Booster and Catch-up Vaccination With Vaccine GSK1024850A

Booster Vaccination With Pneumococcal Vaccine GSK1024850A in Primed Children and Catch-up Vaccination in Unprimed Children

The purpose of this study is to evaluate the immunogenicity, safety and reactogenicity of a booster dose of pneumococcal vaccine GSK1024850A administered either at 9-18 months or 15-18 months of age in children primed in primary study NCT00814710.

This study also aims to assess the persistence of antibodies induced following primary vaccination with pneumococcal vaccine GSK1024850A in primary study NCT00814710 prior to booster vaccination and following vaccination in the present study at approximately 24 months of age.

The study is also designed to evaluate the immunogenicity, safety and reactogenicity of pneumococcal vaccine GSK1024850A when administered as a catch-up vaccination (2+1) in the second year of life in children unprimed with vaccine GSK1024850A in study NCT00814710.

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: Pneumococcal vaccine GSK1024850A; Biological: Pneumococcal vaccine GSK1024850A

Detailed Description

The study is randomized for primed subjects and non-randomized for unprimed subjects.

The protocol posting has been updated according to the amendment of the protocol dated 16 April 2010. The age range at the time of randomization of subjects primed in study NCT00814710 and the age range for booster vaccination of one of the groups has been extended.

• Study Type: Interventional
• Enrollment (Actual): 282
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Kolkata, India, 700073
    • GSK Investigational Site
  • Ludhiana, India, 141 008
    • GSK Investigational Site
  • Pune, India
    • GSK Investigational Site
  • Vellore,, India, 632 004
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 months to 1 year (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects for whom the investigator believes that their parent(s)/ guardian(s) can and will comply with the requirements of the protocol.
• Written, signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child/ward. Where parent(s)/guardian(s) are illiterate, the consent form will be countersigned by a witness.
• Healthy subjects as established by medical history and clinical examination before entering into the study.

For primed subjects:

• Completion of the full vaccination course in study NCT00814710.
• 9-18 months of age at the time of randomization.
• Group A: 9-18 months of age at the time of booster vaccination.
• Group B: 15-18 months of age at the time of booster vaccination.

For unprimed subjects (Group C):

• Enrolled in study NCT00814710.
• 12-18 months of age at the time of first vaccination.

Exclusion Criteria:

