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Long-term Follow-up Study of Children Previously Primed With GSK Pneumococcal Vaccine (GSK1024850A) and of Unprimed Children

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00950833
First Posted: August 3, 2009
Last Update Posted: August 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose

The objective of this study is to evaluate the immune memory through the administration of an additional dose of GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A, the antibody persistence and long-term effect on nasopharyngeal carriage of S. pneumoniae and H. influenzae in subjects primed and boosted with GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A in previous primary and booster studies. For subjects that did not receive the investigational vaccine during the primary and booster study, the objective is to evaluate immunogenicity, safety and reactogenicity of a 2-dose catch-up vaccination with GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A.

This protocol posting deals with objectives & outcome measures of the extension phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT00370318). The objectives & outcome measures of the booster phase are presented in a separate protocol posting (NCT00496015).


Condition Intervention Phase
Infections, Streptococcal Biological: Pneumococcal vaccine GSK1024850A Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Vaccination Course in Children Primed and Boosted With Pneumococcal Vaccine GSK 1024850A and in Age-matched Unprimed Children

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Antibody Concentrations Against Vaccine Pneumococcal Serotypes [ Time Frame: At 7-10 days after the first vaccine dose ]
    Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition enzyme linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.05 μg/mL.


Secondary Outcome Measures:
  • Antibody Concentrations Against Vaccine Pneumococcal Serotypes [ Time Frame: Prior to the first study vaccine dose (At Day 0) ]
    Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition ELISA, presented as GMCs and expressed in μg/mL. The seropositivity cut-off value of the assay was an antibody concentration ≥ 0.05 μg/mL.

  • Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes [ Time Frame: Prior to (Day 0) and 7-10 days after the first vaccine dose ]
    Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes ≥ the value of 8, presented as geometric mean titers (GMTs). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -6B, -7F, -9V, -14, -18C, -19F and -23F).

  • Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A [ Time Frame: Prior to (Day 0) and 7-10 days after the first vaccine dose ]
    The vaccine pneumococcal cross-reactive serotypes 6A and 19A have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.

  • Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A [ Time Frame: Prior to (Day 0) and 7-10 days after the first vaccine dose ]
    Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (Opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs).

  • Antibody Concentrations Against Protein D (Anti-PD) [ Time Frame: Prior to (Day 0) and 7-10 days after the first vaccine dose ]
    Anti-protein D (anti-PD) concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value of the assay was an antibody concentration ≥ 100 EL.U/mL.

  • Memory B-cell Detection for Vaccine Polysaccharides (PS) [ Time Frame: Prior to (Day 0) and 7-10 days after the first vaccine dose ]
    B-cell detection for the pneumococcal serotype specific polysaccharides (1, 5, 6B, 18C, 19F, 23F and C) was tabulated for a subset of subjects from each group. The results are expressed as the frequencies of antigen-specific memory B-cells within the total memory B-cell population.

  • Antibody Concentrations Against Vaccine Pneumococcal Serotypes [ Time Frame: At Month 12, one month after the second vaccine dose ]
    The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs), expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.

  • Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes [ Time Frame: At Month 12, one month after the second vaccine dose ]
    Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes ≥ the value of 8, presented as geometric mean titers (GMTs). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -6B, -7F, -9V, -14, -18C, -19F and -23F).

  • Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A [ Time Frame: At Month 12, one month after the second vaccine dose ]
    The vaccine pneumococcal cross-reactive serotypes 6A and 19A have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.

  • Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A [ Time Frame: At Month 12, one month after the second vaccine dose ]
    Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs).

  • Antibody Concentrations Against Protein D (Anti-PD) [ Time Frame: At Month 12, one month after the second vaccine dose ]
    Anti-protein D (anti-PD) concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value of the assay was an antibody concentration ≥ 100 EL.U/mL.

  • Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) [ Time Frame: At 25-36 months post-vaccination in previous 107137 (NCT00496015) study ]
    The Neisseria meningitidis serogroups assessed using rabbit complement were: A, C, W-135 and Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY), presented as geometric mean titers (GMTs). The seropositivity cut-off of the assay was an antibody titer ≥ 8.

  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 4-day (Days 0-3) post-vaccination period ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. This outcome measure refers only to the primed groups.

  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 4-day (Days 0-3) post-vaccination period following each dose and across doses ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. This outcome measure refers only to the unprimed group.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 4-day (Days 0-3) post-vaccination period ]
    Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as causally related to study vaccination. This outcome measure refers only to the primed groups.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 4-day (Days 0-3) post-vaccination period following each dose and across doses ]
    Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as causally related to study vaccination. This outcome measure refers only to the unprimed group.

  • Number of Subjects With Any Unsolicited Adverse Events (AEs) [ Time Frame: Within 31 days (Days 0-30) after each vaccination ]
    An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (from Day 0 up to Month 10 or Month 12) ]
    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 Nasopharyngeal Swabs With Streptococcus Pneumoniae (Vaccine Serotypes) [ Time Frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age ]
    Positive cultures of S. pneumoniae Synflorix™ vaccine serotypes identified in the nasopharynx were recorded and the percentage of subjects with positive nasopharyngeal samples was calculated.

  • Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes) [ Time Frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age ]
    Positive cultures of S. pneumoniae cross- reactive serotypes identified in the nasopharynx were recorded and the percentage of subjects with positive nasopharyngeal samples was calculated.

  • Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) [ Time Frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age ]
    Positive cultures of S. pneumoniae non- Synflorix™ vaccine, non-cross-reactive serotypes identified in the nasopharynx were recorded and the percentage of subjects with positive nasopharyngeal samples was calculated.

