Booster and Catch-up Vaccination With Vaccine GSK1024850A

Infections, Streptococcal Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01030822
• Other study ID #: 112909
• Status: Completed
• Phase: Phase 3
• Start date: April 2, 2010
• Est. completion date: August 19, 2011

Study information

• Verified date: January 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: August 19, 2011
• Est. primary completion date: August 19, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 9 Months to 18 Months

Eligibility

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.

Related Conditions & MeSH terms

• Infections, Streptococcal
• Streptococcal Infections

Intervention

Biological:
• Pneumococcal vaccine GSK1024850A
Intramuscular injection, administered as a single dose
• Pneumococcal vaccine GSK1024850A
Intramuscular injection, 3 doses

Locations

Country	Name	City	State
India	GSK Investigational Site	Kolkata
India	GSK Investigational Site	Ludhiana
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Vellore,

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

India, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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)

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