Immunogenicity and Safety of Meningococcal Vaccine GSK 134612 Co-administered With Pneumococcal and DTPa-HBV-IPV/Hib Vaccines

Immunogenicity and Safety of GSK Biologicals' Meningococcal Vaccine (GSK 134612) When Co-administered With a Pneumococcal Conjugate Vaccine and Infanrix Hexa™ in Healthy Infants

The purpose of this study is to evaluate immunogenicity and safety of meningococcal conjugate vaccine GSK134612 compared to the licensed vaccines MenC-CRM197 and MenC-TT in infants of 2 months of age. Pneumococcal conjugate vaccine and DTPa-HBV-IPV/Hib vaccines will be co-administered.

Study Overview

• Status: Completed
• Conditions: Infections, Meningococcal; Meningococcal Vaccines
• Intervention / Treatment: Biological: Nimenrix™; Biological: Infanrix™ hexa; Biological: Synflorix™; Biological: Menjugate®; Biological: NeisVac-CTM

Detailed Description

The study consists of a primary vaccination phase and a booster vaccination phase. The Protocol Posting has been updated due to protocol amendment 2.

• Study Type: Interventional
• Enrollment (Actual): 2095
• Phase: Phase 3

Contacts and Locations

Study Locations

• Estonia
  • Haabneeme, Estonia, 74001
    • GSK Investigational Site
  • Tallinn, Estonia, 10117
    • GSK Investigational Site
  • Tallinn, Estonia, 10617
    • GSK Investigational Site
  • Tallinn, Estonia
    • GSK Investigational Site
  • Tartu, Estonia, 51014
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 13055
    • GSK Investigational Site
  • Berlin, Germany, 12157
    • GSK Investigational Site
  • Berlin, Germany, 14197
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Kehl, Baden-Wuerttemberg, Germany, 77694
      • GSK Investigational Site
    • Schwaebisch-Hall, Baden-Wuerttemberg, Germany, 74523
      • GSK Investigational Site
  • Bayern
    • Berchtesgaden, Bayern, Germany, 83471
      • GSK Investigational Site
    • Bindlach, Bayern, Germany, 95463
      • GSK Investigational Site
    • Gilching, Bayern, Germany, 82205
      • GSK Investigational Site
    • Kirchheim, Bayern, Germany, 85551
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 81241
      • GSK Investigational Site
    • Weilheim, Bayern, Germany, 82362
      • GSK Investigational Site
  • Hessen
    • Baunatal-Grossenritte, Hessen, Germany, 34225
      • GSK Investigational Site
    • Eschwege, Hessen, Germany, 37269
      • GSK Investigational Site
    • Vellmar, Hessen, Germany, 34246
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Detmold, Nordrhein-Westfalen, Germany, 32756
      • GSK Investigational Site
    • Kleve-Materborn, Nordrhein-Westfalen, Germany, 47533
      • GSK Investigational Site
    • Porta Westfalica, Nordrhein-Westfalen, Germany, 32457
      • GSK Investigational Site
    • Solingen, Nordrhein-Westfalen, Germany, 42719
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Frankenthal, Rheinland-Pfalz, Germany, 67227
      • GSK Investigational Site
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • GSK Investigational Site
    • Trier, Rheinland-Pfalz, Germany, 54290
      • GSK Investigational Site
    • Worms, Rheinland-Pfalz, Germany, 67547
      • GSK Investigational Site
  • Sachsen
    • Leipzig, Sachsen, Germany, 04178
      • GSK Investigational Site
    • Wurzen, Sachsen, Germany, 04808
      • GSK Investigational Site
  • Sachsen-Anhalt
    • Wanzleben, Sachsen-Anhalt, Germany, 39164
      • GSK Investigational Site
    • Weissenfels, Sachsen-Anhalt, Germany, 06667
      • GSK Investigational Site
  • Schleswig-Holstein
    • Flensburg, Schleswig-Holstein, Germany, 24937
      • GSK Investigational Site
  • Thueringen
    • Lobenstein, Thueringen, Germany, 07356
      • GSK Investigational Site
• Spain
  • Almería, Spain, 04009
    • GSK Investigational Site
  • Antequera/Málaga, Spain, 29200
    • GSK Investigational Site
  • Badalona, Spain, 08916
    • GSK Investigational Site
  • Blanes (Girona), Spain, 17300
    • GSK Investigational Site
  • Burgos, Spain, 09006
    • GSK Investigational Site
  • Ciudad Real, Spain, 13005
    • GSK Investigational Site
  • Manlleu, Spain, 08560
    • GSK Investigational Site
  • Sevilla, Spain, 41014
    • GSK Investigational Site
  • Valencia, Spain, 46026
    • GSK Investigational Site
  • Valladolid, Spain, 47012
    • GSK Investigational Site
  • Vic, Spain, 08500
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All subjects must satisfy ALL the following criteria at study entry:

• Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visit).
• A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination.
• Written informed consent obtained from the parent(s) 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 at least 36 weeks.

