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Completed

NCT Number: NCT01144663

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

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.

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Key information

Conditions

Infections, Meningococcal Bacterial Infections Bacterial Infections and Mycoses Gram-Negative Bacterial Infections Infections Meningococcal Infections Meningococcal Vaccines Neisseriaceae Infections

Age range

6 week–12 week

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

GSK Investigational Site, Haabneeme, Estonia

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About this study

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Nimenrix™

Biological

4- or 3-dose intramuscular injection

Menjugate®

Biological

3-dose intramuscular injection

NeisVac-CTM

Biological

3-dose intramuscular injection

Infanrix™ hexa

Biological

4-dose intramuscular injection

Other names: Infanrix hexa™

Synflorix™

Biological

4-dose intramuscular injection

Primary outcomes

  1. 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.

    Time frame: One month after the final primary vaccination at Month 3

    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%.

  2. Number of Subjects With rSBA-MenC Antibody Titers ≥ the Cut-off Value

    Time frame: One month after the final primary vaccination at Month 3

    The cut-off value for rSBA-MenC titers was ≥ 1:8.

Secondary outcomes

  1. Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers Above Cut-off Values

    Time frame: Pre-primary vaccination at Month 0

    The cut-off values for rSBA-Men antibody titers were greater than or equal to (≥) 1:8 and ≥ 1:128 at pre-vaccination

  2. rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers

    Time frame: Pre-primary vaccination at Month 0

    Antibody titers were presented as geometric mean titers (GMTs).

  3. Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY Antibody Titers Above the Cut-off Values

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    The cut-off values for the rSBA-Men antibody titers were greater than or equal to (≥) 1:8 and ≥ 1:128.

  4. rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    Antibody titers were presented as geometric mean titers (GMTs).

  5. 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

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    The cut-off values for hSBA antibody titers were greater than or equal to (≥) 1:4 and ≥ 1:8.

  6. hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    Antibody titers were presented as geometric mean titers (GMTs).

  7. Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers Above the Cut-off Values

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    The cut-off values for hSBA antibody titers were greater than or equal to (≥) 1:4 and ≥ 1:8.

  8. hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    Antibody titers were presented as geometric mean titers (GMTs).

  9. Number of Subjects With Anti-pneumococcal Serotypes (Anti-P) Antibody Concentrations Above the Cut-off Values

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    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

  10. Anti-pneumococcal Serotypes Antibody Concentrations

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    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.

  11. Number of Subjects With Anti-pneumococcal Serotypes Antibody Concentrations Above the Cut-off Values

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    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

  12. Anti-pneumococcal Serotypes Antibody Concentrations

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    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.

  13. Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Concentrations ≥ the Cut-off Value

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    The cut-off value for anti-D and anti-T concentrations was greater than or equal to (≥) 0.1 IU/mL

  14. Anti-D and Anti-T Antibody Concentrations

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL).

  15. Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ the Cut-off Value

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    The cut-off value for anti-D and anti-T concentrations was greater than or equal to (≥) 0.1 IU/mL

  16. Anti-D and Anti-T Antibody Concentrations

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL).

  17. Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Concentrations ≥ the Cut-off Value

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    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).

  18. Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in EL.U/mL.

  19. Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Concentrations ≥ the Cut-off Value

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    The cut-off value for anti-PT, anti-FHA and anti-PRN concentrations was greater than or equal to (≥) 5 EL.U/mL.

  20. Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in EL.U/mL.

  21. Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Values

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    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.

  22. Anti-HBs Antibody Concentrations

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).

  23. Number of Subjects With Anti-HBs Antibody Concentrations Above the Cut-off Values

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    The cut-off values for anti-HBs concentrations were greater than or equal to (≥) 10 mIU/mL and ≥ 100 mIU/mL.

  24. Anti-HBs Antibody Concentrations

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).

  25. Number of Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Concentrations ≥ the Cut-off Values

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    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.

  26. Anti-PRP Antibody Concentrations

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL).

  27. Number of Subjects With Anti-PRP Antibody Concentrations Above the Cut-off Values

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    The cut-off values for anti-PRP antibody concentrations were greater than or equal to (≥) 0.15 µg/mL and ≥ 1.0 µg/mL.

  28. Anti-PRP Antibody Concentrations

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL).

  29. Number of Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentrations ≥ the Cut-off Value

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    The cut-off value for anti-poliovirus type 1, 2 and 3 antibody concentrations was greater than or equal to (≥) 1:8.

  30. Anti-polio Type 1, 2 and 3 Antibody Titers

    Time frame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3

    Antibody titers were presented as geometric mean titers (GMTs).

  31. Number of Subjects With Anti-polio Type 1, 2 and 3 Antibody Concentrations ≥ the Cut-off Value

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    The cut-off value for anti-poliovirus type 1, 2 and 3 antibody concentrations was greater than or equal to (≥) 1:8.

  32. Anti-polio Type 1, 2 and 3 Antibody Titers

    Time frame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11

    Antibody titers were presented as geometric mean titers (GMTs).

  33. Number of Subjects With Any and Grade 3 Solicited Local Symptoms

    Time frame: During the 8-day (Days 0-7) post-vaccination period following each dose and across doses from Day 0 to Month 3 (Primary 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. 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).

  34. Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-meningococcal Vaccination

    Time frame: 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)

    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.

  35. Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Infanrix™ Hexa Vaccination

    Time frame: 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)

    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.

  36. Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Synflorix Vaccination

    Time frame: 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)

    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.

  37. Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-meningococcal Vaccination

    Time frame: During the 8-day (Days 0-7) post-meningococcal booster vaccination period

    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.

  38. Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Infanrix™ Hexa Vaccination

    Time frame: During the 8-day (Days 0-7) post-Infanrix™ hexa booster vaccination period

    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.

  39. Number of Subjects With Any Unsolicited Adverse Events (AEs)

    Time frame: Within 31-days (Days 0-30) post-each primary vaccination dose

    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.

  40. Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Synflorix™ Vaccination

    Time frame: During the 8-day (Days 0-7) post-Synflorix™ booster vaccination period

    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.

  41. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

    Time frame: During the 8-day (Days 0-7) post-vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)

    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).

  42. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

    Time frame: During the 8-day (Days 0-7) post-booster vaccination period

    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.

  43. Number of Subjects With Any Unsolicited Adverse Events (AEs)

    Time frame: Within 31-days (Days 0-30) post-booster vaccination period

    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.

  44. Number of Subjects With Serious Adverse Events (SAEs)

    Time frame: Throughout the entire study (from Day 0 to Month 16)

    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.

  45. Number of Subjects With Serious Adverse Events (SAEs)

    Time frame: From Booster vaccination (Month 10) up to Extended Safety Follow-Up (ESFU) (Month 16)

    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.

  46. Number of Subjects With New Onset of Chronic Illnesses (NOCIs)

    Time frame: 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)

    NOCIs assessed included asthma, autoimmune disorders, type 1 diabetes and allergies.

  47. Number of Subjects With New Onset of Chronic Illnesses (NOCIs)

    Time frame: From Booster vaccination (Month 10 to Month 11) up to ESFU (Month 16)

    NOCIs assessed included asthma, autoimmune disorders, type 1 diabetes and allergies.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

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

Important dates

Study start
2010
Primary completion
2012
Study completion
2013
First posted
Jun 15, 2010
Registry last updated
Dec 31, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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