Immunogenicity, Safety and Reactogenicity Study of GSK Biologicals' Pneumococcal Vaccine (Synflorix™) When Administered to Children Who Are at an Increased Risk of Pneumococcal Infection
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Infections, Streptococcal
- Sponsor
- GlaxoSmithKline
- Enrollment
- 52
- Locations
- 1
- Primary Endpoint
- Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the immunogenicity, safety and reactogenicity of GSK Biologicals' 10Pn-PD-DiT vaccine in children aged between 2 and 17 years of age having asplenia, splenic dysfunction or complement deficiencies.
In addition, this study will include an age-matched control group of healthy children aged 24-59 months in order to descriptively compare the immunogenicity of 10Pn-PD-DiT vaccine in the at-risk population to that of the general, healthy population one month after each pneumococcal vaccination.
Detailed Description
The protocol has been amended to clarify the definition of priming status to consider for inclusion of subjects in the primed groups.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] can and will comply with the requirements of the protocol.
- •Written informed consent obtained from the parent(s)/LAR(s) of the subject and informed assent obtained from the subject, if appropriate, prior to enrollment.
- •Female subjects of non-child bearing potential may be enrolled in the study. (Non-child bearing potential is defined as pre-menarche, current tubal ligation, hysterectomy or ovariectomy).
- •Female subjects of child bearing potential may be enrolled in the study, if the subject:
- •has practiced adequate contraception for 30 days prior to the first vaccination, and
- •has a negative pregnancy test on the day of vaccination, and
- •has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
- •Priming status:
- •Children who have not been previously vaccinated with any pneumococcal vaccine, i.e. either plain polysaccharide pneumococcal vaccine, Synflorix (10Pn-PD-DiT), Prevenar or Prevenar13 will be considered for inclusion in the unprimed groups.
- •Children who have been previously vaccinated with:
Exclusion Criteria
- •Child in care.
- •Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
- •Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of vaccine(s) and ending 30 days after\*.
- •\* In case an emergency mass vaccination for an unforeseen public health threat is organised by the public health authorities, outside the routine immunization program, vaccines can be administered at any time during the study period provided it is licensed and used according to its Summary of Product Characteristics or Prescribing Information and according to the local governmental recommendations and that a written approval of the Sponsor is provided. Vaccines that are recommended for subjects with an increased risk of bacterial infection, can be administered at any time to the subjects enrolled in the At-risk group.
- •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).
- •History of any neurological disorders or seizures.
- •Acute disease and/or fever at the time of enrollment.
- •History of chronic alcohol consumption and/or drug abuse.
- •Any confirmed or suspected Human Immunodeficiency virus (HIV) infection, based on medical history and physical examination.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
Outcomes
Primary Outcomes
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.
Time Frame: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.
Time Frame: One month after Dose 1 (At Month 1)
Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per millilitre (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. Antibody concentrations \< 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Concentrations of Antibodies Against Protein D (PD) in the At Risk Primed Group.
Time Frame: One month after Dose 1 (At Month 1)
Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per millilitre (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 153 EL.U/mL. Antibody concentrations \< 153 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.
Time Frame: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per millilitre (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. Antibody concentrations \< 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.
Time Frame: One month after Dose 1 (At Month 1)
Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
Concentrations of Antibodies Against Protein D (PD) in the At Risk Unprimed Group.
Time Frame: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per millilitre (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 153 EL.U/mL. Antibody concentrations \< 153 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Secondary Outcomes
- Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 2 for Subjects Aged Between 2 to 4 Years.(During the 4-day (Days 0-3) after dose 2)
- Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 1 for Subjects Aged Between 5 to 17 Years.(During the 4-day (Days 0-3) after dose 1)
- Number of Subjects With Unsolicited AEs.(Within the 31-day (Days 0-30) post- vaccination period)
- Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 1 for Subjects Aged Between 5 to 17 Years.(During the 4-day (Days 0-3) after dose 1)
- Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 2 for Subjects Aged Between 5 to 17 Years.(During the 4-day (Days 0-3) after dose 2)
- Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 2 for Subjects Aged Between 2 to 4 Years.(During the 4-day (Days 0-3) after dose 2)
- Number of Subjects With Serious Adverse Events (SAEs).(From Dose 1 at Month 0 up to study end at Month 1 for primed subjects and at Month 3 for unprimed subjects.)
- Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 1 for Subjects Aged Between 2 to 4 Years.(During the 4-day (Days 0-3) after dose 1)
- Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the Healthy Un-primed Group.(One month after Dose 1 (At Month 1) and/or one month after Dose 2 (At Month 3))
- Concentrations of Antibodies Against Protein D (PD) in the Healthy Unprimed Group.(One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3))
- Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 2 for Subjects Aged Between 5 to 17 Years.(During the 4-day (Days 0-3) after dose 2)
- Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 1 for Subjects Aged Between 2 to 4 Years.(During the 4-day (Days 0-3) after dose 1)
- Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the Healthy Un-primed Group.(One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3))