Safety and Immunogenicity of a Booster Dose 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:
NCT01453998
First received: October 6, 2011
Last updated: July 24, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to assess the immunogenicity, safety and reactogenicity of the booster vaccine dose of 2 new formulations of DTPa-HBV-IPV/Hib administered between 12 and 15 months of age, and the immune persistence following the primary series. All children in this booster study received a primary vaccination at 2, 3 and 4 months of age in study 113948 (NCT01248884). No new subjects will be enrolled in this booster study.


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

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

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: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) ] [ 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-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. [ Time Frame: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) ] [ 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 Seroprotected Subjects for Anti-polyribosyl-ribitol Phosphate (Anti-PRP) [ Time Frame: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) ] [ 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).

  • Concentrations for Anti-PRP Antibodies [ Time Frame: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) ] [ 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 Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies [ Time Frame: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) ] [ 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-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies [ Time Frame: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) ] [ 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 Seroprotected Subjects for Anti-polyribosyl-ribitol Phosphate (Anti-PRP). [ Time Frame: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) ] [ 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).

  • Concentrations for Anti-PRP Antibodies. [ Time Frame: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) ] [ 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 Seroprotected Subjects for Anti-poliovirus Types 1, 2 and 3. [ Time Frame: One month after the booster dose ] [ Designated as safety issue: No ]
  • Number of Seroprotected Subjects for Anti-Pertussis Toxoid. [ Time Frame: One month after the booster dose ] [ Designated as safety issue: No ]
  • Concentrations for Anti-poliovirus Types 1, 2 and 3 [ Time Frame: One month after the booster dose ] [ Designated as safety issue: No ]
  • Concentrations for Anti-Pertussis Toxoid. [ Time Frame: One month after the booster dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Seropositive Subjects for Anti-pneumococcal (Anti-PNE) Serotypes. [ Time Frame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) ] [ 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: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) ] [ 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 Seropositive Subjects for Anti-pneumococcal (Anti-PNE) Serotypes [ Time Frame: 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) ] [ 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: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) ] [ 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 Reporting Any Solicited Local Symptoms. [ Time Frame: During the 4-day (Days 0-3) post-vaccination period. (subjects enrolled before protocol amendment 2) ] [ 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 4-day (Days 0-3) post-vaccination period. (subjects enrolled before protocol amendment 2) ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were drowsiness, irritability/fussiness, 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. (subjects enrolled before protocol amendment 2) ] [ 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 (Days 0-30). (subjects enrolled before protocol amendment 2) ] [ 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.

  • Number of Subjects Reporting Any Solicited Local Symptoms [ Time Frame: During the 4-day (Days 0-3) post-vaccination period. (subjects enrolled after protocol amendment 2) ] [ 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 4-day (Days 0-3) post-vaccination period. (subjects enrolled after protocol amendment 2) ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were drowsiness, irritability/fussiness, 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. (subjects enrolled after protocol amendment 2) ] [ 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 (Days 0-30). (subjects enrolled after protocol amendment 2) ] [ 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: 657
Study Start Date: October 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK217744 Group 1
Subjects aged between and including 12 and 15 months at the time of booster vaccination who received the GSK217744 formulation A vaccine in the primary study and a booster dose of either GSK217744 formulation A vaccine (for subjects vaccinated before Protocol Amendment 2) or Infanrix hexa™ vaccine (for subjects vaccinated after Protocol Amendment 2) in this study, coadministered with a booster dose of Prevenar 13®. The Infanrix hexa™/GSK217744 and Prevenar 13® vaccines were administered intramuscularly into the right and left sides of the thigh, respectively.
Biological: Infanrix hexa™
Single dose, licensed formulation, intramuscular into right thigh
Other Name: DTPa-HBV-IPV/Hib
Biological: Prevenar 13®
Single co-administered dose, intramuscular into left thigh
Other Name: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine
Biological: GSK217744
Single dose, investigational formulation A or B, intramuscular into right thigh
Experimental: GSK217744 Group 2
Subjects aged between and including 12 and 15 months at the time of booster vaccination who received the GSK217744 formulation B vaccine in the primary study and a booster dose of either GSK217744 formulation B vaccine (for subjects vaccinated before Protocol Amendment 2) or Infanrix hexa™ vaccine (for subjects vaccinated after Protocol Amendment 2) in this study, coadministered with a booster dose of Prevenar 13®. The Infanrix hexa™/GSK217744 and Prevenar 13® vaccines were administered intramuscularly into the right and left sides of the thigh, respectively.
Biological: Infanrix hexa™
Single dose, licensed formulation, intramuscular into right thigh
Other Name: DTPa-HBV-IPV/Hib
Biological: Prevenar 13®
Single co-administered dose, intramuscular into left thigh
Other Name: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine
Biological: GSK217744
Single dose, investigational formulation A or B, intramuscular into right thigh
Active Comparator: Infanrix hexa Group
Subjects aged between and including 12 and 15 months at the time of booster vaccination who received the Infanrix hexa™ vaccine in the primary study and a booster dose of Infanrix hexa™ in this study, co-administered with a booster dose of Prevenar 13®. The Infanrix hexa™ and Prevenar 13® vaccines were administered intramuscularly into the right and left sides of the thigh, respectively.
Biological: Infanrix hexa™
Single dose, licensed formulation, intramuscular into right thigh
Other Name: DTPa-HBV-IPV/Hib
Biological: Prevenar 13®
Single co-administered dose, intramuscular into left thigh
Other Name: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine

