Study to Evaluate GSK Biologicals' GSK2197870A Vaccine Given as Primary Course in Infants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00871338
First received: March 26, 2009
Last updated: July 24, 2014
Last verified: June 2014
  Purpose

The purpose of this Phase II study is to evaluate the feasibility of GSK Biologicals' GSK2197870A vaccine co-administered with Wyeth-Lederle's Prevenar™ when given in healthy infants as a three-dose primary vaccination course at 2, 3 and 4 months of age followed by a booster dose of GSK Biologicals' Menitorix™ at 12 months of age.


Condition Intervention Phase
Neisseria Meningitidis
Haemophilus Influenzae Type b
Biological: GSK2197870A
Biological: Prevenar™
Biological: Menitorix™
Biological: Pediacel™
Biological: Menjugate™
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Study in Healthy Children of GSK Biologicals' DTPa-IPV/Hib-MenC-TT Vaccine, GSK2197870A, Co-administered With Prevenar™ as a Three-dose Primary Vaccination Course in Infancy Followed by a Booster Dose of Menitorix™ at 12 Months of Age

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Seroprotected Subjects for Anti-polyribosylribitol Phosphate (Anti-PRP). [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL).

  • Number of Seropositive Subjects Against Neisseria Meningitidis Using Baby Rabbit Complement (rSBA-MenC) [ Time Frame: At Month 2 and Month 3. ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a vaccinated subject who had rSBA-MenC ≥ 1:8.


Secondary Outcome Measures:
  • Number of Subjects With Anti-PRP Concentrations Antibody Above the Cut-off. [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    The reference cut-off was ≥ 1.0 micrograms per milliliter (µg/mL).

  • Number of Subjects With Anti-polysaccharide C (Anti-PSC ) Antibody Concentrations Above the Cut-offs. [ Time Frame: At Month 2 and Month 3. ] [ Designated as safety issue: No ]
    The reference cut-offs were ≥ 0.3 µg/mL and ≥ 2 µg/mL.

  • Number of Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. [ Time Frame: At Month 3. ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had anti-D and anti-T antibody concentrations ≥ 0.1 international units per milliliter (IU/mL).

  • Number of Seropositive Subjects Against Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN). [ Time Frame: At Month 3. ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a vaccinated subject who had anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliters (EL.U/mL).

  • Number of Seroprotected Subjects for Anti-poliovirus (Anti-polio) Types 1, 2 and 3. [ Time Frame: At Month 3. ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had anti-polio 1, 2 and 3 antibody concentrations ≥ 1:8.

  • Number of Seropositive Subjects for Anti-pneumococcal (Anti-PNE) Serotypes. [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a vaccinated subject who had anti- pneumococcal antibody concentrations ≥ 0.2 micrograms per milliliter (µg/mL). The anti-PNE serotypes assessed were 4, 6B, 9V, 14, 18C, 19F and 23F.

  • Concentrations for Anti-PRP. [ Time Frame: At Month 3. ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.15 µg/mL.

  • Titers for rSBA-MenC. [ Time Frame: At Month 2 and Month 3. ] [ Designated as safety issue: No ]
    Titers were expressed as geometric mean titers (GMCs). The seropositivity reference cut-off value was ≥ 1:8.

  • Concentrations for Anti-PSC. [ Time Frame: At Month 2 and Month 3. ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.3 µg/mL.

  • Concentrations for Anti-T and Anti-D. [ Time Frame: At Month 3. ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.1 IU/mL.

  • Concentrations for Anti-PT, Anti-FHA and Anti-PRN. [ Time Frame: At Month 3. ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seropositivity reference cut-off value was ≥ 5 EL.U/mL.

  • Titers for Anti-polio 1, 2 and 3. [ Time Frame: At Month 3. ] [ Designated as safety issue: No ]
    Titers were expressed as geometric mean titers (GMTs). The seropositivity reference cut-off value was ≥ 1:8.

  • Concentrations for Anti-PNE Serotypes. [ Time Frame: At Month 3. ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentreations (GMCs). The seropositivity reference cut-off value was ≥ 0.2 µg/mL.

  • Number of Seroprotected Subjects for Anti-PRP. [ Time Frame: At Month 10 and Month 11. ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL).