• Use of any investigational or non-registered product within 30 days preceding the 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.
• Administration of immunoglobulins and/or any blood products within three months preceding the vaccination or planned administration during the study period.
• Administration of any pneumococcal vaccine since the end of study NCT00814710.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• History of reactions or allergic disease likely to be exacerbated by any component of the vaccine.
• Major congenital defects or serious chronic illness.
• History of any neurologic disorders or seizures.
• Acute disease at the time of enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Subjects previously primed with pneumococcal vaccine GSK1024850A in the first year of life and receiving a booster dose of GSK1024850A at 9-18 months of age.	Biological: Pneumococcal vaccine GSK1024850A; Intramuscular injection, administered as a single dose; Biological: Pneumococcal vaccine GSK1024850A; Intramuscular injection, 3 doses
Experimental: Group B; Subjects previously primed with pneumococcal vaccine GSK1024850A in the first year of life and receiving a booster dose of GSK1024850A at 15-18 months of age.	Biological: Pneumococcal vaccine GSK1024850A; Intramuscular injection, administered as a single dose; Biological: Pneumococcal vaccine GSK1024850A; Intramuscular injection, 3 doses
Experimental: Group C; Unprimed subjects receiving a catch-up vaccination (2+1 schedule) in the second year of life.	Biological: Pneumococcal vaccine GSK1024850A; Intramuscular injection, administered as a single dose; Biological: Pneumococcal vaccine GSK1024850A; Intramuscular injection, 3 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes	Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 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 enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (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.	Prior to booster vaccination (PRE), one month after booster vaccination (Month 1) and at approximately 24 months of age: at Month 15 for Synflorix 1 Group and at Month 9 for Synflorix 2 Group (24 months of age)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes	Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 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 enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (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.	Prior to vaccination (PRE), one month post-Dose 2 (Month 3), prior to (Month 6) and one month after the third (booster) vaccine dose (Month 7)
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes (Persistence)	Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 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 enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (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.	Prior to booster vaccination (PRE) for the Synflorix 1 and Synflorix 2 Groups and prior to catch-up vaccination (PRE) for the Tritanrix-HepB+Hiberix Group
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Persistence)	OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. 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.	Prior to booster vaccination (PRE) for the Synflorix 1 and Synflorix 2 Groups and prior to catch-up vaccination (PRE) for the Tritanrix-HepB + Hiberix Group
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F	OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. 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.	Prior to booster vaccination (PRE), one month after booster vaccination (Month 1) and at approximately 24 months of age: at Month 15 for the Synflorix 1 Group and at Month 9 for Synflorix 2 Group (24 months of age)
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F	OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. 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.	Prior to vaccination (PRE), one month post-Dose 2 (Month 3), prior to (Month 6) and one month after the third (booster) vaccine dose (Month 7)
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Persistence)	Antibodies assessed for this outcome measure were those against cross-reactive pneumococcal serotypes 6A and 19A (ANTI-6A and -19A). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (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.	Prior to booster vaccination (PRE) for the Synflorix 1 and Synflorix 2 Groups and prior to catch-up vaccination (PRE) for the Tritanrix-HepB + Hiberix Group
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A	Antibodies assessed for this outcome measure were those against the cross-reactive pneumococcal serotypes 6A and 19A (ANTI-6A and -19A). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (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.	Prior to booster vaccination (PRE), one month after booster vaccination (Month 1) and at approximately 24 months of age: at Month 15 for the Synflorix 1 Group and at Month 9 for the Synflorix 2 Group (24 months of age)
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A	Antibodies assessed for this outcome measure were those against cross-reactive pneumococcal serotypes 6A and 19A (ANTI-6A and -19A). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (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.	Prior to vaccination (PRE), one month post-Dose 2 (Month 3), prior to (Month 6) and one month after the third (booster) vaccine dose (Month 7)
Opsonophagocytic Activity (OPA) Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Persistence)	OPA titers against cross-reactive pneumococcal serotypes 6A and 19A (Opsono-6A and -19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. 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.	Prior to booster vaccination (PRE) for the Synflorix 1 and Synflorix 2 Groups and prior to catch-up vaccination (PRE) for the Tritanrix-HepB + Hiberix Group
Opsonophagocytic Activity (OPA) Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A	OPA titers against cross-reactive pneumococcal serotypes 6A and 19A (Opsono-6A and -19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. 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.	Prior to booster vaccination (PRE), one month after booster vaccination (Month 1) and at approximately 24 months of age: at Month 15 for the Synflorix 1 Group and at Month 9 for the Synflorix 2 Group (24 months of age)
Opsonophagocytic Activity (OPA) Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A	OPA titers against cross-reactive pneumococcal serotypes 6A and 19A (Opsono-6A and -19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. 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.	Prior to vaccination (PRE), one month post-Dose 2 (Month 3), prior to (Month 6) and one month after the third (booster) vaccine dose (Month 7)
Concentrations of Antibodies Against Protein D (Anti-PD) (Persistence)	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 milliliter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to booster vaccination (PRE) for the Synflorix 1 and Synflorix 2 Groups and prior to catch-up vaccination (PRE) for the Tritanrix-HepB + Hiberix Group
Concentrations of Antibodies Against Protein D (Anti-PD)	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 milliliter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to booster vaccination (PRE), one month after booster vaccination (Month 1) and at approximately 24 months of age: at Month 15 for the Synflorix 1 Group and at Month 9 for the Synflorix 2 Group (24 months of age)
Concentrations of Antibodies Against Protein D (Anti-PD)	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 milliliter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to vaccination (PRE), one month post-Dose 2 (Month 3), prior to (Month 6) and one month after the third (booster) vaccine dose (Month 7)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Solicited local symptoms assessed include 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.	Within the 4-day follow-up period (Days 0-3) after the booster dose for the Synflorix 1 and Synflorix 2 Groups and across doses for the Tritanrix-HepB + Hiberix Group
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were Drowsiness, Irritability/Fussiness (Irr./Fuss.), Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than [≥] 38.0 degrees Celsius [°C]),. Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal everyday activities. Grade 3 Irr./Fuss. = Crying that could not be comforted/prevented normal everyday activities. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (>) 40.0°C.	Within the 4-day follow-up period (Days 0-3) after the booster dose for the Synflorix 1 and Synflorix 2 Groups and across doses for the Tritanrix-HepB + Hiberix Group
Number of Subjects With Unsolicited Adverse Events (AEs)	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. Unsolicited AE covers any AE 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.	Within 31-day follow-up period (Days 0-30) after vaccination
Number of Subjects With Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that result in death, are life- threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity.	After the first vaccination up to study end (from Month 0 to Month 15)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Lalwani S. et al. Impact of age on booster responses to 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in children in India. Abstract presented at the 6th Asian Congress of Pediatric Infectious Diseases (ACPID), Colombo, Sri Lanka, 28 Nov - 01 Dec 2012.
• Lalwani S, Chatterjee S, Chhatwal J, Simon A, Ravula S, Francois N, Mehta S, Strezova A, Borys D. Randomized, open-label study of the impact of age on booster responses to the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in children in India. Clin Vaccine Immunol. 2014 Sep;21(9):1292-300. doi: 10.1128/CVI.00068-14. Epub 2014 Jul 9.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: April 2, 2010
• Primary Completion (Actual): August 19, 2011
• Study Completion (Actual): August 19, 2011

Study Registration Dates

• First Submitted: December 10, 2009
• First Submitted That Met QC Criteria: December 10, 2009
• First Posted (Estimate): December 14, 2009

Study Record Updates

• Last Update Posted (Actual): September 20, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Pneumococcal vaccine; Booster vaccination; Pneumococcal disease; Catch-up vaccination
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 112909

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 112909
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 112909
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 112909
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 112909
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 112909
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 112909
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: 112909
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register