Safety & Immunogenicity Study of 10-Valent Pneumococcal Conjugate Vaccine When Administered as a 2-Dose Schedule

An Open, Randomized, Phase IIIa Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' 10-valent Pneumococcal Conjugate Vaccine, When Administered Intramuscularly According to a 2-4-11 Months Vaccination Schedule

Assess immuno, reacto of the 10-valent pneumococcal vaccine after 2 doses (2, 4 months of age) and after the complete 2, 4, 11 months schedule when co-administered with DTPa-HBV-IPV/Hib or DTPa-IPV/Hib (according to national recommendations)

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: GSK Biologicals' 10-valent pneumococcal conjugate vaccine.; Biological: Infanrix hexa.; Biological: Infanrix-IPV/Hib.

Detailed Description

Total anticipated: 300 subjects (150/group). 2-dose group - 10-valent pneumococcal vaccine + DTPa combined vaccine (2, 4, 11 months); Comparator group - 10-valent pneumococcal vaccine (2, 3, 4, 11 months) + DTPa combined vaccine (2, 4, 11 months). The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

• Study Type: Interventional
• Enrollment (Actual): 351
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • GSK Investigational Site
• Norway
  • Morvik, Norway, 5125
    • GSK Investigational Site
  • Oslo, Norway, 0130
    • GSK Investigational Site
• Slovakia
  • Dolny Kubin, Slovakia, 026 01
    • GSK Investigational Site
  • Ruzomberok, Slovakia, 034 01
    • GSK Investigational Site
• Sweden
  • Göteborg, Sweden, SE-416 73
    • GSK Investigational Site
  • Umeå, Sweden, SE-901 85
    • GSK Investigational Site
  • Örebro, Sweden, SE-702 11
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 3 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
• A male or female between, and including, 8 and 16 weeks (56-120 days) of age at the time of the first vaccination.
• 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 of 36 to 42 weeks.

Exclusion criteria:

