Clinical trial NCT00652951: Co-administration of Pneumococcal Conjugate Vaccine With DTPa-IPV-Hib Versus Co-administration With DTPa-HBV-IPV/Hib
Official title: Non-inferiority of Co-administration of GSK Biologicals'Pneumococcal Conjugate Vaccine GSK1024850A With DTPa-IPV-Hib Versus Co-administration With DTPa-HBV-IPV/Hib.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Streptococcal
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-04-04
Enrollment: 780
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this trial is to evaluate the immunogenicity and safety of a pneumococcal conjugate vaccine when co-administered with DTPa-IPV-Hib or DTPa-HBV-IPV/Hib in infants as a three-dose primary immunisation course during the first 6 months of life and as a booster dose at 11-12 months of age. The impact of the pneumococcal conjugate vaccine on nasopharyngeal carriage of S. pneumoniae and H. influenzae in children in their first two years of life will also be assessed. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.


Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that their parents/guardian(s) can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study.
* A male or female between, and including, 6-12 weeks (42-90 days) of age at the time of the first vaccination.
* Written informed consent obtained from both parents or from the guardian(s) 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 of at least 36 weeks.

Exclusion Criteria:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Concurrently participating in another clinical study, at any time during the entire study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
* Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from one month (30 days) before and up to one month (30 days) after each dose of study vaccine.
* Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae.
* Children for whom hepatitis B vaccination is required according to the local recommendations
* History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, Haemophilus influenzae type b disease.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
* History of any neurologic disorders or seizures.
* 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 study period.

