Primary & Booster Study to Evaluate the Immunogenicity and Safety of Menitorix Vaccine in Preterm Infants

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00586612
First received: December 21, 2007
Last updated: November 17, 2011
Last verified: November 2011
  Purpose

The purpose of this Phase IIIb study is to evaluate the immunogenicity, reactogenicity & safety of GSK Biologicals' Hib-MenC vaccine (Menitorix™) when co-administered with GSK Biologicals' DTPa-HBV-IPV vaccine (Infanrix™ penta) & Wyeth's 7-valent pneumococcal conjugate vaccine (Prevenar™) in preterm infants as a 3-dose primary vaccination course during the first 6 months of life (at 2, 4, 6 months of age) and of a booster dose of Menitorix™ when co-administered with GSK Biologicals' DTPa-IPV vaccine (Infanrix IPV) and Wyeth's Prevenar in the second year of life (16-18 months of age). The control is a group of full-term infants receiving the same vaccines. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.


Condition Intervention Phase
Haemophilus Influenzae Type b Disease
Hepatitis B
Meningococcal Serogroup C Disease
Biological: Menitorix™
Biological: Infanrix™ penta
Biological: Prevenar™
Biological: Infanrix™ IPV
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immunogenicity & Safety Study in Preterm & Full-term Infants of GSK Biologicals' Hib-MenC Vaccine, Menitorix™ Co-administered With Infanrix™ Penta & Prevenar™ at 2, 4, 6 Months & as a Booster With Infanrix™ IPV & Prevenar™ at 16-18 Months

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Micrograms Per Milliliter (µg/mL) [ Time Frame: One month after the third vaccination ] [ Designated as safety issue: No ]
    Anti-PRP antibody concentration greater than or equal to 0.15 µg/mL is indicative of protection.

  • Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to 1:8 [ Time Frame: One month after the third vaccination ] [ Designated as safety issue: No ]
    rSBA-MenC titer greater than or equal to 1:8 is indicative of protection.


Secondary Outcome Measures:
  • Number of Subjects With Anti-Polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to the Cut-off Values [ Time Frame: Before vaccination (at Day 0) ] [ Designated as safety issue: No ]
    Anti-PRP antibody cut-off values assessed include 0.15 micrograms per milliliter (µg/mL) and 1 µg/mL.

  • Number of Subject With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 1 Microgram Per Milliliter [ Time Frame: One month after the third vaccination ] [ Designated as safety issue: No ]
    Anti-PRP antibody cut-off value assessed include 1 microgram per milliliter (µg/mL).

  • Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values [ Time Frame: Before vaccination (at Day 0) ] [ Designated as safety issue: No ]
    rSBA-MenC titer cut-off values assessed include 1:8, 1:32 and 1:128.

  • Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values [ Time Frame: One month after the third vaccination ] [ Designated as safety issue: No ]
    rSBA-MenC titer cut-off values assessed include 1:32 and 1:128.

  • Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values [ Time Frame: Before vaccination (at Day 0) ] [ Designated as safety issue: No ]
    Anti-PSC antibody cut-off values assessed include 0.3 micrograms per milliliter (µg/mL) and 2 µg/mL.

  • Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values [ Time Frame: One month after the third dose ] [ Designated as safety issue: No ]
    Anti-PSC antibody cut-off values assessed include 0.3 micrograms per milliliter (µg/mL) and 2 µg/mL.

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values [ Time Frame: Before vaccination (at Day 0) ] [ Designated as safety issue: No ]
    Anti-HBs antibody cut-off values assessed include 10 milli-international units per milliliter (mIU/mL) and 100 mIU/mL.

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values [ Time Frame: One month after the third dose ] [ Designated as safety issue: No ]
    Anti-HBs antibody cut-off values assessed include 10 milli-international units per milliliter (mIU/mL) and 100 mIU/mL.

  • Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration [ Time Frame: Before vaccination (at Day 0) ] [ Designated as safety issue: No ]
    Anti-PRP and anti-PSC concentrations are given as geometric mean concentrations (GMCs) expressed micrograms per milliliter (µg/mL).

  • Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration [ Time Frame: One month after the third dose ] [ Designated as safety issue: No ]
    Anti-PRP and anti-PSC concentrations are given as geometric mean concentrations (GMCs) expressed micrograms per milliliter (µg/mL).

  • Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration [ Time Frame: Before vaccination (at Day 0) ] [ Designated as safety issue: No ]
    Anti-HBs concentrations are given as geometric mean concentrations (GMCs) expressed in milli-international units per milliliter (mIU/mL).

  • Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration [ Time Frame: One month after the third dose ] [ Designated as safety issue: No ]
    Anti-HBs concentrations are given as geometric mean concentrations (GMCs) expressed in milli-international units per milliliter (mIU/mL).

  • Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer [ Time Frame: Before vaccination (at Day 0) ] [ Designated as safety issue: No ]
    rSBA-MenC titers are given as geometric mean titers (GMTs).

  • Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer [ Time Frame: One month after the third dose ] [ Designated as safety issue: No ]
    rSBA-MenC titers are given as geometric mean titers (GMTs).

  • Number of Subjects Reporting Solicited Local Symptoms [ Time Frame: During the 4-day follow-up period after any primary vaccination dose ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed include pain, redness and swelling and are presented across doses.

  • Number of Subjects Reporting Solicited General Symptoms [ Time Frame: During the 4-day follow-up period after any primary vaccination dose ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed include drowsiness, fever, irritability/fussiness and loss of appetite and are presented across doses.

  • Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: Within 31 days after each primary vaccination ] [ Designated as safety issue: No ]
    Unsolicited AE covers any AE 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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: Throughout the entire primary vaccination phase ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

  • Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Migrogram Per Milliliter (µg/mL) [ Time Frame: Prior to (Month 14) and one month after the booster vaccination (Month 15) ] [ Designated as safety issue: No ]
    Anti-PRP antibody cut-off value assessed was 0.15 migrogram per milliliter (µg/mL).

  • Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 1.0 Migrogram Per Milliliter (µg/mL) [ Time Frame: Prior to (Month 14) and one month after the booster vaccination (Month 15) ] [ Designated as safety issue: No ]
    Anti-PRP antibody cut-off value assessed was 1.0 migrogram per milliliter (µg/mL).

  • Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values [ Time Frame: Prior to (Month 14) and one month after the booster vaccination (Month 15) ] [ Designated as safety issue: No ]
    rSBA-MenC titer cut-off values assessed include 1:8, 1:32 and 1:128.

  • Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to the Cut-off Values [ Time Frame: Prior to (Month 14) and one month after the booster vaccination (Month 15) ] [ Designated as safety issue: No ]
    Anti-PSC antibody cut-off values assessed include 0.3 micrograms per milliliter (µg/mL) and 2.0 µg/mL.

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to the Cut-off Values [ Time Frame: Prior to (Month 14) the booster vaccination ] [ Designated as safety issue: No ]

    Anti-HBs antibody cut-off values assessed include 10 milli-international units per milliliter (mIU/mL) and 100 mIU/mL.

    Note: the protocol planned an analysis on HBs after the booster dose, but this analysis was not performed as the vaccines administered as booster doses did not contain HBs component.


  • Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration [ Time Frame: Prior to (Month 14) and one month after the booster vaccination (Month 15) ] [ Designated as safety issue: No ]
    Anti-PRP and anti-PSC concentrations are given as geometric mean concentrations (GMCs) in micrograms per milliliter (µg/mL).

  • Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration [ Time Frame: Prior to (Month 14) the booster vaccination ] [ Designated as safety issue: No ]

    Anti-HBs concentrations are given as geometric mean concentrations (GMCs) in milli-international units per milliliter (mIU/mL).

    Note: Planned analysis in the protocol of HBs after the booster dose was not performed as booster vaccines did not contain HBs component.


  • Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer [ Time Frame: Prior to (Month 14) and one month after the booster vaccination (Month 15) ] [ Designated as safety issue: No ]
    rSBA-MenC titers are given as geometric mean titers (GMTs).

  • Number of Subjects Reporting Solicited Symptoms (Local and General) [ Time Frame: During the 4-day follow-up period following booster vaccination ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include drowsiness, fever, irritability/fussiness and loss of appetite.

  • Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: Within 31 days after the booster vaccination (month 15) ] [ Designated as safety issue: No ]
    Unsolicited AE covers any AE 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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: 31 days after last primary vaccination until administration of booster dose (Month 14) and from the administration of the booster dose until the end of the study (Month 15) ] [ Designated as safety issue: No ]

    SAEs assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

    Period 1 is defined as 31 days after last primary vaccination until administration of booster dose (Month 14).

    Period 2 is defined as the administration of the booster dose until the end of the study (Month 15).



