Primary Vaccination Course in Children Receiving Pneumococcal Conjugate Vaccine GSK 1024850A or Prevenar™ and Hiberix™

Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A or Prevenar™ Co-administered With Hiberix™

The purposes of this study are:

To demonstrate the immunogenicity in terms of antibody response following primary vaccination of Korean infants with the pneumococcal conjugate vaccine GSK 1024850A compared to Prevenar™ when co-administered with a Haemophilus influenzae type b (Hib) vaccine in children during the first 6 months of life.

To evaluate the safety/reactogenicity in terms of solicited and unsolicited symptoms and serious adverse events following primary vaccination of Korean infants with the pneumococcal conjugate vaccine GSK 1024850A.

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: Pneumococcal vaccine GSK1024850A (Synflorix); Biological: GSK Biologicals' Hiberix™; Biological: Prevenar

Detailed Description

Vaccination course at 2, 4, 6 months of age.

• Study Type: Interventional
• Enrollment (Actual): 503
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Ansan, Korea, Republic of, 425-707
    • GSK Investigational Site
  • Bucheon-si,, Korea, Republic of, 420-767
    • GSK Investigational Site
  • Daejeon, Korea, Republic of, 301-723
    • GSK Investigational Site
  • Gyeongnam, Korea, Republic of, 641-560
    • GSK Investigational Site
  • Iksan, Korea, Republic of, 570-711
    • GSK Investigational Site
  • Jeju, Korea, Republic of, 690-716
    • GSK Investigational Site
  • Jeonju Jeonbuk, Korea, Republic of, 561-712
    • GSK Investigational Site
  • Pusan, Korea, Republic of, 602-739
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 150-719
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 130-702
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 158-710
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 411-706
    • GSK Investigational Site
  • Suwon City, Korea, Republic of, 442-723
    • GSK Investigational Site
  • Wonju-si Kangwon-do, Korea, Republic of, 220-701
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects between, and including 6-12 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 should be enrolled in the study.
• Written and signed informed consent obtained from the parent(s)/guardian(s) of the child/ward.
• Free of any known or suspected 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, with a birth weight of at least 2.5 kilogram.

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.
• 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 (pharmaceutical product or device).
• Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
• Planned administration/administration of a vaccine not allowed by the study protocol during the study period. Vaccines included in the Korean routine immunization schedule can be administered at least one week before or at least one month after the administration of the study vaccines. Recommended live vaccines not included in the Korean routine immunization schedule can be given at least one month before or at least one month after the administration of the study vaccines.
• 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 (Hepatitis B immunoglobulins at birth are allowed).
• Previous vaccination against Streptococcus pneumoniae and/or Haemophilus influenzae type b.
• History of, or intercurrent Streptococcus pneumoniae and/or Haemophilus influenzae type b disease.
• 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. Study entry should be delayed until the illness has improved.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Synflorix Group; Subjects received 3 doses of Synflorix vaccine co-administered with Hiberix vaccine at Study Months 0, 2 and 4.	Biological: Pneumococcal vaccine GSK1024850A (Synflorix); 3 doses administered intramuscularly.; Biological: GSK Biologicals' Hiberix™; 3 doses administered intramuscularly.; Other Names: Hib
ACTIVE_COMPARATOR: Prevenar Group; Subjects received 3 doses of Prevenar vaccine co-administered with Hiberix vaccine at Study Months 0, 2 and 4.	Biological: GSK Biologicals' Hiberix™; 3 doses administered intramuscularly.; Other Names: Hib; Biological: Prevenar; 3 doses administered intramuscularly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Vaccine Pneumococcal Serotypes Antibody Concentrations Above the Cut-Off Value	Anti-pneumococcal antibody cut-off value assessed was 0.20 microgram per milliliter (ug/mL). The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.	One month after administration of 3rd dose of the pneumococcal conjugate vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With a Seropositivity Status Against Protein D and Defined Pneumococcal Serotypes	Seropositivity status for protein D is defined as anti protein D (anti-PD) antibody concentrations >= 100 Enzyme-Linked Immuno Sorbent Assay (EL) units EL.U/mL. Seropositivity status for pneumococcal serotypes is defined as anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations >= 0.05 ug/mL.	One month after the administration of the 3rd vaccine dose of the pneumococcal conjugate vaccine
Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes Contained in the Vaccine Above the Cut-off Value	The results were presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. In this assay the cut-off value for opsonophagocytic activity against pneumococcal antibody assessed was >= 8. The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.	One month after the administration of the 3rd vaccine dose of the pneumococcal conjugate vaccine
Number of Subjects With Cross-reactive Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value	Anti-pneumococcal antibody cut-off value assessed was 0.20 microgram per milliliter (ug/mL). Pneumococcal cross-reactive serotypes were 6A and 19A.	One month after the administration of the 3rd vaccine dose of the pneumococcal conjugate vaccine
Antibody Concentrations Against Pneumococal Serotypes Contained in the Vaccine	Concentrations are reported as Geometric Mean Concentrations in ug/mL. Pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.	One month after the administration of the 3rd vaccine dose of the pneumococcal conjugate vaccine
Anti-PD Antibody Concentration	Concentration of anti-PD antibody given as GMC expressed in EL.U/mL.	One month after administration of 3rd vaccine dose of the pneumococcal conjugate vaccine
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes	Concentration of cross-reactive pneumococcal serotypes 6A and 19A in ug/mL.	One month after the administration of the 3rd vaccine dose of the pneumococcal conjugate vaccine
Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes	The results were presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. In this assay the cut-off value for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A was defined as >= 8.	One month after the administration of the 3rd vaccine dose of the pneumococcal conjugate vaccine
Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations	Concentration of anti-PRP antibody given as GMC in ug/mL.	One month after the administration of the 3rd vaccine dose of the pneumococcal conjugate vaccine
Number of Subjects With Seroprotection Status Against PRP	Seroprotection status is defined as anti-PRP antibody concentrations above 0.15 ug/mL and above 1.0 ug/mL	One month after the administration of the 3rd vaccine dose of the pneumococcal conjugate vaccine
Number of Subjects Reporting Solicited Local Symptoms	Solicited local symptoms assessed include pain, redness and swelling.	Within 4 days after each vaccination
Number of Subjects With Solicited General Symptoms	Solicited general symptoms assessed include drowsiness, fever, irritability and loss of appetite. Fever was defined as axillary temperature >= 37.5 degrees Celsius.	Within 4 days after each vaccination
Number of Subjects Reporting Unsolicited Adverse Events		Within 31 days after each vaccination
Number of Subjects With 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.	Following the administration of the first dose of the study vaccines throughout the entire study period up to study month 5