  • Number of Seropositive Subjects Against rSBA-MenC. [ Time Frame: At Month 10 and Month 11. ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a vaccinated subject who had rSBA-MenC ≥ 1:8.

  • Number of Subjects With Anti-PSC Antibody Concentrations Above the Cut-offs. [ Time Frame: At Month 10 and Month 11. ] [ Designated as safety issue: No ]
    The reference cut-offs were ≥ 0.3 µg/mL and ≥ 2 µg/mL.

  • Number of Seroprotive Subjects for Anti-D and Anti-T Antibodies. [ Time Frame: At Month 10. ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a vaccinated subject who had anti-D (ELISA) and anti-T antibody concentrations ≥ 0.1 IU/mL. Seropositivity for anti-D was also defined with the ≥ 0.016 IU/mL cut-off (Neutralisation assay).

  • Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN. [ Time Frame: At Month 10. ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a vaccinated subject who had anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliters (EL.U/mL).

  • Number of Seroprotected Subjects for Anti-anti-polio Types 1, 2 and 3. [ Time Frame: At Month 10. ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had anti-polio 1, 2 and 3 antibody concentrations ≥ 1:8.

  • Concentrations for Anti-PRP. [ Time Frame: At Month 10 and Month 11. ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.15 µg/mL.

  • Titers for rSBA-MenC. [ Time Frame: At Month 10 and Month 11. ] [ Designated as safety issue: No ]
    Titers were expressed as geometric mean titers (GMCs). The seropositivity reference cut-off value was ≥ 1:8.

  • Concentrations for Anti-PSC. [ Time Frame: At Month 10 and Month 11. ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.3 µg/mL.

  • Concentrations for Anti-T and Anti-D. [ Time Frame: At Month 10. ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.1 IU/mL. Seropositivity for anti-D was also defined with the ≥ 0.016 IU/mL cut-off (Neutralisation assay).

  • Concentrations for Anti-PT, Anti-FHA and Anti-PRN. [ Time Frame: At Month 10. ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seropositivity reference cut-off value was ≥ 5 EL.U/mL.

  • Titers for Anti-polio 1, 2 and 3. [ Time Frame: At Month 10. ] [ Designated as safety issue: No ]
    Titers were expressed as geometric mean titers (GMTs). The seroprotection reference cut-off value was ≥ 1:8.

  • Number of Subjects With a Booster Response to rSBA-MenC Antibodies. [ Time Frame: At Month 11 ] [ Designated as safety issue: No ]
    Booster response defined as: for initially seronegative subjects, antibody titre ≥ 1:32 at post-booster (Month 11); for initially seropositive subjects, antibody titres at post-booster ≥ 4 fold the pre-booster.

  • Number of Subjects With a Booster Response to Anti-PRP Antibodies. [ Time Frame: At Month 11 ] [ Designated as safety issue: No ]
    Booster response defined as: for initially seronegative subjects, antibody concentration ≥ 0.6 µg/mL at post-booster (Month 11); for initially seropositive subjects, antibody concentrations at post-booster ≥ 4 fold the pre-booster.

  • Number of Subjects With a Booster Response to Anti-PSC Antibodies. [ Time Frame: At Month 11 ] [ Designated as safety issue: No ]
    Booster response defined as: for initially seronegative subjects, antibody concentration ≥ 1.2 µg/mL at post-booster (Month 11); for initially seropositive subjects, antibody concentrations at post-booster ≥ 4 fold the pre-booster.

  • Number of Subjects Reporting Any Solicited Local Symptoms. [ Time Frame: During the 8-day (Days 0-7) ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade.

  • Number of Subjects Reporting Any Solicited General Symptoms. [ Time Frame: During the 8-day (Days 0-7) ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever [axillary temperature above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of any local symptom regardless of intensity grade.

  • Number of Subjects Reporting Any Unsolicited Adverse Events (AEs). [ Time Frame: Within the 31-day (Days 0-30) follow up period after vaccination. ] [ Designated as safety issue: No ]
    An unsolicited AE is any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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 = occurrence of an AE regardless of intensity grade or relationship to study vaccination.

  • Number of Subjects Reporting Any Serious Adverse Events (SAEs). [ Time Frame: During the entire study period (Month 0 to Month 11) ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization or results in disability/incapacity of a study subjects. Any SAE = any SAE regardless of assessment of relationship to study vaccination.


