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

Phase 3

Completed

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

• Registration Number: NCT00307034
• Lead Sponsor: GlaxoSmithKline

Brief Summary

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)

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2006-01-01
• Study First Submitted: 2006-03-24
• Study First Submitted QC: 2006-03-24
• Study First Posted: 2006-03-27
• Primary Completion: 2007-01-01
• Study Completion: 2007-01-25
• Results First Submitted: 2016-12-13
• Status Verified: 2017-02
• Results First Submitted QC: 2017-02-16
• Results First Posted: 2017-04-04
• Last Update Submitted: 2018-05-08
• Last Update Posted: 2018-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 351

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2-dose group	GSK Biologicals' 10-valent pneumococcal conjugate vaccine.	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.
2-dose group	Infanrix hexa.	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.
2-dose group	Infanrix-IPV/Hib.	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.
Comparator group	GSK Biologicals' 10-valent pneumococcal conjugate vaccine.	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.
Comparator group	Infanrix-IPV/Hib.	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.
Comparator group	Infanrix hexa.	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.

Primary Outcome Measures

Name	Time	Method
Number of Seroprotected Subjects Against Pneumococcal Serotypes	One month post-dose 2 (Month 3) administration of Synflorix™ vaccine	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.

Secondary Outcome Measures

Name	Time	Method
Number of Seroprotected Subjects Against Pneumococcal Serotypes	One month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine	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).
Antibody Concentrations Against Pneumococcal Serotypes	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	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.
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes	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	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.
Antibody Concentrations Against Protein D (Anti-PD)	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	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.
Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs)	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	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.
Antibody Titers Against Polio Type 1, 2 and 3 (Anti-polio 1, 2 and 3)	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	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.
Antibody Concentrations Against Diphteria (Anti-D) and Tetanus (Anti-T) Toxoids	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	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.
Antibody Concentrations Against Polyribosyl Ribitol Phosphate (Anti-PRP)	One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) booster dose of Synflorix™ vaccine	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.
Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA) and Pertactin (Anti-PRN)	One month post-dose 2 (Month 3) administration, one month before (Month 9) and after (Month 10) the booster dose of Synflorix™ vaccine	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.
Number of Subjects With Booster Vaccine Response to Anti-PT, Anti-FHA and Anti-PRN Antibodies	One month after (Month 9) the administration of the booster dose of Synflorix™ vaccine	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.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	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	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.
Number of Subjects With Unsolicited Adverse Events	Within the 31-day (Days 0-30) post booster vaccination period	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.
Number of Subjects With Serious Adverse Events	During the booster vaccination period	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.
Number of Subjects With Solicited General Symptoms	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	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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇸🇪 Örebro, Sweden