This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Evaluate Safety and Immunogenicity of a Booster Dose of Pneumococcal Conjugate Vaccine in Preterm Born Infants.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00609492
First received: January 25, 2008
Last updated: March 1, 2017
Last verified: March 2017
  Purpose

The purpose of this study is to evaluate the safety, reactogenicity and immunogenicity of a booster dose of GlaxoSmithKline (GSK) Biologicals´ pneumococcal conjugate vaccine co-administered with a booster dose of DTPa-IPV/Hib (Infanrix-IPV/Hib) in preterm born children at the age of 16-18 months. This protocol posting deals with objectives & outcome measures of the booster phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number =NCT00390910 ). Subjects participating in this study should have received three doses of pneumococcal vaccine in the primary study.

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


Condition Intervention Phase
Infections, Streptococcal Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A) Biological: Infanrix™-IPV/Hib Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Prevention
Official Title: Safety, Reactogenicity and Immunogenicity Following Booster Dose of GSK Biologicals´ Pneumococcal Conjugate Vaccine When Co-administered With a Booster Dose of Infanrix-IPV/Hib in Preterm Born Children at 16-18 Months of Age

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects Reporting Fever With Rectal Temperature Above (>) 39.0 Degrees Celsius (°C) [ Time Frame: Within 4-days (Day 0-3) after booster vaccination ]
    Fever was measured as rectal temperature. Assessment of occurrences of fever > 39.0 °C was performed within 4-days (Day 0-3) after booster vaccination of Synflorix™ and Infanrix™-IPV/Hib vaccine.


Secondary Outcome Measures:
  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: Within 4-days (Day 0-3) after booster vaccination ]
    Solicited local symptoms assessed included 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.

  • Number of Subjects With Any and Grade 3 Solicited General Symptoms [ Time Frame: Within 4-days (Day 0-3) after booster vaccination ]
    Solicited general symptoms assessed included drowsiness, fever (defined as rectal temperature ≥ 38.0°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 (rectal temperature) above (>) 40.0 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.

  • Number of Subjects With Unsolicited Adverse Events (AEs) [ Time Frame: Within 31-days (Day 0-30) after booster vaccination ]
    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 as incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: Throughout the active phase of the study (Month 0 to Month 1) ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: Throughout the entire study period starting from Month 0 up to the end of the extended safety follow-up (Month 6) ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  • Number of Seropositive Subjects for Anti-pneumococcal Serotypes [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™ -IPV/Hib vaccine ]
    A seropositive subject was defined as a subject who had the anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C , 19F and 23F concentrations greater than or equal to (≥) the cut-off value of 0.05 micrograms per milliliter (μg/mL).

  • Number of Seroprotected Subjects Against Anti-pneumococcal Serotypes [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    A seroprotected subjects was defined as a subject who had anti-pneumococcal serotypes antibody concentrations greater than or equal to (≥) the threshold value of 0.20 micrograms per milliliter (μg/mL). The anti-pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

  • Antibody Concentrations Against Pneumococcal Serotypes [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    Seropositivity status was defined as the anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations greater than or equal to (≥) the cut-off value of 0.05 micrograms per milliliter (µg/mL). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs).

  • Number of Seropositive Subjects for Pneumococcal Cross-reactive Serotypes 6A and 19A [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™ -IPV/Hib vaccine ]
    A seropositive subject was defined as a subject who had the anti-pneumococcal serotypes 6A and 19A concentrations greater than or equal to (≥) the cut-off value of 0.05 micrograms per milliliter (μg/mL).

  • Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    Seropositivity status was defined as the anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations greater than or equal to (≥) the cut-off value of 0.05 micrograms per milliliter (µg/mL). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs).

  • Number of Seropositive Subjects for Protein D Antibodies (Anti-PD) [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    A seropositive subject was defined as a subject who had anti-PD concentration greater than or equal to (≥) the value of 100 ELISA units per milliliter (EL.U/mL).

  • Antibody Concentrations Against Protein D (Anti-PD) [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    Seropositivity status was defined as the anti-protein D (Anti-PD) antibody concentrations greater than or equal to (≥) 100 ELISA units per milliliter (EL.U/mL). Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs).