Exclusion Criteria:

• Child in care.
• 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.
• Extended administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone >= 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.
• 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) until 30 days after the last dose of vaccine(s) (i.e. booster dose), with the exception of rotavirus vaccine which can be administered at any time during the study, according to the national immunisation recommendations. MMR(V) vaccine, if recommended in national immunisation programs, can be given after the last blood sampling time point i.e. after Visit 6. Seasonal or pandemic influenza vaccine can be given at any time during the study, and according to the Summary of Product Characteristics and national recommendations.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis serogroups A, C, W-135 or Y with the exception of vaccines where the first dose may be given within the first two weeks of life according to the national recommendations (for example hepatitis B and BCG).
• History of, or intercurrent, diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b disease, pneumococcal and/or meningococcal disease.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Family history of congenital or hereditary immunodeficiency.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
• Major congenital defects or serious chronic illness.
• History of any neurologic disorders or seizures (history of a single, simple febrile seizure is permitted).
• Acute disease and/or fever at the time of enrolment. (Fever is defined as temperature ≥ 37.5°C (99.5°F) on oral, axillary or tympanic setting, or ≥ 38.0°C (100.4°F) on rectal setting).

(Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator).

- 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nimenrix 3 Group; Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 3 primary doses of Nimenrix™ vaccine at 2, 3 and 4 months of age, followed by a booster dose of Nimenrix™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 3, 4 and 12 months of age.	Biological: Nimenrix™; 4- or 3-dose intramuscular injection; Biological: Infanrix™ hexa; 4-dose intramuscular injection; Other Names: Infanrix hexa™; Biological: Synflorix™; 4-dose intramuscular injection
Experimental: Nimenrix 2 Group; Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of Nimenrix™ vaccine at 2 and 4 months of age, followed by a booster dose of Nimenrix™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age.	Biological: Nimenrix™; 4- or 3-dose intramuscular injection; Biological: Infanrix™ hexa; 4-dose intramuscular injection; Other Names: Infanrix hexa™; Biological: Synflorix™; 4-dose intramuscular injection
Active Comparator: Menjugate Group; Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of Menjugate® vaccine at 2 and 4 months of age, followed by a booster dose of Menjugate® vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age.	Biological: Infanrix™ hexa; 4-dose intramuscular injection; Other Names: Infanrix hexa™; Biological: Synflorix™; 4-dose intramuscular injection; Biological: Menjugate®; 3-dose intramuscular injection
Active Comparator: NeisVac-C Group; Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of NeisVac-C™ vaccine at 2 and 4 months of age, followed by a booster dose of NeisVac-C™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age.	Biological: Infanrix™ hexa; 4-dose intramuscular injection; Other Names: Infanrix hexa™; Biological: Synflorix™; 4-dose intramuscular injection; Biological: NeisVac-CTM; 3-dose intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Serum Bactericidal Assay Using Baby Rabbit Complement Against Meningococcal Serogroups A, W-135 and Y (rSBA-MenA, rSBA-MenW-135 and rSBA-Y) Antibody Titers Greater Than or Equal to (≥) the Cut-off Value.	The cut-off value for the rSBA-MenA, rSBA-MenW-135 and rSBA-Y titers was greater than or equal to (≥) 1:8. Indication of the immunogenicity of the 2-dose and 3-dose schedules: the lower limit of the two-sided exact 95% CI for the percentage of subjects with post-primary vaccination rSBA antibody titre ≥ 1:8 is greater than or equal to the pre-defined clinical limit of 80%.	One month after the final primary vaccination at Month 3
Number of Subjects With rSBA-MenC Antibody Titers ≥ the Cut-off Value	The cut-off value for rSBA-MenC titers was ≥ 1:8.	One month after the final primary vaccination at Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers Above Cut-off Values	The cut-off values for rSBA-Men antibody titers were greater than or equal to (≥) 1:8 and ≥ 1:128 at pre-vaccination	Pre-primary vaccination at Month 0
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers	Antibody titers were presented as geometric mean titers (GMTs).	Pre-primary vaccination at Month 0
Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY Antibody Titers Above the Cut-off Values	The cut-off values for the rSBA-Men antibody titers were greater than or equal to (≥) 1:8 and ≥ 1:128.	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers	Antibody titers were presented as geometric mean titers (GMTs).	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Number of Subjects With Serum Bactericidal Assay Using Human Complement Against Meningococcal Serogroups (hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY) Antibody Titers Above the Cut-off Values	The cut-off values for hSBA antibody titers were greater than or equal to (≥) 1:4 and ≥ 1:8.	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers	Antibody titers were presented as geometric mean titers (GMTs).	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers Above the Cut-off Values	The cut-off values for hSBA antibody titers were greater than or equal to (≥) 1:4 and ≥ 1:8.	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers	Antibody titers were presented as geometric mean titers (GMTs).	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Number of Subjects With Anti-pneumococcal Serotypes (Anti-P) Antibody Concentrations Above the Cut-off Values	The cut-off values for anti-1, anti-4, anti-5, anti-6B, anti-7F, anti-9V, anti-14, anti-18C, anti-19F and anti-23F concentrations were greater than or equal to (≥) 0.15 micrograms per milliliter (µg/mL) and ≥ 0.35 µg/mL	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Anti-pneumococcal Serotypes Antibody Concentrations	Anti-1, anti-4, anti-5, anti-6B, anti-7F, anti-9V, anti-14, anti-18C, anti-19F and anti-23F antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in µg/mL.	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Number of Subjects With Anti-pneumococcal Serotypes Antibody Concentrations Above the Cut-off Values	The cut-off values for anti-1, anti-4, anti-5, anti-6B, anti-7F, anti-9V, anti-14, anti-18C, anti-19F and anti-23F concentrations were ≥ 0.15 µg/mL and ≥ 0.35 µg/mL	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Anti-pneumococcal Serotypes Antibody Concentrations	Anti-1, anti-4, anti-5, anti-6B, anti-7F, anti-9V, anti-14, anti-18C, anti-19F and anti-23F antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in µg/mL.	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Concentrations ≥ the Cut-off Value	The cut-off value for anti-D and anti-T concentrations was greater than or equal to (≥) 0.1 IU/mL	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Anti-D and Anti-T Antibody Concentrations	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL).	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ the Cut-off Value	The cut-off value for anti-D and anti-T concentrations was greater than or equal to (≥) 0.1 IU/mL	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Anti-D and Anti-T Antibody Concentrations	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL).	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Concentrations ≥ the Cut-off Value	The cut-off value for anti-PT, anti-FHA and anti-PRN concentrations was greater than or equal to (≥) 5 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in EL.U/mL.	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Concentrations ≥ the Cut-off Value	The cut-off value for anti-PT, anti-FHA and anti-PRN concentrations was greater than or equal to (≥) 5 EL.U/mL.	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in EL.U/mL.	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Values	The cut-off values for anti-HBs concentrations were greater than or equal to (≥) 10 milli-international units per milliliter (mIU/mL) and ≥ 100 mIU/mL.	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Anti-HBs Antibody Concentrations	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Number of Subjects With Anti-HBs Antibody Concentrations Above the Cut-off Values	The cut-off values for anti-HBs concentrations were greater than or equal to (≥) 10 mIU/mL and ≥ 100 mIU/mL.	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Anti-HBs Antibody Concentrations	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Number of Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Concentrations ≥ the Cut-off Values	The cut-off values for anti-PRP antibody concentrations were greater than or equal to (≥) 0.15 micrograms per milliliter (µg/mL) and ≥ 1.0 µg/mL.	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Anti-PRP Antibody Concentrations	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL).	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Number of Subjects With Anti-PRP Antibody Concentrations Above the Cut-off Values	The cut-off values for anti-PRP antibody concentrations were greater than or equal to (≥) 0.15 µg/mL and ≥ 1.0 µg/mL.	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Anti-PRP Antibody Concentrations	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL).	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Number of Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentrations ≥ the Cut-off Value	The cut-off value for anti-poliovirus type 1, 2 and 3 antibody concentrations was greater than or equal to (≥) 1:8.	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Anti-polio Type 1, 2 and 3 Antibody Titers	Antibody titers were presented as geometric mean titers (GMTs).	Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
