Immunogenicity and Safety of Havrix™ Co-Administered With a Diphtheria, Tetanus and Pertussis and a Haemophilus b Vaccine in Children Aged 15 Months

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00197236
First received: September 15, 2005
Last updated: April 11, 2013
Last verified: March 2011
  Purpose

This is a study to evaluate the immune response and safety of GSK Biologicals 2-dose inactivated hepatitis A vaccine when administered with a diphtheria, tetanus and pertussis combination (DTaP) vaccine and a Haemophilus influenza type B (Hib) vaccine in children 15 months of age. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.


Condition Intervention Phase
Hepatitis A Vaccine
Hepatitis A
Biological: Havrix™
Biological: Infanrix™
Biological: ActHIB™
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety of GSK Biologicals' Inactivated Hepatitis A Vaccine (Havrix™) Co-administered With GSK Biologicals' DTaP Vaccine (Infanrix™) and Aventis Pasteur's Haemophilus b Conjugate Vaccine (ActHIB) in Healthy Children 15 Months of Age

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the Second Dose of Havrix [ Time Frame: 31 days following the second dose of Havrix™ ] [ Designated as safety issue: No ]
    Subjects are defined as being anti-HAV seropositive if their anti-HAV antibody concentration is ≥ 15 milli-International Units per milliliter (mIU/mL).

  • Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects [ Time Frame: 31 days following the administration of Infanrix™ and ActHIB ] [ Designated as safety issue: No ]
    Subjects are defined as being anti-diphtheria, anti-tetanus and anti-PRP seroprotected if their anti-diphtheria and anti-tetanus antibody concentration is ≥ 0.1 International Units per milliliter (IU/mL) and if their anti-PRP antibody concentration is ≥ 1 microgram per milliliter (μg/mL), respectively.

  • Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN) [ Time Frame: 31 days following the administration of Infanrix™ and ActHIB ] [ Designated as safety issue: No ]
    Subjects are considered as being vaccine responders if they were initially seronegative and become seropositive (≥ 5 Enzyme Linked Immunosorbent Assay Units per Milliliter (EL.U/mL)), or were initially seropositive and have a 2-fold increase above pre-study concentrations.


Secondary Outcome Measures:
  • Anti-diphtheria and Anti-tetanus Antibody Geometric Mean Concentrations (GMC) [ Time Frame: 31 days following the administration of Infanrix™ and ActHIB ] [ Designated as safety issue: No ]
    GMCs are expressed as International Units per milliliter (IU/mL).

  • Anti-polyribosylribitol Phosphate (PRP) Antibody Geometric Mean Concentrations (GMC) [ Time Frame: 31 days following the administration of Infanrix™ and ActHIB ] [ Designated as safety issue: No ]
    GMCs are expressed as microgram/milliliter (µg/mL).

  • Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) [ Time Frame: 31 days following the administration of Infanrix™ and ActHIB ] [ Designated as safety issue: No ]
    Seropositivity is defined as antibody concentrations ≥ 5 Enzyme Linked Immunosorbent Assay Units per Milliliter (EL.U/mL) for anti-PT, anti-FHA and anti-PRN antibodies and as antibody concentrations ≥ 0.15 microgram/milliliter (µg/mL) for anti-PRP antibodies.

  • Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the First Dose of Havrix [ Time Frame: 31 days following the first dose of Havrix™ ] [ Designated as safety issue: No ]
    Subjects are defined as being anti-HAV seropositive if their anti-HAV antibody concentration is ≥ 15 milli-International Units per milliliter (mIU/mL).

  • Anti-hepatitis A Virus (HAV) Antibody Geometric Mean Concentrations (GMC) Following the First Dose of Havrix [ Time Frame: 31 days following the first dose of Havrix™ ] [ Designated as safety issue: No ]
    Anti-hepatitis A (HAV) antibody geometric mean concentrations (GMC) are expressed as milli-International Units per milliliter (mIU/mL).

  • Anti-hepatitis Virus A (HAV) Antibody Geometric Mean Concentrations (GMC) Following the Second Dose of Havrix [ Time Frame: 31 days following the second dose of Havrix™ ] [ Designated as safety issue: No ]
    Anti-hepatitis A (HAV) antibody geometric mean concentrations (GMC) are expressed as milli-International Units per milliliter (mIU/mL).

  • Number of Subjects With Vaccine Response to Havrix™. [ Time Frame: 31 days following the second dose ] [ Designated as safety issue: No ]
    Vaccine response to Havrix is defined as post-vaccination anti-HAV antibody concentrations ≥ 15 mIU/mL in initially seronegative subjects or a ≥ 2-fold increase above the pre-vaccination anti-HAV antibody concentration in initially seropositive subjects.

  • Number of Subjects Reporting Solicited Local Adverse Events (AEs) [ Time Frame: 4-day period following each dose of study vaccine(s) ] [ Designated as safety issue: No ]
    Solicited local AEs assessed include pain, redness and swelling. Data across doses are presented in the table.

