Immunological Persistence After Priming With GSK1024850A Vaccine and Safety& Immunogenicity After Booster Dose

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01119625
First received: April 22, 2010
Last updated: June 14, 2012
Last verified: June 2012
  Purpose

This primary purpose of this study is the evaluation of the immunological persistence following completion of the 3-dose primary vaccination course with either a clinical or a commercial lot of pneumococcal conjugate vaccine GSK1024850A in study NCT00808444. In addition, the study will also assess the safety, reactogenicity and immunogenicity of a fourth dose of pneumococcal conjugate vaccine GSK1024850A (commercial lot) when co-administered with Infanrix-IPV/Hib at 18-21 months of age in children primed in study NCT00808444.

The primary vaccination study was conducted in Malaysia and Singapore. The booster vaccination study will not be performed in Malaysia since the pneumococcal conjugate vaccine GSK1024850A has been registered in September 2009. However, subjects in Malaysia will be offered a booster dose of the commercial pneumococcal conjugate vaccine licensed in Malaysia and Infanrix-IPV/Hib vaccine during the second year of life according to the nationally recommended regimen. Administration of the booster dose will be outside the set-up of a clinical trial. Hence no data will be collected, no blood samples will be taken in Malaysia.


Condition Intervention Phase
Pneumococcal Disease
Haemophilus Influenzae Infections
Biological: Pneumococcal vaccine GSK1024850A
Biological: Infanrix-IPV/Hib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Evaluation of Immunological Persistence Following 3-dose Priming With GSK Biologicals' 10-valent Pneumococcal Conjugate Vaccine in Study NCT00808444 and Safety and Immunogenicity Following a Booster Dose of the Same Vaccine

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. [ Time Frame: Before booster vaccination at Month 0 ] [ Designated as safety issue: No ]

    Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

    Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL).

    Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.


  • Concentrations of Antibodies Against Protein D (PD). [ Time Frame: Before booster vaccination at Month 0 ] [ Designated as safety issue: No ]
    Anti-PD antibodies were determined using an ELISA assay. Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EU/mL).


Secondary Outcome Measures:
  • Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). [ Time Frame: Within 4 days (Days 0-3) after booster vaccination. ] [ Designated as safety issue: No ]

    Solicited AEs = AEs to be recorded as endpoints in the clinical study. The presence/occurrence/intensity of these events is actively solicited from the subject or an observer during a specified post-vaccination follow-up period.

    Solicited local symptoms assessed 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 above 30 millimetre (mm).


  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). [ Time Frame: Within 4 days (Days 0-3) after booster vaccination. ] [ Designated as safety issue: No ]

    Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (= 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 which 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 = temperature >39.5°C.

    Related = solicited symptom assessed by the investigator as causally related to study vaccination.


  • Number of Subjects Reporting Unsolicited Adverse Events (AEs). [ Time Frame: Within 31 days (Days 0-30) after booster vaccination ] [ Designated as safety issue: No ]
    Unsolicited AEs = Any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.

  • Number of Subjects Reporting Serious Adverse Events (SAEs). [ Time Frame: During the entire study period, from the booster vaccination, at Month 0, up to the study end, at Month 1 ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

  • Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. [ Time Frame: Before and one month after booster vaccination (at Month 0 and Month 1) ] [ Designated as safety issue: No ]
    Opsonophagocytic activity (OPA) testing was not performed.

  • Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A. [ Time Frame: Before and one month after booster vaccination (at Month 0 and Month 1) ] [ Designated as safety issue: No ]
    Opsonophagocytic activity (OPA) testing was not performed.

  • Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. [ Time Frame: Before booster vaccination at Month 0 ] [ Designated as safety issue: No ]

    Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL).

    The antibody concentrations against the cross-reactive pneumococcal serotypes 6A and 19A were determined by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.


  • Concentrations of Antibodies Against Diphtheria and Tetanus. [ Time Frame: Before booster vaccination at Month 0 ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs) in International units per millilitre (IU/mL). The cut-off of the assay was 0.1 IU/mL.

  • Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). [ Time Frame: Before booster vaccination at Month 0 ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EU/mL). The cut-off of the assay was 5 EU/mL.

  • Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). [ Time Frame: Before booster vaccination at Month 0 ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The cut-off of the assay was 0.15 µg/mL.

  • Titers of Antibodies Against Poliovirus Types 1, 2 and 3. [ Time Frame: Before booster vaccination at Month 0 ] [ Designated as safety issue: No ]
    Titers were expresses as geometric mean titers (GMTs). The cut-off of the assay was 8.

  • Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. [ Time Frame: Before and one month after booster vaccination (at Month 0 and Month 1) ] [ Designated as safety issue: No ]

    Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

    Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL).

    Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.


  • Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. [ Time Frame: Before and one month after booster vaccination (at Month 0 and Month 1) ] [ Designated as safety issue: No ]

    Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL).