Number of Subjects With Anti-polio Type 1, 2 and 3 Antibody Concentrations ≥ the Cut-off Value	The cut-off value for anti-poliovirus type 1, 2 and 3 antibody concentrations was greater than or equal to (≥) 1:8.	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Anti-polio Type 1, 2 and 3 Antibody Titers	Antibody titers were presented as geometric mean titers (GMTs).	Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. For the Nimenrix 2, Menjugate and NeisVac-C groups, results corresponding to Dose 2 are for Infanrix hexa and Synflorix vaccination at Visit 2 (Month 1), while results corresponding to Dose 3 refer to the vaccination at Visit 3 (Month 2).	During the 8-day (Days 0-7) post-vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-meningococcal Vaccination	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.	During the 8-day (Days 0-7) post-meningococcal vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Infanrix™ Hexa Vaccination	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.	During the 8-day (Days 0-7) post-Infanrix hexa vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Synflorix Vaccination	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.	During the 8-day (Days 0-7) post-Synflorix vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-meningococcal Vaccination	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.	During the 8-day (Days 0-7) post-meningococcal booster vaccination period
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Infanrix™ Hexa Vaccination	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.	During the 8-day (Days 0-7) post-Infanrix™ hexa booster vaccination period
Number of Subjects With Any Unsolicited Adverse Events (AEs)	An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.	Within 31-days (Days 0-30) post-each primary vaccination dose
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Synflorix™ Vaccination	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.	During the 8-day (Days 0-7) post-Synflorix™ booster vaccination period
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature [defined as rectal temperature greater than or equal to (≥) 38 degrees Celsius (°C)]. Any = occurrence of any general symptoms, regardless of their intensity grade or relationship to study vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Not eating at all. Grade 3 Temperature= temperature above 40.0 (°C). Related = symptom assessed by the investigator as related to the vaccination. For the Nimenrix 2, Menjugate and NeisVac-C groups, results corresponding to Dose 2 are for Infanrix™ hexa and Synflorix™ vaccination at Visit 2 (Month 1), while results corresponding to Dose 3 refer to the vaccination at Visit 3 (Month 2).	During the 8-day (Days 0-7) post-vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature [defined as rectal temperature greater than or equal to (≥) 38 degrees Celsius (°C)]. Any = occurrence of any general symptoms, regardless of their intensity grade or relationship to study vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Not eating at all. Grade 3 Temperature= temperature above 40.0 (°C). Related = symptom assessed by the investigator as related to the vaccination.	During the 8-day (Days 0-7) post-booster vaccination period
Number of Subjects With Any Unsolicited Adverse Events (AEs)	An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.	Within 31-days (Days 0-30) post-booster vaccination period
Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	Throughout the entire study (from Day 0 to Month 16)
Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	From Booster vaccination (Month 10) up to Extended Safety Follow-Up (ESFU) (Month 16)
Number of Subjects With New Onset of Chronic Illnesses (NOCIs)	NOCIs assessed included asthma, autoimmune disorders, type 1 diabetes and allergies.	During 31-days (Days 0-30) post-each primary vaccination dose (Day 0 to Month 3) and from primary vaccination up to ESFU (Month 16)
Number of Subjects With New Onset of Chronic Illnesses (NOCIs)	NOCIs assessed included asthma, autoimmune disorders, type 1 diabetes and allergies.	From Booster vaccination (Month 10 to Month 11) up to ESFU (Month 16)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Merino Arribas JM, Carmona Martinez A, Horn M, Perez Porcuna XM, Otero Reigada MD, Mares Bermudez J, Centeno Malfaz F, Miranda M, Mendez M, Garcia Cabezas MA, Wittermann C, Bleckmann G, Fischbach T, Kolhe D, van der Wielen M, Baine Y. Safety and Immunogenicity of the Quadrivalent Meningococcal Serogroups A, C, W and Y Tetanus Toxoid Conjugate Vaccine Coadministered With Routine Childhood Vaccines in European Infants: An Open, Randomized Trial. Pediatr Infect Dis J. 2017 Apr;36(4):e98-e107. doi: 10.1097/INF.0000000000001484.
• Merino Arribas JM, Carmona Martinez A, Horn M, Perez Porcuna XM, Otero Reigada MDC, Mares Bermudez J, Centeno Malfaz F, Miranda M, Mendez M, Garcia Cabezas MA, Christoph W, Bleckmann G, Fischbach T, Kolhe D, Van der Wielen M, Baine Y. Immunogenicity and Reactogenicity of DTPa-HBV-IPV/Hib and PHiD-CV When Coadministered With MenACWY-TT in Infants: Results of an Open, Randomized Trial. Pediatr Infect Dis J. 2018 Jul;37(7):704-714. doi: 10.1097/INF.0000000000002061.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2010
• Primary Completion (Actual): June 22, 2012
• Study Completion (Actual): September 10, 2013

Study Registration Dates

• First Submitted: June 3, 2010
• First Submitted That Met QC Criteria: June 14, 2010
• First Posted (Estimate): June 15, 2010

Study Record Updates

• Last Update Posted (Actual): December 31, 2020
• Last Update Submitted That Met QC Criteria: December 3, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: immunogenicity; Infants; co-administration; non-inferiority; conjugate vaccine; meningococcal vaccine
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningococcal Infections
• Other Study ID Numbers: 113369; 2009-016841-24 (EudraCT Number)