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

Phase 3
Completed
Conditions
Infections, Streptococcal
Streptococcus Pneumoniae Vaccines
Interventions
Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A)
Biological: Infanrix™-IPV/Hib
Registration Number
NCT00609492
Lead Sponsor
GlaxoSmithKline
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
245
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Full term GroupInfanrix™-IPV/HibChildren born after a gestation period of more than 36 weeks
Preterm I GroupGSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A)Children born after a gestation period of 27-30 weeks
Preterm II GroupGSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A)Children born after a gestation period of 31-36 weeks
Full term GroupGSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A)Children born after a gestation period of more than 36 weeks
Preterm I GroupInfanrix™-IPV/HibChildren born after a gestation period of 27-30 weeks
Preterm II GroupInfanrix™-IPV/HibChildren born after a gestation period of 31-36 weeks
Primary Outcome Measures
NameTimeMethod
Number of Subjects Reporting Fever With Rectal Temperature Above (>) 39.0 Degrees Celsius (°C)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
NameTimeMethod
Number of Subjects With Any and Grade 3 Solicited Local SymptomsWithin 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 Seropositive Subjects for Anti-pneumococcal SerotypesPrior 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 SerotypesPrior 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.

Number of Subjects With Unsolicited Adverse Events (AEs)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)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.

Antibody Concentrations Against Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT)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).

Antibody Concentrations Against Anti-polyribosyl-ribitol-phosphate (Anti-PRP)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).

Opsonophagocytic Activity (OPA) Against Pneumococcal SerotypesOne 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 19AOne 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.

Number of Seropositive Subjects for Protein D Antibodies (Anti-PD)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).

Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN AntibodiesOne 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 Seropositive Subjects for Opsonophagocytic Activity (OPA) Against Pneumococcal SerotypesOne 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.

Number of Subjects With Any and Grade 3 Solicited General SymptomsWithin 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 Seropositive Subjects for Pneumococcal Cross-reactive Serotypes 6A and 19APrior 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 Protein D (Anti-PD)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)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).

Number of Seroprotected Subjects Against Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3)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 Concentrations Against Pneumococcal SerotypesPrior 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).

Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19APrior 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 Seroprotected Subjects Against Anti-polyribosyl-ribitol Phosphate (Anti-PRP)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/mLPrior 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).

Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti- Filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN)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 Titers Against Anti-polio Type 1, 2 and 3Prior 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).

Opsonophagocytic Activity (OPA) Against Pneumococcal Cross-reactive Serotypes 6A and 19AOne 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).

Antibody Concentrations Against Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN)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).

Antibody Concentrations Against Anti-hepatitis B Surface Antigen (HBs)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).

Trial Locations

Locations (1)

GSK Investigational Site

🇪🇸

Móstoles/Madrid, Spain

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