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Kim CH, Kim JS, Cha SH, Kim KN, Kim JD, Lee KY, Kim HM, Kim JH, Hyuk S, Hong JY, Park SE, Kim YK, Kim NH, Fanic A, Borys D, Ruiz-Guinazu J, Moreira M, Schuerman L, Kim KH. Response to primary and booster vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in Korean infants. Pediatr Infect Dis J. 2011 Dec;30(12):e235-43. doi: 10.1097/INF.0b013e31822a8541.
• Kim CH et al. Immunogenicity and safety of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Korean children. Abstract presented at the Korean Society of Pediatric Infectious Diseases - 2011 Spring Conference. Seoul, South Korea, 7-11 June 2011.
• Kim CH et al. Immunogenicity of a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and co-administered vaccines following primary vaccination in Asian infants. Abstract presented at the 5th Asian Congress of Pediatric Infectious Diseases (ACPID). Taipei, Taiwan, 23-26 September 2010.
• Kim JS et al. Safety and reactogenicity of primary vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Korean infants. Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Kim KH et al. Immunogenicity of primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Korean infants. Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Schuerman L, Wysocki J, Tejedor JC, Knuf M, Kim KH, Poolman J. Prediction of pneumococcal conjugate vaccine effectiveness against invasive pneumococcal disease using opsonophagocytic activity and antibody concentrations determined by enzyme-linked immunosorbent assay with 22F adsorption. Clin Vaccine Immunol. 2011 Dec;18(12):2161-7. doi: 10.1128/CVI.05313-11. Epub 2011 Oct 12.
• Schuerman L et al. Immune responses against cross-reactive pneumococcal serotypes 6A and 19A with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Schuerman L et al. OPA assay is more reliable predictor of vaccine effectiveness against invasive pneumococcal disease (IPD) than ELISA antibody measurements. Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Schuerman L et al. Population variability in antibody responses following pneumococcal conjugate vaccination: experience with the non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Schuerman L et al. Population variability of opsonophagocytic activity following 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate (PHiD-CV) vaccination more limited than antibody responses. Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.

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): June 10, 2008
• Primary Completion (ACTUAL): May 8, 2009
• Study Completion (ACTUAL): May 8, 2009

Study Registration Dates

• First Submitted: May 16, 2008
• First Submitted That Met QC Criteria: May 19, 2008
• First Posted (ESTIMATE): May 20, 2008

Study Record Updates

• Last Update Posted (ACTUAL): June 8, 2018
• Last Update Submitted That Met QC Criteria: May 9, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Streptococcus pneumoniae; pneumococcal conjugate vaccine
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 110808

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.

Study Data/Documents

1. Study Protocol
   Information identifier: 110808
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 110808
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 110808
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 110808
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 110808
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 110808
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: 110808
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register