  • Number of Seroprotected Subjects Against Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    A seroprotected subject was defined as a subject who had anti-DT and anti-TT concentrations greater than or equal to (≥) the value of 0.1 international units per milliliter (IU/mL).

  • Antibody Concentrations Against Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    Seropositivity status was defined as the anti-diphtheria toxoid (Anti-DT) and anti-tetanus toxoid (Anti-TT) antibody concentrations greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs).

  • Number of Seroprotected Subjects Against Anti-polyribosyl-ribitol Phosphate (Anti-PRP) [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    A seroprotected subject was defined as a subject who had anti-PRP concentrations greater than or equal to (≥) the value of 0.15 micrograms per milliliter (µg /mL).

  • Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration ≥ 1.0 µg/mL [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    The concentration of anti-polyribosyl-ribitol phosphate (Anti-PRP) antibody assessed was greater than or equal to (≥) the value of 1.0 micrograms per milliliter (µg /mL).

  • Antibody Concentrations Against Anti-polyribosyl-ribitol-phosphate (Anti-PRP) [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™ -IPV/Hib vaccine ]
    Seropositivity status was defined as the anti-polyribosyl-ribitol-phosphate (Anti-PRP) antibody concentrations greater than or equal to (≥) 0.15 micrograms per milliliter (µg /mL) and ≥ 1.0 µg/mL. Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs).

  • Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti- Filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    A seropositive subject was defined as a subject who had anti-PT, anti-FHA and anti-PRN concentrations greater than or equal to (≥) the value of 5 ELISA units per milliliter (EL.U/mL).

  • Antibody Concentrations Against Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    Seropositivity status was defined as the anti-pertussis toxoid (Anti-PT), anti-filamentous haemagglutinin (Anti-FHA) and anti-pertactin (Anti-PRN) antibody concentrations greater than or equal to (≥) 5 ELISA units per milliliter (EL.U /mL). Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs).

  • Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies [ Time Frame: One month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    Vaccine response was defined as antibody concentrations ≥ 5 EL.U/mL at post-booster, for initially seronegative subjects (S-) (with concentrations < 5 EL.U/mL) and for initially seropositive subjects (S+) (with concentrations ≥ 5 EL.U/mL), antibody concentrations at post-booster ≥ 2 fold the pre-vaccination antibody concentration.

  • Number of Seroprotected Subjects Against Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    A seroprotected subject was defined as a subject who had anti-polio types 1, 2 and 3 titers greater than or equal to (≥) the value of 8.

  • Antibody Titers Against Anti-polio Type 1, 2 and 3 [ Time Frame: Prior to (Pre-booster) and one month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    Seroprotection status was defined as the anti-polio type 1, anti-polio type 2 and anti-polio type 3 antibody titers greater than or equal to (≥) the cut-off value of 8, presented as geometric mean titers (GMTs).

  • Antibody Concentrations Against Anti-hepatitis B Surface Antigen (HBs) [ Time Frame: Prior to (Pre-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    Seroprotection status was defined as the Anti-HBs antibody concentrations greater than or equal to (≥) 10 milli international units per milliliter (mIU/mL), presented as geometric mean concentrations (GMCs).

  • Number of Seropositive Subjects for Opsonophagocytic Activity (OPA) Against Pneumococcal Serotypes [ Time Frame: One month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    A seropositive subject was defines as a subject with opsonophagocytic activity cut-off value greater than or equal to (≥) the value of 8. The vaccine pneumococcal serotypes investigated were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

  • Opsonophagocytic Activity (OPA) Against Pneumococcal Serotypes [ Time Frame: One month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F, with a cut-off value greater than or equal to (≥) 8, presented as geometric mean titers (GMTs).

  • Number of Seropositive Subjects for Opsonophagocytic Activity (OPA) Against Pneumococcal Cross-reactive Serotypes 6A and 19A [ Time Frame: One month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    A seropositive subject was defined as a subject with opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A greater than or equal to (≥) the cut-off value of 8.

