Vaccination Course in Primed Children and Age-matched Unprimed Children With Pneumococcal Vaccine GSK1024850A

Infections, Streptococcal Clinical Trial

Official title:

Vaccination Course in Children Primed and Boosted With Pneumococcal Vaccine GSK 1024850A and in Age-matched Unprimed Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00792909
• Other study ID #: 111736
• Status: Completed
• Phase: Phase 3
• First received: November 17, 2008
• Last updated: May 12, 2017
• Start date: December 2, 2008
• Est. completion date: July 2, 2009

Study information

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

Clinical Trial Summary

The purpose of this study is to assess the immune memory induced by primary and booster vaccination with pneumococcal conjugate vaccine GSK1024850A in the first year of life through evaluation of the immune responses following vaccination with a booster dose of pneumococcal conjugate vaccine GSK1024850A in the fourth year of life and to assess immune responses following vaccination with a single dose of pneumococcal conjugate vaccine GSK1024850A in age-matched unprimed children.

The study also aims to assess the antibody persistence in the fourth year of life following primary and booster vaccination with pneumococcal conjugate vaccine GSK1024850A in the first year of life.

The study is also designed to evaluate the immunogenicity in terms of antibody response and the safety/reactogenicity in terms of solicited and unsolicited symptoms and serious adverse events following a 2-dose vaccination with pneumococcal conjugate vaccine GSK1024850A in the fourth year of life.

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 = 00307034)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 172
• Est. completion date: July 2, 2009
• Est. primary completion date: July 2, 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 36 Months to 46 Months

Eligibility

Inclusion Criteria:

• Male or female between, and including, +- 36-46 months of age at the time of vaccination.

• For primed subjects: having completed the full vaccination course with GSK1024850A in the primary study (NCT00307034).

• Subjects for whom the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol.

• Written informed consent obtained from the parent(s)/guardian(s) of the subject.

• Free of obvious health problems as established by medical history and clinical examination before entering into the study

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, or planned use during the study period.

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to vaccination.

• For primed subjects: administration of any pneumococcal vaccine since the end of the primary study (NCT00307034).

• For unprimed subjects: previous vaccination with any pneumococcal vaccine.

• Administration of immunoglobulins and/or any blood products less than 6 months prior to the vaccination or planned administration during the study period.

• 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 study vaccine.

• Acute disease at the time of enrolment.

Related Conditions & MeSH terms

• Infections, Streptococcal
• Streptococcal Infections

Intervention

Biological:
• Pneumococcal conjugate vaccine GSK1024850A
Intramuscular injection, 1 dose
• Pneumococcal conjugate vaccine GSK1024850A
Intramuscular injection, 2 doses

Locations

Country	Name	City	State
Slovakia	GSK Investigational Site	Dlha nad Oravou
Slovakia	GSK Investigational Site	Dolny Kubin
Slovakia	GSK Investigational Site	Ruzomberok
Sweden	GSK Investigational Site	Örebro
Sweden	GSK Investigational Site	Umeå

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Slovakia,  Sweden, 

References & Publications (3)

Silfverdal SA et al. Assessment of immunological memory following PHiD-CV immunisation according to 2+1 or 3+1 schedules in the first year of life. Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.

Silfverdal SA et al. Immunogenicity/reactogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) during fourth year of life. Abstract presented at the 8th Biennial International Symposium on Pneumococci & Pneumococcal Diseases (ISPPD), Foz de Iguaçu, Brazil, 11-15 March 2012.

