Clinical trial NCT00792909: Vaccination Course in Primed Children and Age-matched Unprimed Children With Pneumococcal Vaccine GSK1024850A
Official title: Vaccination Course in Children Primed and Boosted With Pneumococcal Vaccine GSK 1024850A and in Age-matched Unprimed Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Streptococcal
Keywords: Pneumococcal vaccine
Pneumococcal disease
Safety
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-11-18
Enrollment: 172
Sex: ALL
Minimum age (years): 36
Maximum age (years): 46
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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)


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Pre-vaccination (PRE/ Day 0)
measure: 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
timeFrame: One week after dose 1 (Day 7)
measure: 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
timeFrame: One month after dose 2 (Month 3)
measure: 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
timeFrame: 1 month after booster dose (Month 10) - in primary study (105539)
measure: 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
timeFrame: Pre-additional dose at Month 34 in the current study (Month 34)
measure: 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
timeFrame: One week after vaccination at Month 34+7 days (Mth34+D7)
Secondary outcomes:
measure: 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
timeFrame: 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);
measure: 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;
timeFrame: Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3);
measure: 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
timeFrame: 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)
measure: 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
timeFrame: Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3);
measure: 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
timeFrame: 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)
measure: Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F in the Unprimed Group
timeFrame: Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
measure: Antibody Geometric Mean Concentrations (GMCs) Against the Vaccine Pneumococcal Serotypes 6A and 19A in the Synflorix™ Group 1 and Synflorix™ Group 2
timeFrame: 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)
measure: Antibody Geometric Mean Concentrations (GMCs) Against the Vaccine Pneumococcal Serotypes 6A and 19A in the Unprimed Group
timeFrame: Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
measure: Number of Subjects With Anti-pneumococcal Serotypes 6A and 19A Antibody Concentrations ≥ the Cut-off in the Synflorix™ Group 1 and Synflorix™ Group 2
timeFrame: 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)
measure: Number of Subjects With Anti-pneumococcal Serotypes 6A and 19A Antibody Concentrations ≥ the Cut-off in the Unprimed Group
timeFrame: Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
measure: Number of Subjects With Anti-pneumococcal Serotypes 6A and 19A Antibody Concentrations ≥ the Cut-off in the Synflorix™ Group 1 and Synflorix™ Group 2;
timeFrame: 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);
measure: Number of Subjects With Anti-pneumococcal Serotypes 6A and 19A Antibody Concentrations ≥ 0.20 μg/mL in the Unprimed Group
timeFrame: Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
measure: Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 6A and 19A in the Synflorix™ Group 1 and Synflorix™ Group 2
timeFrame: 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)
measure: Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 6A and 19A in the Unprimed Group
timeFrame: Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
measure: Concentrations of Antibodies Against Protein D (ANTI-PD) in the Synflorix™ Group 1 and Synflorix™ Group 2
timeFrame: 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)
measure: Concentrations of Antibodies Against Protein D (ANTI-PD) in the Unprimed Group
timeFrame: Pre-vaccination (PRE/ Day 0), one week after dose 1 (Day 7) and one month after dose 2 (Month 3)
measure: Number of Subjects With B-cells Detection in the Synflorix™ Group 1 and Synflorix™ Group 2
timeFrame: Pre-additional dose at Month 34 in the current study (Month 34) and one week after vaccination at Month 34+7 days (Mth34+D7)
measure: Number of Subjects With B-cells Detection in the Unprimed Group
timeFrame: Pre-vaccination (PRE/ Day 0) and one week after dose 1 (Day 7)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: 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
measure: Number/ Percentage of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: 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.
measure: Number (%) of Subjects With Unsolicited Adverse Events
timeFrame: 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
measure: Number (%) of Subjects With Serious Adverse Events
timeFrame: During the 31-day period following vaccination period
Other outcomes:
Locations:
city: Dlha nad Oravou
country: Slovakia
facility: GSK Investigational Site
city: Dolny Kubin
country: Slovakia
facility: GSK Investigational Site
city: Ruzomberok
country: Slovakia
facility: GSK Investigational Site
city: Umeå
country: Sweden
facility: GSK Investigational Site
city: Örebro
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Silfverdal SA, Skerlikova H, Zanova M, Papuchova 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.
citation: 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.
citation: 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.