  • Number of Nasopharyngeal Swabs With Haemophilus Influenzae [ Time Frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age ]
    Positive cultures of H. influenzae identified in the nasopharynx were recorded and the percentage of subjects with positive nasopharyngeal samples was calculated.

  • Number of Subjects With New Acquisition of S. Pneumoniae (Vaccine Serotypes) in Nasopharyngeal Swabs [ Time Frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age ]
    Frequency of acquisition of new Synflorix™ vaccine serotypes in the nasopharynx was done per group at the same swab time-point.

  • Number of Subjects With New Acquisition of S. Pneumoniae (Cross-reactive Serotypes) in Nasopharyngeal Swabs [ Time Frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age ]
    Frequency of acquisition of new cross-reactive serotypes in the nasopharynx was done per group at the same swab time-point.

  • Number of Subjects With New Acquisition of S. Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) in Nasopharyngeal Swabs [ Time Frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age ]
    Frequency of acquisition of new non- vaccine, non-cross-reactive serotypes in the nasopharynx was done per group at the same swab time-point.

  • Number of Subjects With New Acquisition of H. Influenzae in Nasopharyngeal Swabs [ Time Frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age ]
    Frequency of acquisition of new H. influenzae strains in the nasopharynx was done per group at the same swab time-point.


Enrollment: 467
Actual Study Start Date: August 10, 2009
Study Completion Date: October 27, 2010
Primary Completion Date: September 16, 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: AP-AP Group
subjects from the AP-AP group, previously vaccinated with pneumococcal conjugate vaccine GSK1024850A in study NCT00496015, receiving an additional dose of pneumococcal conjugate vaccine GSK1024850A for immune memory assessment
Biological: Pneumococcal vaccine GSK1024850A
1 or 2 intramuscular injections
Active Comparator: NAP-pre Group
subjects from the NAP-pre group, previously vaccinated with pneumococcal conjugate vaccine GSK1024850A in study NCT00496015 receiving an additional dose of pneumococcal conjugate vaccine GSK1024850A for immune memory assessment
Biological: Pneumococcal vaccine GSK1024850A
1 or 2 intramuscular injections
Active Comparator: Unprimed Group
Age-matched subjects from the unprimed group of the NCT00496015 study, not previously vaccinated with any pneumococcal vaccine, receiving two doses of pneumococcal conjugate vaccine GSK1024850A
Biological: Pneumococcal vaccine GSK1024850A
1 or 2 intramuscular injections

Detailed Description:
This protocol posting has been updated according to Protocol Amendment 1, July 2009
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   31 Months to 44 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, 31 and 34 months of age at the time of the enrolment.
  • Subjects who previously participated in study NCT00496015
  • For the subjects in the primed AP-AP and NAP-pre groups: subjects who received a booster dose of the pneumococcal conjugate vaccine prior to the study amendment 3.
  • For the subjects in the unprimed group: subjects who received a dose of the meningococcal vaccine GSK134612.
  • 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:

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding enrolment, or planned use during the entire study period.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs during the entire study period.
  • Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before each dose of study vaccine and ending 30 days after.
  • 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).
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
  • History of seizures or progressive neurological disease.
  • Acute disease at the time of enrolment, defined as the presence of a mild, moderate or severe illness with or without fever.
  • Administration or planned use of immunoglobulins and/ or any blood products during the entire study period.
  • A family history of congenital or hereditary immunodeficiency.
  • Major congenital defects or serious chronic illness.
  • Subjects of which both parents have a history of atopia (polinosis, asthma, atopic eczema).
  • Administration of any pneumococcal vaccine since the end of study NCT00496015.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00950833


Locations
Czechia
GSK Investigational Site
Brno, Czechia, 628 00
GSK Investigational Site
Hradec Kralove, Czechia, 500 01
GSK Investigational Site
Jindrichuv Hradec, Czechia, 377 01
GSK Investigational Site
Nachod, Czechia, 547 01
GSK Investigational Site
Ostrava, Czechia, 70800
GSK Investigational Site
Pardubice, Czechia, 532 03
GSK Investigational Site
Praha 5, Czechia, 150 00
GSK Investigational Site
Praha 6, Czechia, 160 00
GSK Investigational Site
Praha 9, Czechia, 190 00
GSK Investigational Site
Znojmo, Czechia, 669 00
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Publications:
Prymula R et al. Immune memory 2-3 years after vaccination with pneumococcal non-typeable Heamophilus influenzae protein-D conjugate vaccine (PHiD-CV), with or without prophylactic paracetamol. Abstract presented at the 30th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID), Thessaloniki, Greece, 8-12 May 2012.
Prymula R et al. Long-term effect of 10-valent pneumococcal non-typeable Haemophilus Influenzae protein D conjugate vaccine (PHiD-CV) on nasopharyngeal bacterial carriage in Czech children. Abstract presented at the 8th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD), Iguaçu Falls, Brazil, 11-15 March, 2012.
Silfverdal SA et al. Immunogenicity and reactogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus Influenzae protein D conjugate vaccine (PHiD-CV) during the fourth year of life. Abstract presented at the 8th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD), Iguaçu Falls, Brazil, 11-15 March, 2012.

Study Data/Documents: Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 112801
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 112801
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 112801
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: 112801
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: 112801
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: 112801
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: 112801
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00950833     History of Changes
Other Study ID Numbers: 112801
First Submitted: July 30, 2009
First Posted: August 3, 2009
Results First Submitted: April 18, 2017
Results First Posted: August 7, 2017
Last Update Posted: August 7, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
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.

Keywords provided by GlaxoSmithKline:
Catch-up vaccination
Pneumococcal vaccine
Immune memory
Nasopharyngeal carriage
Immunogenicity
Pneumococcal disease
Safety

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