Silfverdal SA, Skerlikova H, Zanova M, Papúchová D, Traskine M, Borys D, Schuerman L. Anamnestic immune response in 3- to 4-year-old children previously immunized with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine as 2-dose or 3-dose priming and a booster dose in the first year of life. Pediatr Infect Dis J. 2011 Sep;30(9):e155-63. doi: 10.1097/INF.0b013e31821feeb7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody Geometric Mean Concentrations (GMCs) Against the Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F in the Unprimed Group	Antibodies assessed 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) and 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 greater than or equal to (=) 0.05 µg/mL.	Pre-vaccination (PRE/ Day 0)
Primary	Antibody Geometric Mean Concentrations (GMCs) Against the Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F in the Unprimed Group	Antibodies assessed 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) and 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.	One week after dose 1 (Day 7)
Primary	Antibody Geometric Mean Concentrations (GMCs) Against the Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F in the Unprimed Group	Antibodies assessed 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) and 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.	One month after dose 2 (Month 3)
Primary	Antibody Geometric Mean Concentrations (GMCs) Against the Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F in the Synflorix Group 1 and Synflorix Group 2	Antibodies assessed 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) and 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.	1 month after booster dose (Month 10) - in primary study (105539)
Primary	Antibody Geometric Mean Concentrations (GMCs) Against the Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F in the Synflorix Group 1 and Synflorix Group 2	Antibodies assessed 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) and 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.	Pre-additional dose at Month 34 in the current study (Month 34)
Primary	Antibody Geometric Mean Concentrations (GMCs) Against the Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F in the Synflorix Group 1 and Synflorix Group 2	Antibodies assessed 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) and 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.	One week after vaccination at Month 34+7 days (Mth34+D7)
Secondary	Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations = the Cut-off in the Synflorix™ Group 1 and Synflorix™ Group 2	Antibodies assessed 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) and 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..	1 month after booster dose (Month 10) - in primary study (105539), pre-additional dose at Month 34 in the current study (Month 34) and one week after vaccination at Month 34+7 days (Mth34+ D7);
Secondary	Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations = the Cut-off in the Unprimed Group;	Antibodies assessed 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) and 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.	Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3);
Secondary	Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations = the Cut-off in the Synflorix™ Group 1 and Synflorix™ Group 2	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 = 0.2 µg/mL.	1 month after booster dose (Month 10) - in primary study (105539), pre-additional dose at Month 34 in the current study (Month 34) and one week after vaccination at Month 34+7 days (Mth34+D7)
Secondary	Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations = the Cut-off in the Unprimed Group	Antibodies assessed 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) and 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 = 0.20 µg/mL.	Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3);
Secondary	Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F in the Synflorix™ Group 1 and Synflorix™ Group 2	Seropositivity status was defined as opsonophacocytic activity against pneumococcal serotypes = 8.	1 month after booster dose (Month 10) - in primary study (105539), pre-additional dose at Month 34 in the current study (Month 34) and one week after vaccination at Month 34+7 days (Mth34+D7)
Secondary	Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F in the Unprimed Group	Seropositivity status was defined as opsonophacocytic activity against pneumococcal serotypes = 8.	Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
Secondary	Antibody Geometric Mean Concentrations (GMCs) Against the Vaccine Pneumococcal Serotypes 6A and 19A in the Synflorix™ Group 1 and Synflorix™ Group 2	Antibodies assessed were those against the vaccine pneumococcal serotypes 6A and19A (ANTI-6A and19A) and 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.	1 month after booster dose (Month 10) - in primary study (105539), pre-additional dose at Month 34 in the current study (Month 34) and one week after vaccination at Month 34+7 days (Mth34+D7)
Secondary	Antibody Geometric Mean Concentrations (GMCs) Against the Vaccine Pneumococcal Serotypes 6A and 19A in the Unprimed Group	Antibodies assessed were those against the vaccine pneumococcal serotypes 6A and 19A (ANTI-6A and 19A) and 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.	Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