• Use of any investigational or non-registered 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.
• Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days before the first dose of vaccine(s) and ending 30 days after the last dose, with exception of BCG vaccination which can be given after the 1 month post-dose 2 or 3 (2-4-11 or 2-3-4-11 months of age schedule) blood sampling and a minimum of 30 days before the pre-booster dose blood sampling.
• Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, and/or S. pneumoniae.
• History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, Haemophilus influenzae type b disease, and/or invasive pneumococcal diseases.
• 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.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2-dose group; Subjects receiving GSK Biologicals' 10-valent pneumococcal conjugate vaccine at 2-4-11 months of age, co-administered with DTPa-combined vaccine (Infanrix hexa or Infanrix IPV/Hib) at 2-4-11 months of age.	Biological: GSK Biologicals' 10-valent pneumococcal conjugate vaccine.; Intramuscular injection, 3 or 4 doses (2-4-11 or 2-3-4-11 months of age schedule).; Biological: Infanrix hexa.; Intramuscular injection, 3 doses (2-4-11 months of age schedule).; Other Names: DTPa-HBV-IPV/Hib; Biological: Infanrix-IPV/Hib.; Intramuscular injection, 3 doses (2-4-11 months of age schedule).; Other Names: DTPa-IPV/Hib
Experimental: Comparator group; Subjects receiving GSK Biologicals' 10-valent pneumococcal conjugate vaccine at 2-3-4-11 months of age, co-administered with DTPa-combined vaccine (Infanrix hexa or Infanrix IPV/Hib) at 2-4-11 months of age.	Biological: GSK Biologicals' 10-valent pneumococcal conjugate vaccine.; Intramuscular injection, 3 or 4 doses (2-4-11 or 2-3-4-11 months of age schedule).; Biological: Infanrix hexa.; Intramuscular injection, 3 doses (2-4-11 months of age schedule).; Other Names: DTPa-HBV-IPV/Hib; Biological: Infanrix-IPV/Hib.; Intramuscular injection, 3 doses (2-4-11 months of age schedule).; Other Names: DTPa-IPV/Hib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroprotected Subjects Against Pneumococcal Serotypes	A seroprotected subject was defined as a subject who had anti-pneumococcal serotypes antibody concentrations greater than or equal to (≥) the threshold value of 0.20 micrograms per milliliter (μg/mL). The vaccine pneumococcal serotypes assessed were 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). The results presented for the Group 1 correspond to the primary outcome.	One month post-dose 2 (Month 3) administration of Synflorix™ vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroprotected Subjects Against Pneumococcal Serotypes	A seroprotected subject was defined as a subject who had anti-pneumococcal serotypes antibody concentrations greater than or equal to (≥) the threshold value of 0.20 micrograms per milliliter (μg/mL). The vaccine pneumococcal serotypes assessed were 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).	One month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine
Antibody Concentrations Against Pneumococcal Serotypes	The vaccine pneumococcal serotypes assessed were 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. This outcome concerns results for the Primary and Booster Phases of the study.	One month post-dose 2 or post-dose 3 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes	Seropositivity status was defined as the opsonophacocytic activity against pneumococcal serotypes greater than or egual to (≥) the value of 8. The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C,19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F).This outcome concerns results for the Primary and Booster Phases of the study.	One month post-dose 2 or post-dose 3 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine
Antibody Concentrations Against Protein D (Anti-PD)	Anti-protein D concentrations are expressed as geometric mean concentrations (GMCs), in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).Seropositivity status was defined as Anti-PD antibody concentrations greater than or equal to (≥) the value of 100 EL.U/mL. This outcome concerns results for the Primary and Booster Phases of the study.	One month post-dose 2 or post-dose 3 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine
Antibody Concentrations Against Diphteria (Anti-D) and Tetanus (Anti-T) Toxoids	Concentrations of antibodies are presented as geometric mean concentrations, expressed as international units per milliliter (IU/mL). Seroprotection status was defined as anti-diphteria and anti-tetanus toxoid antibody concentrations greater than or equal to (≥) the value of 0.1 IU/mL. This outcome concerns results for the Primary and Booster Phases of the study.	One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine
Antibody Concentrations Against Polyribosyl Ribitol Phosphate (Anti-PRP)	Concentrations of antibodies are presented as geometric mean concentrations, expressed as micrograms per milliliter (μg/mL). Seroprotection status was defined as anti-polyribosyl ribitol phosphate (Anti-PRP) antibody concentrations greater than or equal to (≥) the cut-off values of 0.15 μg/mL and ≥ 1.0 μg/mL. This outcome concerns results for the Primary and Booster Phases of the study.	One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) booster dose of Synflorix™ vaccine
Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA) and Pertactin (Anti-PRN)	Concentrations of antibodies are presented as geometric mean concentrations, expressed as enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). Seropositivity status was defined as anti-pertussis toxoid (Anti-PT), anti-filamentous haemagglutinin (Anti-FHA) and anti-pertactin (Anti-PRN) antibody concentrations greater than or equal to (≥) the cut-off value of 5 EL.U/mL. This outcome concerns results for the Primary and Booster Phases of the study.	One month post-dose 2 (Month 3) administration, one month before (Month 9) and after (Month 10) the booster dose of Synflorix™ vaccine
Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs)	Concentrations of antibodies are presented as geometric mean concentrations, expressed as milli international units per milliliter (mIU/mL). Seroprotection status was defined as anti-hepatitis B surface antigen (anti-HBs) antibody concentrations greater than or equal to (≥) the cut-off value of 10 mIU/mL. This outcome concerns results for the Primary and Booster Phases of the study and included only the subset of subjects who received Infanrix Hexa™ as the co-administered vaccine.	One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine
Antibody Titers Against Polio Type 1, 2 and 3 (Anti-polio 1, 2 and 3)	Titers of antibodies are presented as geometric mean titers. Seroprotection status was defined as anti-polio types 1, 2 and 3 (Anti-polio 1, 2 and 3) antibody titers greater than or equal to (≥) the value of 8. This outcome concerns results for the Primary and Booster Phases of the study and included only the subset of subjects who received Infanrix Hexa™ as the co-administered vaccine.	One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine
Number of Subjects With Booster Vaccine Response to Anti-PT, Anti-FHA and Anti-PRN Antibodies	Booster vaccine response to pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN), defined as the appearance of antibodies in subjects who were seronegative (Pre-booster status S-) (i.e., with antibody concentrations < 5 EL.U/mL) just before booster dose, and at least two-fold increase of pre-vaccination antibody concentrations in those who were seropositive (Pre-booster status S+) (i.e., with antibody concentrations ≥ 5 EL.U/mL) just before booster dose.	One month after (Month 9) the administration of the booster dose of Synflorix™ vaccine
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 larger than (>) 30 millimeters (mm). Across doses= across the 2 doses of the Synflorix™ vaccine in the Synflorix I group and across the 3 doses of the Synflorix™ vaccine in the Synflorix II group.	During the 4-day (Days 0-3) period following the primary vaccination (across doses) and during the 4-day (Days 0-3) period following the booster vaccination (post Booster) with the Synflorix™ vaccine
Number of Subjects With 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 activity. Grade 3 Irr./Fuss. = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (>) 40.0°C. Across doses= across the 2 doses of the Synflorix™ vaccine in the Synflorix I group and across the 3 doses of the Synflorix™ vaccine in the Synflorix II group.	During the 4-day (Days 0-3) period following the primary vaccination (across doses) and during the 4-day (Days 0-3) period following the booster vaccination (post Booster) with the Synflorix™ vaccine
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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.	Within the 31-day (Days 0-30) post-primary vaccination period, across doses
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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.	Within the 31-day (Days 0-30) post booster vaccination period
Number of Subjects With Serious Adverse Events	A 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 primary vaccination period
Number of Subjects With Serious Adverse Events	A 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 booster vaccination period

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Schuerman L et al. Population variability in antibody responses following pneumococcal conjugate vaccination: experience with the non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Schuerman L et al. Population variability of opsonophagocytic activity following 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate (PHiD-CV) vaccination more limited than antibody responses. Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Schuerman L et al. Prevention of invasive pneumococcal disease and meningitis with PHiD-CV when used according to a 2+1 schedule. Abstract presented at the Meningitis Research Foundation Conference (MRFC). London, UK, 11-12 November 2009.
• Silfverdal SA, Hogh B, Bergsaker MR, Skerlikova H, Lommel P, Borys D, Schuerman L. Immunogenicity of a 2-dose priming and booster vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine. Pediatr Infect Dis J. 2009 Oct;28(10):e276-82. doi: 10.1097/INF.0b013e3181b48ca3.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 25, 2007

Study Registration Dates

• First Submitted: March 24, 2006
• First Submitted That Met QC Criteria: March 24, 2006
• First Posted (Estimate): March 27, 2006

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: May 8, 2018
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Pneumococcal vaccine; Booster vaccination; Pneumococcal disease; Primary vaccination; Dose comparison
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 105539

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Study Protocol
   Information identifier: 105539
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 105539
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 105539
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 105539
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 105539
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 105539
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register