Primary outcomes:
measure: Antibody Concentrations Against 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) - Primary Vaccination
timeFrame: At Month 3, one month after the administration of the third dose of pneumococcal conjugate vaccine
measure: Antibody Concentration Against Protein D (PD) - Primary Vaccination
timeFrame: At Month 3, one month after the administration of the third dose of pneumococcal conjugate vaccine
Secondary outcomes:
measure: Number of Subjects With Antibody Concentrations Against 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) ≥ 0.2 μg/mL - Primary Vaccination
timeFrame: At Month 3, one month after the administration of the third vaccine dose
measure: Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Primary Vaccination
timeFrame: At Month 3, one month after the administration of the third vaccine dose
measure: Number of Subjects With Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Primary Vaccination.
timeFrame: At Month 3, one month after the administration of the third vaccine dose
measure: Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) - Primary Vaccination
timeFrame: At Month 3, one month after the administration of the third vaccine dose
measure: Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A - Primary Vaccination.
timeFrame: At Month 3, one month after the administration of the third vaccine dose
measure: Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T) - Primary Vaccination
timeFrame: At Month 3, one month after the administration of the third vaccine dose
measure: Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations - Primary Vaccination
timeFrame: At Month 3, one month after the administration of the third vaccine dose
measure: Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations - Primary Vaccination
timeFrame: At Month 3, one month after the administration of the third vaccine dose
measure: Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations - Primary Vaccination.
timeFrame: At Month 3, one month after the administration of the third vaccine dose
measure: Anti-polio Types 1, 2 and 3 Titers - Primary Vaccination.
timeFrame: At Month 3, one month after the administration of the third vaccine dose
measure: Number of Subjects With Antibody Concentrations Against 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) ≥ 0.2 μg/mL - Booster Vaccination
timeFrame: Prior to (Month 9) and one month after the administration of the booster dose (Month 10)
measure: Antibody Concentrations Against 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) - Booster Vaccination
timeFrame: Prior (Month 9) to and one month after the administration of the booster dose (Month 10)
measure: Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Booster Vaccination
timeFrame: Prior (Month 9) to and one month after the administration of the booster dose(Month 10)
measure: Number of Subjects With Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Booster Vaccination.
timeFrame: Prior (Month 9) to and one month after the administration of the booster dose(Month 10)
measure: Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) - Booster Vaccination
timeFrame: Prior (Month 9) to and one month after the administration of the booster dose (Month 10)
measure: Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A - Booster Vaccination.
timeFrame: Prior to (Month 9) and one month after the administration of the booster dose (Month 10)
measure: Concentrations of Antibodies Against Protein D (Anti-PD) - Booster Vaccination.
timeFrame: Prior (Month 9) to and one month after (Month 10) the administration of the booster dose
measure: Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T) - Booster Vaccination.
timeFrame: Prior to (Month 9) and one month after (Month 10) the administration of the booster dose
measure: Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations - Booster Vaccination
timeFrame: Prior to (Month 9) and one month after (Month 10) the administration of the booster dose
measure: Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations - Booster Vaccination.
timeFrame: Prior (Month 9) to and one month after (Month 10) the administration of the booster dose
measure: Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations - Booster Vaccination.
timeFrame: Prior (Month 9) to and one month after (Month 10) the administration of the booster dose
measure: Anti-polio Types 1, 2 and 3 Titers - Booster Vaccination.
timeFrame: Prior (Month 9) to and one month after (Month 10) the administration of the booster dose
measure: Number of Subjects With Booster Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antibodies - Booster Vaccination.
timeFrame: One month after (Month 10) the administration of the booster dose
measure: Number of Subjects With Antibody Concentrations Against 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) ≥ 0.2 μg/mL - 12 Months After Booster Dose.
timeFrame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
measure: Antibody Concentrations Against 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) - 12 Months After Booster Dose.
timeFrame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
measure: Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - 12 Months After Booster Dose.
timeFrame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
measure: Number of Subjects With Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - 12 Months After Booster Dose.
timeFrame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
measure: Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) - 12 Months After Booster Dose.
timeFrame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
measure: Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A - 12 Months After Booster Dose.
timeFrame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
measure: Concentrations of Antibodies Against Protein D (Anti-PD) - 12 Months After Booster Dose.
timeFrame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
measure: Number of Subjects With Positive Cultures of Haemophilus Influenzae and/or Streptococcus Pneumoniae in the Nasopharynx - Primary Vaccination.
timeFrame: One month after the third dose (Month 3), prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)
measure: Number of Subjects With Positive Cultures of Streptococcus Pneumoniae Vaccine Seroptypes (VS), Cross-reactive Serotypes (CRS) or Other Serotypes (OS) in the Nasopharynx - Primary Vaccination.
timeFrame: One month after the third dose (Month 3), prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)
measure: Number of Subjects With Acquisition of New Streptococcus Pneumoniae and Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs - Primary Vaccination.
timeFrame: Prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)
measure: Number of Subjects With Acquisition of New Streptococcus Pneumoniae Vaccine Serotypes (VS), Cross-reactive Serotypes (CRS) or Other Serotypes (OS) Identified in Nasopharyngeal Swabs - Primary Vaccination.
timeFrame: Prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)
measure: Number of Subjects With Solicited Local Symptoms - Primary Vaccination
timeFrame: During the 4-day (Days 0-3) post-vaccination period following each dose and across doses
measure: Number of Subjects With Solicited General Symptoms - Primary Vaccination
timeFrame: During the 4-day (Days 0-3) post-vaccination period following each dose and across doses
measure: Number of Subjects With Unsolicited Adverse Events (AEs) - Primary Vaccination.
timeFrame: Within the 31-day (Days 0-30) post-primary vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Throughout the entire study period (up to Month 21)
measure: Number of Subjects With Solicited Local Symptoms -Booster Vaccination
timeFrame: During the 4-day (Days 0-3) post-vaccination period following booster dose
measure: Number of Subjects With Solicited General Symptoms - Booster Vaccination.
timeFrame: During the 4-day (Days 0-3) post-vaccination period following booster dose
measure: Number of Subjects With Unsolicited Adverse Events (AEs) - Booster Vaccination.
timeFrame: Within the 31-day (Days 0-30) after booster vaccination
Other outcomes:
Locations:
city: Hoofddorp
country: Netherlands
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: van den Bergh MR, Spijkerman J, Francois N, Swinnen K, Borys D, Schuerman L, Veenhoven RH, Sanders EA. Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine and DTPa-IPV-Hib when coadministered as a 3-dose primary vaccination schedule in The Netherlands: a randomized controlled trial. Pediatr Infect Dis J. 2011 Sep;30(9):e170-8. doi: 10.1097/INF.0b013e31821a0614.
citation: van den Bergh MR, Spijkerman J, Swinnen KM, Francois NA, Pascal TG, Borys D, Schuerman L, Ijzerman EP, Bruin JP, van der Ende A, Veenhoven RH, Sanders EA. Effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine on nasopharyngeal bacterial colonization in young children: a randomized controlled trial. Clin Infect Dis. 2013 Feb;56(3):e30-9. doi: 10.1093/cid/cis922. Epub 2012 Nov 1.
citation: van den Bergh MR, Spijkerman J, Francois N, Swinnen K, Borys D, Schuerman L, Veenhoven RH, Sanders EA. Immunogenicity, Safety and Reactogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable H. influenzae Protein D Conjugate Vaccine Coadministered With DTPa-IPV-Hib in Dutch Children: A Randomized Controlled Trial. Pediatr Infect Dis J. 2016 Jul;35(7):e206-19. doi: 10.1097/INF.0000000000001170.