Clinical trial NCT00345358: Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' 10-valent Pneumococcal Conjugate Vaccine
Official title: Evaluate Immunogenicity, Safety & Reactogenicity of GSK Biologicals' 10-valent Pneumococcal Conjugate Vaccine Given as Catch-up Immunization in Children Older Than 7 mo of Age or as 3-dose Primary Immunization in Children Before 6 mo of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Streptococcal
Keywords: Booster vaccination
Catch-up vaccination
Pneumococcal vaccine
Immunogenicity
Safety
Pneumococcal disease
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-06-28
Enrollment: 600
Sex: ALL
Minimum age (years): 9
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this phase IIIb study is to determine whether children who have not received a 3-dose primary vaccination with the pneumococcal conjugate vaccine before their 6 months of age, can receive the vaccine as part of a catch-up immunization schedule. The immunogenicity, safety and reactogenicity of GSK Biologicals' pneumococcal conjugate vaccine will be evaluated for four different age groups with different schedules:

\< 6 months of age group: 3-dose primary vaccination + a booster dose. 7 to 11 months of age group: 2-dose primary vaccination + a booster dose. 12 to 23 months of age group: 2-dose vaccination; no booster dose. 24 months to 5 years of age group: 1-dose vaccination; no booster dose. Children below 6 months of age will receive concomitantly a DTPa-IPV/Hib vaccine.

Detailed description: The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007

Eligibility criteria: Inclusion Criteria:

* Male or female between, and including

  * 9-12 weeks of age at the time of first vaccination for the \<6 Mo group.
  * 7-11 months of age at the time of first vaccination for the 7-11 Mo group.
  * 12-23 months of age at the time of first vaccination for the 12-23 Mo group.
  * 24 months to 5 years at the time of first vaccination for the \>= 24 Mo group.
* Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol
* Written informed consent obtained from the parent or guardian of the subject.
* Free of obvious health problems as established by medical history and clinical examination before entering into the study.
* Born after a gestation period between 36 and 42 weeks.

Exclusion Criteria:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the entire study period for each age-group.
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
* Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting one month before and ending one month after each dose of vaccine(s).
* Previous vaccination against S. pneumoniae.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
* History of seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past) or neurological disease.
* Acute disease at the time of enrolment.
* Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination
* A family history of congenital or hereditary immunodeficiency.
* Major congenital defects or serious chronic illness.
* Administration of immunoglobulins and/or any blood products since birth or planned administration during the entire study period.

Primary outcomes:
measure: Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations >= 0.20 Microgram Per Milliliter (µg/mL). (Primary/Full Vaccination)
timeFrame: At one month after primary (Synflorix <6M & Synflorix 7-11M Groups) or after the full (Synflorix 12-23M & Synflorix >=24M Groups) vaccination course with Synflorix™, that is Month (M)3 for Synflorix <6M & 12-23M groups, M2 for Synflorix 7-11M Group, & M1
Secondary outcomes:
measure: Antibody Concentrations Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. (Primary/Full Vaccination)
timeFrame: At 1 month after the administration of the primary (< 6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with Synflorix™ vaccine.
measure: Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A. (Primary/Full Vaccination)
timeFrame: At 1 month after the administration of the primary (< 6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with Synflorix™ vaccine.
measure: Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. (Primary/Full Vaccination)
timeFrame: At 1 month after the administration of the primary (< 6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with Synflorix™ vaccine.
measure: Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A. (Primary/Full Vaccination)
timeFrame: At 1 month after the administration of the primary (< 6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with Synflorix™ vaccine.
measure: Antibody Concentrations Against Protein D (Anti-PD). (Primary/Full Vaccination)
timeFrame: At 1 month after the administration of the primary (< 6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with Synflorix™ vaccine.
measure: Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations >= 0.20 µg/mL. (Booster Vaccination)
timeFrame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups
measure: Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations. (Booster Vaccination)
timeFrame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups
measure: Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A.(Booster Vaccination)
timeFrame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups
measure: Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. (Booster Vaccination)
timeFrame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups
measure: Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A. (Booster Vaccination)
timeFrame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups
measure: Antibody Concentrations Against Protein D. (Booster Vaccination)
timeFrame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups
measure: Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-T) Antibody Concentrations. (Primary Vaccination)
timeFrame: At 1 month after the administration of the primary vaccination course (Month [M]3 = POST-PRY) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.
measure: Anti-polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations. (Primary Vaccination)
timeFrame: At 1 month after the administration of the primary vaccination course (Month [M]3 = POST-PRY) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group
measure: Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibody Concentrations. (Primary Vaccination)
timeFrame: At 1 month after the administration of the primary vaccination course(Month [M]3 = POST-PRY) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group
measure: Anti-polio Type 1, 2 and 3 Titers. (Primary Vaccination)
timeFrame: At 1 month after the administration of the primary vaccination course (Month [M]3 = POST-PRY) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.
measure: Booster Vaccine Response to PT, FHA and PRN
timeFrame: Before and one month after the booster dose with Synflorix™
measure: Number of Subjects Solicited Local Symptoms (Any and Grade 3). (Primary Vaccination)
timeFrame: Within 4-day (Days 0-3) following the primary vaccination
measure: Number of Subjects With Solicited Local Symptoms (Any and Grade 3). (Booster Vaccination)
timeFrame: Within 4-day (Days 0-3) following the booster vaccination
measure: Number of Subjects With Solicited General Symptoms (Any and Grade 3). (Booster Vaccination)
timeFrame: Within 4 day (Days 0-3) following the booster vacination
measure: Number of Subjects With Unsolicited Adverse Events (AEs). (Primary Vaccination)
timeFrame: Within 31-day (Days 0-30) post primary vaccination
measure: Number of Subjects With Unsolicited Adverse Events (AEs). (Booster Vaccination)
timeFrame: Within 31 day (Days 0-30) following the booster vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs) (Primary Vaccination)
timeFrame: During the Primary vaccination course up until start of Booster vaccination course
measure: Number of Subjects With Serious Adverse Events (SAEs). (Booster Vaccination)
timeFrame: During the booster vaccination course
measure: Number of Subjects With Solicited General Symptoms (Primary Vaccination)
timeFrame: Within 4-day (Days 0-3) following the primary vaccination
measure: Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-T) Antibody Concentrations.(Booster Vaccination)
timeFrame: Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.
measure: Anti-polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations. (Booster Vaccination)
timeFrame: Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.
measure: Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibody Concentrations. (Booster Vaccination)
timeFrame: Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.
measure: Titers of Antibodies Against Polio Type 1, 2 and 3 (Anti-polio 1, 2 and 3). (Booster Vaccination)
timeFrame: Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.
Other outcomes:
Locations:
city: Espoo
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Jarvenpaa
country: Finland
facility: GSK Investigational Site
city: Kotka
country: Finland
facility: GSK Investigational Site
city: Lahti
country: Finland
facility: GSK Investigational Site
city: Seinajoki
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Vantaa
country: Finland
facility: GSK Investigational Site
city: Vantaa
country: Finland
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Vesikari T, Karvonen A, Korhonen T, Karppa T, Sadeharju K, Fanic A, Dieussaert I, Schuerman L. Immunogenicity of 10-valent pneumococcal nontypeable Haemophilus Influenzae Protein D Conjugate Vaccine when administered as catch-up vaccination to children 7 months to 5 years of age. Pediatr Infect Dis J. 2011 Aug;30(8):e130-41. doi: 10.1097/INF.0b013e31821d1790.