  • Opsonophagocytic Activity (OPA) Against Pneumococcal Cross-reactive Serotypes 6A and 19A [ Time Frame: One month after (Post-booster) the administration of the booster dose of Synflorix™ vaccine co-administered with the booster dose of Infanrix™-IPV/Hib vaccine ]
    Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal cross-reactive serotypes 6A and 19A, with a cut-off value greater than or equal to (≥) 8, presented as geometric mean titers (GMTs).


Enrollment: 245
Study Start Date: January 2008
Study Completion Date: March 2009
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Preterm I Group
Children born after a gestation period of 27-30 weeks
Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A)
Single dose, intramuscular injection
Biological: Infanrix™-IPV/Hib
Single dose, intramuscular injection
Experimental: Preterm II Group
Children born after a gestation period of 31-36 weeks
Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A)
Single dose, intramuscular injection
Biological: Infanrix™-IPV/Hib
Single dose, intramuscular injection
Active Comparator: Full term Group
Children born after a gestation period of more than 36 weeks
Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A)
Single dose, intramuscular injection
Biological: Infanrix™-IPV/Hib
Single dose, intramuscular injection

  Eligibility

Ages Eligible for Study:   16 Months to 18 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
  • A male or female between, and including, 16-18 months of age at the time of the booster vaccination.
  • A male or female who previously participated in study 107737 and received three doses of pneumococcal conjugate vaccine.
  • Written informed consent obtained from the parent or guardian of the subject.
  • Free of obvious health problems as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

  • Concurrently participating in another clinical study, at any time during the study period (active phase and extended safety follow-up), in which the subject has been or will be exposed to an investigational or a non-investigational product.
  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the booster dose of study vaccines, or planned use during the study period (active phase and 5 months extended safety follow-up).
  • Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the booster dose of study vaccine.
  • Planned administration/administration of a vaccine not foreseen by the study protocol, during the period starting from one month (30 days) before the booster dose of study vaccines (Visit 1) and up to the follow-up visit (Visit 2).
  • Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae other than the study vaccines from study 107737
  • History of or intercurrent diphtheria, tetanus, hepatitis B, pertussis, polio, Haemophilus influenzae type b disease.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
  • History of seizures or progressive neurological disease
  • Acute disease at the time of enrolment.
  • Febrile illness defined as oral, axillary or tympanic temperature < 37.5°C / rectal temperature < 38°C. A temperature greater than or equal to these cut-offs warrants deferral of the vaccination pending recovery of the subject.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
  • A family history of congenital or hereditary immunodeficiency.
  • Major congenital defects or serious chronic illness.
  • Administration of immunoglobulins, with the exception of monoclonal antibodies against RSV, and/or any blood products within three months preceding the booster dose of study vaccines or planned administration during the active phase of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00609492

Locations
Greece
GSK Investigational Site
Athens, Greece, 115 27
GSK Investigational Site
Athens, Greece, 11527
GSK Investigational Site
Ioannina, Greece, 452 21
GSK Investigational Site
Thessaloniki, Greece, 54636
Spain
GSK Investigational Site
Burgos, Spain, 09005
GSK Investigational Site
Madrid, Spain, 28047
GSK Investigational Site
Móstoles/Madrid, Spain, 28935
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Publications:
Omenaca F et al. Booster vaccination of preterm-born children with 10-valent pneumococcal non-typeable haemophilus influenzae protein D-conjugate vaccine (PHiD-CV): antibody responses and safety. Abstract presented at the 6th World Congress of the World Society for Pediatric Infectious Diseases (WSPID). Beunos Aires, Argentina, 18-22 November 2009.
Omenaca F et al. Immunogenicity and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) following primary and booster vaccination in preterm-born children. Abstract presented at Excellence In Paediatrics. Florence, Italy, 3-6 December 2009.

Study Data/Documents: Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 109621
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 109621
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 109621
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 109621
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 109621
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 109621
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 109621
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00609492     History of Changes
Other Study ID Numbers: 109621
Study First Received: January 25, 2008
Results First Received: November 28, 2016
Last Updated: March 1, 2017
Individual Participant Data  
Plan to Share IPD: Yes
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.

Additional relevant MeSH terms:
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 28, 2017