Safety and Immunogenicity of New Formulations of GlaxoSmithKline Biologicals' DTPa-HBV-IPV/Hib Vaccine (GSK217744)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01248884
First received: November 24, 2010
Last updated: July 3, 2014
Last verified: May 2014
  Purpose

This study is designed to evaluate the safety and immunogenicity of new formulations of GSK Biologicals' DTPa-HBV-IPV/Hib vaccine (GSK217744) when administered as a primary vaccination course to healthy infants at 2, 3 and 4 months of age.


Condition Intervention Phase
Tetanus
Poliomyelitis
Hepatitis B
Haemophilus Influenzae Type b
Acellular Pertussis
Diphtheria
Biological: Infanrix hexa™
Biological: Prevenar 13®
Biological: GSK217744
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity of New Formulations of GlaxoSmithKline Biologicals' DTPa-HBV-IPV/Hib Vaccine (GSK217744) in Primary Infant Vaccination

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. [ Time Frame: At Months 0 and 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).

  • Concentrations for Anti-pertussis Toxoid (Anti-PT) and Anti-pertactin (Anti-PRN) Antibodies. [ Time Frame: At Months 0 and 3 ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliters (EL.U/mL).

  • Number of Seroprotected Subjects for Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibodies. [ 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 Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 10 and 100 Milli-International Units Per Milliliter (mIU/mL) [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.

  • Concentrations for Anti-HBs Antibodies ≥ 10 and 100 mIU/mL [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. Concentrations were expressed as geometric mean concentrations (GMCs) in milli-International units per milliliter (mIU/mL).


Secondary Outcome Measures:
  • Concentrations for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. [ Time Frame: At Months 0 and 3 ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was 0.1 IU/mL.

  • Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT) and Anti-pertactin (Anti-PRN) Antibodies. [ Time Frame: At Months 0 and 3 ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a vaccinated subject who had anti-PT and anti-PRN antibody concentrations ≥ 5 EL.U/mL.

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

  • 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 ≥ 0.15 micrograms per milliliter (µg/mL). The anti-PNE serotypes assessed were 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

  • Concentrations for Anti-PNE Antibodies. [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs). The seropositivity cut-off of the assay was 0.15 µg /mL. The anti-PNE serotypes assessed were 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

  • Number of Subjects With a Vaccine Response to PT and PRN. [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    Vaccine response defined as: for initially seronegative subjects, antibody concentration ≥ 5 EL.U/mL at 1 month post primary vaccination (Month 3); for initially seropositive subjects, antibody concentration at 1 month post primary vaccination (Month 3) ≥ 1 fold the pre-vaccination antibody concentration.

  • 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 local 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 3) ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. Any SAE = any SAE regardless of assessment of relationship to study vaccination.


Enrollment: 721
Study Start Date: December 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK217744 Group 1
Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation A vaccine, co-administered with Prevenar 13® at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13® vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.
Biological: Prevenar 13®
3 co-administered doses, intramuscular into right thigh
Other Name: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine
Biological: GSK217744
3 doses, intramuscular into left thigh
Experimental: GSK217744 Group 2
Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation B vaccine, co-administered with Prevenar 13® at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13® vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.
Biological: Prevenar 13®
3 co-administered doses, intramuscular into right thigh
Other Name: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine
Biological: GSK217744
3 doses, intramuscular into left thigh
Active Comparator: Infanrix hexa Group
Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of Infanrix hexa™ vaccine, co-administered with Prevenar 13® at 2, 3 and 4 months of age. The Infanrix hexa™ and Prevenar 13® vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.
Biological: Infanrix hexa™
3 doses, intramuscular into left thigh
Other Name: DTPa-HBV-IPV/Hib
Biological: Prevenar 13®
3 co-administered doses, intramuscular into right thigh
Other Name: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine

Detailed Description:

This Protocol Posting has been updated following Protocol Amendment 1, February 2011, leading to the update of the exclusion criteria.

  Eligibility

Ages Eligible for Study:   60 Days to 90 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • A male or female between, and including, 60 and 90 days of age at the time of the first vaccination.
  • Born after a gestation period of 37 to 42 weeks inclusive.
  • Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) can and will comply with the requirements of the protocol.
  • Written informed consent obtained from the parent(s)/ Legally Acceptable Representative(s) of the subject.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

  • Child in care.
  • Use of any investigational or non-registered product other than the study vaccines 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.
  • Administration of a vaccine not foreseen by the study protocol, within 30 days prior to the first study visit, or planned administration during the study period, with the exception of oral rotavirus vaccination which is allowed at any time during the study.
  • 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, polio, hepatitis B, Hib and/or pneumococcal vaccination or disease, with the exception of hepatitis B vaccination at birth.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • 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 neurological disorders or seizures.
  • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
  • Acute disease and/or fever at the time of enrolment.
  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: NCT01248884

Locations
Dominican Republic
GSK Investigational Site
Santo Domingo, Dominican Republic
GSK Investigational Site
Santo Domingo, Distrito Nacional, Dominican Republic
Finland
GSK Investigational Site
Espoo, Finland, 02100
GSK Investigational Site
Helsinki, Finland, 00100
GSK Investigational Site
Helsinki, Finland, 00930
GSK Investigational Site
Jarvenpaa, Finland, 04400
GSK Investigational Site
Kokkola, Finland, 67100
GSK Investigational Site
Kuopio, Finland, 70210
GSK Investigational Site
Lahti, Finland, 15140
GSK Investigational Site
Oulu, Finland, 90220
GSK Investigational Site
Pori, Finland, 28100
GSK Investigational Site
Seinajoki, Finland, 60100
GSK Investigational Site
Tampere, Finland, 33100
GSK Investigational Site
Turku, Finland, 20520
GSK Investigational Site
Vantaa, Finland, 01600
GSK Investigational Site
Vantaa, Finland, 01300
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01248884     History of Changes
Other Study ID Numbers: 113948
Study First Received: November 24, 2010
Results First Received: May 8, 2014
Last Updated: July 3, 2014
Health Authority: United States: Food and Drug Administration
Finland: FIMEA (Finnish Medicines Agency)

Keywords provided by GlaxoSmithKline:
combination vaccine
Primary vaccination

Additional relevant MeSH terms:
Hepatitis B
Poliomyelitis
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human
Hepatitis
Liver Diseases
Digestive System Diseases
Myelitis
Central Nervous System Viral Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Spinal Cord Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on September 30, 2014