Enrollment: 284
Study Start Date: June 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2197870A Group
Subjects aged between and including 6 and 12 weeks of age at the time of first vaccination received 3 doses of GSK2197870A vaccine at Months 0, 1 and 2, 2 doses of Prevenar™ vaccine at Months 0 and 2 and a booster dose of Menitorix™ vaccine at Month 10. All vaccines were administered intramuscularly. GSK2197870A and Menitorix™ vaccines were administered in the right upper anterolateral thigh and Prevenar™ vaccine in the left upper anterolateral thigh.
Biological: GSK2197870A
3 doses given at 2, 3 and 4 months of age
Other Names:
  • GSK Biologicals' combined diphtheria
  • tetanus
  • acellular pertussis
  • polio
  • HiB and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine.
Biological: Prevenar™
3 co-administered doses, intramuscular into right thigh
Other Name: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine
Biological: Menitorix™
1 booster dose at 12 months of age
Other Name: GSK Biologicals' combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine.
Active Comparator: Pediacel Group
Subjects aged between and including 6 and 12 weeks of age at the time of first vaccination received 3 doses of Pediacel™ vaccine at Months 0, 1 and 2, 2 doses of Prevenar™ vaccine at Months 0 and 2, 2 doses of Menjugate™ vaccine at Months 1 and 2 and a booster dose of Menitorix™ at Month 10. All vaccines were administered intramuscularly. Pediacel™ and Menitorix™ vaccines were administered in the right upper anterolateral thigh and Prevenar™ vaccine in the left upper anterolateral thigh and Menjugate™ vaccine in the left lower anterolateral thigh.
Biological: Prevenar™
3 co-administered doses, intramuscular into right thigh
Other Name: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine
Biological: Menitorix™
1 booster dose at 12 months of age
Other Name: GSK Biologicals' combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine.
Biological: Pediacel™
3 doses given at 2, 3 and 4 months of age
Other Name: Sanofi-Pasteur-MSD's combined DTPa-inactivated polio-Haemophilus influenzae type b vaccine.
Biological: Menjugate™
2 doses given at 3 and 4 months of age
Other Name: Novartis' meningococcal serogroup C CRM197 protein conjugated vaccine.

Detailed Description:

This protocol posting has been updated following Protocol amendment 1, 11-February-2010; The Study design section is impacted by this amendment.

  Eligibility

Ages Eligible for Study:   6 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:

  • A male or female infant between, and including, 6 and 12 weeks of age at the time of the first vaccination.
  • Born after 36 to 42 weeks of gestation.
  • Subjects who the investigator believes that their parents/ guardians can and will comply with the requirements of the protocol should be enrolled in the study.
  • Written informed consent obtained from the parent or guardian of the subject.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:

  • Use of any investigational or non-registered product 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. For corticosteroids, this will mean prednisone, or equivalent, >= 0.5 mg/kg/day. Inhaled and topical steroids are allowed.
  • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
  • Administration of a vaccine not foreseen by the study protocol within 30 days prior to vaccination, or planned administration during the study period.
  • 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 .
  • Evidence of previous or intercurrent diphtheria, tetanus, pertussis, poliomyelitis, Hib, pneumococcal and/or group C meningococcal vaccination or disease.
  • History of seizures or progressive neurological disease (one episode of febrile convulsion does not constitute an exclusion criterion).
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
  • Major congenital defects or serious chronic illness.

The following condition is temporary or self limiting and a subject may be vaccinated once the condition has resolved and no other exclusion criteria are met:

• Current febrile illness or axillary temperature ≥37.5ºC or other moderate to severe illness within 24 hours of study vaccine administration

  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: NCT00871338

Locations
United Kingdom
GSK Investigational Site
Ely, Cambridgeshire, United Kingdom, CB7 4HF
GSK Investigational Site
Southampton, Hampshire, United Kingdom, SO16 6YD
GSK Investigational Site
Oxford, Oxfordshire, United Kingdom, OX3 7LJ
GSK Investigational Site
Bristol, United Kingdom, BS2 8AE
GSK Investigational Site
London, United Kingdom, SW17 0QT
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00871338     History of Changes
Other Study ID Numbers: 111709
Study First Received: March 26, 2009
Results First Received: June 26, 2014
Last Updated: July 24, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
combined
Vaccines

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 29, 2014