  Eligibility

Ages Eligible for Study:   12 Months to 15 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who participated in the study 113948 (NCT01248884) and received three doses of the new or licensed DTPa-HBV-IPV/Hib study vaccine.
  • A male or female child between, and including, 12 and 15 months of age at the time of the booster vaccination.
  • Subjects who the investigator believes that parent(s)/ Legally Acceptable Representative(s) (LAR(s)) can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visit).
  • Written informed consent obtained from the parent(s)/LAR(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 (drug or vaccine) other than the study vaccines within 30 days preceding the booster dose of study vaccine, or planned use during the study period.
  • Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the booster dose.
  • Administration of a vaccine not foreseen by the study protocol within 30 days prior to vaccination, or planned administration during the study period.
  • Participation in another clinical study within three months prior to enrolment in the present booster study or at any time during the present booster study, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
  • Evidence of previous or intercurrent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Hib vaccination or disease since the conclusion visit of study 113948 (NCT01248884).
  • Serious chronic illness.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
  • History of any neurological disorders or seizures.
  • Administration of immunoglobulins and/or any blood products within the 3 months preceding the booster dose of study vaccine or planned administration during the study period.
  • Occurrence of any of the following events following previous administration of the study vaccine constitutes an absolute contraindication to further dosing.

    • Anaphylactic or other hypersensitivity reaction.
    • Encephalopathy defined as an acute, severe central nervous system disorder occurring within 7 days following vaccination and generally consisting of major alterations in consciousness, unresponsiveness, generalized or focal seizures that persist more than a few hours, with failure to recover within 24 hours.
    • Temperature of ≥ 40.0°C (axillary) or 40.5°C (rectal) within 48 hours of vaccination, not due to another identifiable cause.
    • Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of vaccination.
    • Persistent, inconsolable crying occurring within 48 hours of vaccination and lasting ≥ 3 hours.
    • Seizures with or without fever occurring within 3 days of vaccination.

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

• Acute disease and/or fever at the time of enrolment.

  • Fever is defined as temperature ≥ 37.5°C on oral, axillary or tympanic setting, or ≥ 38.0° 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.
  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: NCT01453998

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, 00930
GSK Investigational Site
Helsinki, Finland, 00100
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: NCT01453998     History of Changes
Other Study ID Numbers: 114843, 2011-000876-33
Study First Received: October 6, 2011
Results First Received: May 1, 2014
Last Updated: July 24, 2014
Health Authority: Finland: FIMEA (Finnish Medicines Agency)

Additional relevant MeSH terms:
Diphtheria
Hepatitis
Hepatitis A
Hepatitis B
Influenza, Human
Whooping Cough
Poliomyelitis
Tetanus
Corynebacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Orthomyxoviridae Infections
Respiratory Tract Infections
Respiratory Tract Diseases
Bordetella Infections
Gram-Negative Bacterial Infections
Infection
Myelitis
Central Nervous System Viral Diseases
Central Nervous System Infections

ClinicalTrials.gov processed this record on August 19, 2014