Secondary	Number of Subjects With Anti-pneumococcal Serotypes 6A and 19A Antibody Concentrations = the Cut-off in the Synflorix™ Group 1 and Synflorix™ Group 2	Antibodies assessed were those against the vaccine pneumococcal serotypes 6A and 19A (ANTI-6A and 19A) and 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.	1 month after booster dose (Month 10) - in primary study (105539), pre-additional dose at Month 34 in the current study (Month 34) and one week after vaccination at Month 34+7 days (Mth34+D7)
Secondary	Number of Subjects With Anti-pneumococcal Serotypes 6A and 19A Antibody Concentrations = the Cut-off in the Unprimed Group	Antibodies assessed were those against the vaccine pneumococcal serotypes 6A and 19A (ANTI-6A and 19A) and 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.	Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
Secondary	Number of Subjects With Anti-pneumococcal Serotypes 6A and 19A Antibody Concentrations = the Cut-off in the Synflorix™ Group 1 and Synflorix™ Group 2;	Antibodies assessed were those against the vaccine pneumococcal serotypes 6A and 19A (ANTI-6A and 19A) and 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 = 0.20 µg/mL.	1 month after booster dose (Month 10) - in primary study (105539), pre-additional dose at Month 34 in the current study (Month 34) and one week after vaccination at Month 34+7 days (Mth34+D7);
Secondary	Number of Subjects With Anti-pneumococcal Serotypes 6A and 19A Antibody Concentrations = 0.20 µg/mL in the Unprimed Group	Antibodies assessed were those against the vaccine pneumococcal serotypes 6A and 19A (ANTI-6A and 19A) and 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 = 0.20 µg/mL.	Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
Secondary	Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 6A and 19A in the Synflorix™ Group 1 and Synflorix™ Group 2	Seropositivity status defined as opsonophacocytic activity against pneumococcal serotypes = 8	1 month after booster dose (Month 10) - in primary study (105539), pre-additional dose at Month 34 in the current study (Month 34) and one week after vaccination at Month 34+7 days (Mth34+D7)
Secondary	Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 6A and 19A in the Unprimed Group	Seropositivity status defined as opsonophacocytic activity against pneumococcal serotypes = 8.	Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
Secondary	Concentrations of Antibodies Against Protein D (ANTI-PD) in the Synflorix™ Group 1 and Synflorix™ Group 2	ANTI-PD concentrations were expressed as geometric mean concentrations (GMCs), in enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL). Seropositivity status was defined as Anti-PD antibody concentrations = 100 EL.U/mL.	1 month after booster dose (Month 10) - in primary study (105539), pre-additional dose at Month 34 in the current study (Month 34) and one week after vaccination at Month 34+7 days (Mth34+D7)
Secondary	Concentrations of Antibodies Against Protein D (ANTI-PD) in the Unprimed Group	ANTI-PD concentrations were expressed as geometric mean concentrations (GMCs), in enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL). Seropositivity status was defined as Anti-PD antibody concentrations = 100 EL.U/mL.	Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
Secondary	Number of Subjects With B-cells Detection in the Synflorix™ Group 1 and Synflorix™ Group 2	Quantification of memory B-cells that produce antibodies against vaccine pneumococcal serotypes (PS) 6B, 18C, 19F, 23F and C-PS (Elispot assay), prior to and 7-10 days post- additional dose.	Pre-additional dose at Month 34 in the current study (Month 34) and one week after vaccination at Month 34+7 days (Mth34+D7)
Secondary	Number of Subjects With B-cells Detection in the Unprimed Group	Quantification of memory B-cells that produce antibodies against vaccine pneumococcal serotypes (PS) 6B, 18C, 19F, 23F and C-PS (Elispot assay), prior to, and 7-10 days post-dose 1.	Pre-vaccination (PRE/ Day 0) and one week after dose 1 (Day 7)
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Assessed local symptoms were pain, redness and swelling. Any = occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = crying when limb was moved/ spontaneously painful. Grade 3 Redness/ Swelling = Redness/ swelling at injection site greater than (>) 30 millimeters (mm).	During the 4-day (Days 0-3) post-vaccination period with the Synflorix™ vaccine, following the additional dose in the Synflorix Group1 and the Synflorix Group2 and across the 2 doses in the Unprimed Group
Secondary	Number/ Percentage 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 = 38.0 °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 = not eating at all. Grade 3 fever = rectal temperature > 40.0°C.	During the 4-day (Days 0-3) post-vaccination period with the Synflorix™ vaccine, following the additional dose in the Synflorix Group 1 and the Synflorix Group 2 and across the 2 doses in the Unprimed Group.
Secondary	Number (%) of Subjects With Unsolicited Adverse Events	An unsolicited AE was defined as 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 = occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.	Within the 31-day (Days 0-30) period post vaccination, with the Synflorix™ vaccine, following the additional dose in the Synflorix group1 and the Synflorix Group 2 and across the 2 doses in the Unprimed Group
Secondary	Number (%) of Subjects With Serious Adverse Events	A serious adverse event (SAE) was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalisation, as per the medical or scientific judgement of the physician. Any = occurrence of a SAE, regardless of relationship to vaccination.	During the 31-day period following vaccination period

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