    The antibody concentrations against the cross-reactive pneumococcal serotypes 6A and 19A were determined by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.


  • Concentrations of Antibodies Against Protein D (PD). [ Time Frame: Before and one month after booster vaccination (at Month 0 and Month 1) ] [ Designated as safety issue: No ]
    Anti-PD antibodies were determined using an ELISA assay. Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EU/mL).

  • Concentrations of Antibodies Against Diphtheria and Tetanus. [ Time Frame: Before and one month after booster vaccination (at Month 0 and Month 1) ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs) in International units per millilitre (IU/mL). The cut-off of the assay was 0.1 IU/mL.

  • Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). [ Time Frame: Before and one month after booster vaccination (at Month 0 and Month 1) ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EU/mL). The cut-off of the assay was 5 EU/mL.

  • Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). [ Time Frame: Before and one month after booster vaccination (at Month 0 and Month 1) ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The cut-off of the assay was 0.15 µg/mL.

  • Titers of Antibodies Against Poliovirus Types 1, 2 and 3. [ Time Frame: Before and one month after booster vaccination (at Month 0 and Month 1) ] [ Designated as safety issue: No ]
    Titers were expresses as geometric mean titers (GMTs). The cut-off of the assay was 8.


Enrollment: 238
Study Start Date: July 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group
children primed with 3 doses of commercial lot of Synflorix™ co-administered with Rotarix™ and Infanrix™-hexa in the primary phase of the study (NCT00808444) and boosted with commercial lot of Synflorix™ co-administered with Infanrix™-IPV/Hib. The Synflorix™ vaccine (commercial lots) was administered intramuscularly in the right deltoid or anterolateral thigh and the Infanrix™-IPV/Hib vaccine was administered intramuscularly in the left deltoid or anterolateral thigh.
Biological: Pneumococcal vaccine GSK1024850A
Intramuscular injection, one dose
Biological: Infanrix-IPV/Hib
Intramuscular injection, one dose
Active Comparator: Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group
children primed with 3 doses of clinical lot of Synflorix™ + Rotarix™ co-administered with Infanrix™-hexa in the primary phase of the study (NCT00808444) and boosted with commercial lot of Synflorix™ co-administered with Infanrix™-IPV/Hib. The Synflorix™ vaccine (clinical and commercial lots) was administered intramuscularly in the right deltoid or anterolateral thigh and the Infanrix™-IPV/Hib vaccine was administered intramuscularly in the left deltoid or anterolateral thigh.
Biological: Pneumococcal vaccine GSK1024850A
Intramuscular injection, one dose
Biological: Infanrix-IPV/Hib
Intramuscular injection, one dose

  Eligibility

Ages Eligible for Study:   18 Months to 21 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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, 18 and 21 months of age at the time of booster vaccination.
  • Subjects who received three doses of pneumococcal conjugate vaccine in study NCT00808444
  • 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 vaccination, 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.
  • Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to vaccination.
  • A family history of congenital or hereditary immunodeficiency.
  • Administration of immunoglobulins and/ or any blood products within the 3 months preceding vaccination or planned use during the study period.
  • Administration of any pneumococcal and/or vaccine containing diphtheria, tetanus, pertussis, poliomyelitis or Haemophilus influenzae type b antigens since the end of study NCT00808444.
  • Planned administration/administration of a vaccine not foreseen by the study protocol during the study period starting from 30 days before vaccination and ending 30 days after vaccination.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • History of any reaction or allergic disease likely to be exacerbated by any component of the study vaccines.
  • Known hypersensitivity to any component of the study vaccines including anaphylactic reactions following the administration of the study vaccines.
  • Major congenital defects or serious chronic illness.
  • History of any neurologic disorders or seizures. (Subjects who have had a single uncomplicated febrile convulsion in the past can be included)
  • Fever at the time of vaccination.

    • Fever is defined as rectal temperature >= 38.0°C or tympanic/axillary/ oral temperature >= 37.5°C.
  • Acute disease at the time of enrolment.

    • Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
  • Child in care.
  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: NCT01119625

Locations
Singapore
GSK Investigational Site
Singapore, Singapore, 688846
GSK Investigational Site
Singapore, Singapore, 229899
GSK Investigational Site
Singapore, Singapore, 119074
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01119625     History of Changes
Other Study ID Numbers: 113266
Study First Received: April 22, 2010
Results First Received: February 16, 2012
Last Updated: June 14, 2012
Health Authority: Singapore: Health Sciences Authority

Keywords provided by GlaxoSmithKline:
safety
Streptococcus pneumoniae
immunogenicity
Pneumococcal conjugate vaccine
Haemophilus influenzae

Additional relevant MeSH terms:
Influenza, Human
Haemophilus Infections
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Pasteurellaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on August 28, 2014