Enrollment: 313
Study Start Date: December 2007
Study Completion Date: November 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Preterm group
Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Biological: Menitorix™
Intramuscular injection, 3 doses in the primary study and 1 dose in the Booster study.
Biological: Infanrix™ penta
Intramuscular injection, 3 doses in the primary study
Biological: Prevenar™
Intramuscular injection, 3 doses in the primary study and 1 dose in the Booster study.
Biological: Infanrix™ IPV
Intramuscular injection, 1 dose in the Booster study.
Active Comparator: Full-term group
Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Biological: Menitorix™
Intramuscular injection, 3 doses in the primary study and 1 dose in the Booster study.
Biological: Infanrix™ penta
Intramuscular injection, 3 doses in the primary study
Biological: Prevenar™
Intramuscular injection, 3 doses in the primary study and 1 dose in the Booster study.
Biological: Infanrix™ IPV
Intramuscular injection, 1 dose in the Booster study.

Detailed Description:

This multicenter study is open & consists of a primary & a booster phase. The study has 2 treatment groups (Preterm & Full-term) that will receive the same vaccinations; the Full-term group will be the active control. Four blood samples will be collected from all subjects for immunogenicity analyses; 2 in the primary phase at prior to the first vaccination and one month after the third vaccination and 2 in the booster phase at prior to booster dose and one month after booster dose.

  Eligibility

Ages Eligible for Study:   8 Weeks to 12 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

All subjects must satisfy the following criteria at study entry:

  • Subjects who 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 12 weeks of age at the time of the first vaccination.
  • Written informed consent obtained from the parent or guardian of the subject.

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

  • Born after a gestation period of less than or equal to 36 weeks (≤258 days).
  • Medically stable, i.e. do not require significant medical support or ongoing management for debilitating disease and have demonstrated a clinical course of sustained recovery.

All full-term subjects must satisfy the following criteria at study entry:

  • Born after a gestation period between and including 37 and 42 weeks (≥259 days and ≤294 days).
  • Free of obvious health problems as established by medical history and clinical examination before entering into the study.

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.
  • Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
  • Planned administration/ administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose of vaccine until the last study visit, except measles-mumps-rubella (MMR) and varicella vaccines which may be given according to local immunisation practices and except rotavirus oral vaccine which is allowed at anytime during the study after hospital discharge as per prescribing information.
  • Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, meningococcal serogroup C and or Streptococcus pneumoniae disease, with the exception of hepatitis B vaccine or BCG vaccine given in the first month of life according to the national recommendations (although BCG and hepatitis B vaccines should have been given outside a 30-day window from the first administration of study vaccines).
  • History of diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and or S. pneumoniae disease.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, based on medical history and physical examination.
  • A family history of congenital or hereditary immunodeficiency.
  • History of allergic disease or reactions 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.
  • Acute disease at the time of enrolment.
  • Administration of immunoglobulins (with the exception of monoclonal antibodies against respiratory syncytial virus [RSV]) and/or any blood products within one month (30 days) preceding the first dose of study vaccines.
  • Planned administration of immunoglobulins and/or any blood products during the active phase of the study.

Specific criteria for the booster part of the study (to be checked at Visit 5, study month 14):

  • History of diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and or S. pneumoniae disease.
  • Previous vaccination, except the study vaccines and hepatitis birth dose, against diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and or S. pneumoniae disease.
  • Previous booster vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and/or S. pneumoniae disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00586612

Locations
Spain
GSK Investigational Site
Bilbao, Spain, 48013
GSK Investigational Site
Burgos, Spain, 09005
GSK Investigational Site
Getafe, Spain, 28905
GSK Investigational Site
Madrid, Spain, 28047
GSK Investigational Site
Madrid, Spain, 28041
GSK Investigational Site
Malaga, Spain, 29010
GSK Investigational Site
Móstoles/Madrid, Spain, 28935
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Perez DM et al. Combined Haemophilus Influenzae type B-Neisseria Meningitidis serogroup C vaccine (HIB-MENC, Menitorix™ GlaxoSmithKline) is immunogenic in preterm infants. Abstract presented at the 28th Annual Meeting of European Society for Paediatric Infectious Diseases (ESPID). Nice, France, 4-8 May 2010.

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00586612     History of Changes
Other Study ID Numbers: 110215, 110217
Study First Received: December 21, 2007
Results First Received: December 17, 2009
Last Updated: November 17, 2011
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by GlaxoSmithKline:
Conjugate vaccine
Persistence
Hib vaccine
Combination vaccine
Meningococcal vaccine
Safety
Preterm/full-term infants
Immunogenicity

Additional relevant MeSH terms:
Hepatitis B
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human
Hepatitis
Liver Diseases
Digestive System Diseases
PENTA
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on October 16, 2014