haemolysis activity could be followed by measuring the level of haemoglobin released. Anti-dPly titers (for inhibition of haemolytic activity) ≥ 140.	One month post-dose 2 (Month 3), prior to the booster dose (Month 6) and one month post-booster (Month 7)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Prymula R, Pazdiora P, Traskine M, Ruggeberg JU, Borys D. Safety and immunogenicity of an investigational vaccine containing two common pneumococcal proteins in toddlers: a phase II randomized clinical trial. Vaccine. 2014 May 23;32(25):3025-34. doi: 10.1016/j.vaccine.2014.03.066. Epub 2014 Apr 1.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2009
• Primary Completion (Actual): October 12, 2010
• Study Completion (Actual): March 2, 2011

Study Registration Dates

• First Submitted: September 24, 2009
• First Submitted That Met QC Criteria: September 24, 2009
• First Posted (Estimate): September 28, 2009

Study Record Updates

• Last Update Posted (Actual): November 5, 2020
• Last Update Submitted That Met QC Criteria: October 15, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: safety; immunogenicity; Pneumococcal vaccine; Streptococcus pneumoniae; Haemophilus influenzae; toddlers; Streptococcus Pneumoniae Vaccines
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 113171; 2009-012701-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• 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; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 113171
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 113171
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 113171
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 113171
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 113171
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register