  • Number of Subjects Reporting Solicited General Adverse Events (AEs) [ Time Frame: 4-day period following each dose of study vaccine(s) ] [ Designated as safety issue: No ]
    Solicited general AEs assessed include drowsiness, axillary fever ≥ 37.5°C, irritability and loss of appetite. Data across doses are presented in the table.

  • Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: 31-day period following each dose of study vaccine(s) ] [ Designated as safety issue: No ]
    An Adverse Event is 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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events [ Time Frame: Active Phase and the 6-months Extended Safety Follow-up (ESFU) Phase. ] [ Designated as safety issue: No ]
    Since the related information about medically significant events was not specifically collected and new chronic illnesses were only collected in the extended safety follow-up phase, all unsolicited adverse events (AEs) throughout the study are reported in the table without identifying which event was a medically significant or new chronic illness.


Enrollment: 468
Study Start Date: November 2003
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Havrix Group
Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9.
Biological: Havrix™
2 intramuscular injections, 6 months apart
Experimental: Infanrix + ActHIB→Havrix Group
Subjects received Infanrix co-administered with ActHIB at Day 0, followed by one dose of Havix at Day 30 and a second dose of Havrix at Month 7-10.
Biological: Havrix™
2 intramuscular injections, 6 months apart
Biological: Infanrix™
1 intramuscular injection
Biological: ActHIB™
1 intramuscular injection
Active Comparator: Havrix + Infanrix + ActHIB Group
Subjects received one dose of Havrix co-administered with Infanrix and ActHIB vaccines at Day 0 followed by a second dose of Havrix at Month 6-9.
Biological: Havrix™
2 intramuscular injections, 6 months apart
Biological: Infanrix™
1 intramuscular injection
Biological: ActHIB™
1 intramuscular injection

Detailed Description:

An open, controlled comparison of Havrix™ administered alone or with Infanrix™ and ActHIB. The three groups evaluated are: 1) Havrix™ alone, 2) Havrix™ + Infanrix™ and ActHIB and 3) Infanrix™ and ActHIB followed by Havrix™ one month later.

  Eligibility

Ages Eligible for Study:   12 Months to 13 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects whose parents/guardians are believed by the investigator to be willing to comply with the requirements of the protocol
  • A male or female child 12 or 13 months of age at the time of entry into the Enrolment Phase,
  • Subjects must have previously received three doses each of DTaP and Hib vaccines during the first year of life. The three doses of DTaP vaccine must have been administered as either Infanrix™ or Pediarix™ and the three doses of Hib vaccine must have been administered as ActHIB™, HibTITER™, OmniHIB™.
  • Subjects who, at 15 months of age, will have had at least six months elapse since their third dose of Infanrix™ or Pediarix™,
  • Written informed consent obtained from the parents or guardian of the subject,
  • Free of obvious health problems as established by medical history and history-directed physical examination before entering into the study, and
  • Parents/guardian of the subject must have a telephone or be able to be contacted by telephone.

Exclusion Criteria:

  • Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 31 days preceding the first dose of study vaccine, or planned use during the study period,
  • Chronic administration (defined as more than 14 days) of immuno-suppressant or other immune-modifying drugs within six months prior to vaccination or planned administration at any time during the study period.
  • Planned administration or administration of any vaccine not foreseen by the study protocol during the period 42 days before and 31 days after each dose of study vaccine(s).
  • Previous vaccination against DTaP using a commercially-available brand other than Infanrix™ or Pediarix™ or against Hib using a commercially-available brand other than ActHIB™, HibTITER™ or OmniHIB™.
  • Previous vaccination with more than three doses of DTaP-containing vaccines or more than three doses of Hib-containing vaccines.
  • Previous vaccination against hepatitis A,
  • History or known exposure to hepatitis A,
  • History of diphtheria, tetanus, pertussis and/or Haemophilus influenza type b,
  • Known exposure to diphtheria, tetanus, pertussis and/or Haemophilus influenza type b within 31 days prior to the start of the study,
  • History of non-response to any vaccine in the current routine immunization schedule,
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection,
  • A family history of congenital, hereditary or infectious immunodeficiency or parental risk factors for HIV infection,
  • History of allergic disease/reactions or hypersensitivity likely to be exacerbated by any component of Havrix™, Infanrix™ or ActHIB™ including 2-phenoxyethanol, neomycin and gelatin,
  • History of hypersensitivity/allergic reaction to latex
  • Major congenital defects or serious chronic illness,
  • History of any neurologic disorder
  • Acute disease at the time of vaccination.
  • Administration of immunoglobulins and/or any blood products within three months prior to the first dose of study vaccine or planned administration at any time during the entire study period, i.e., the Enrolment Phase, the Active Phase and the Extended Safety Follow-up Phase
  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: NCT00197236

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Trofa A et al. (2011) Immunogenicity and safety of an inactivated Hepatitis A vaccine when co-administered with Diphtheria-Tetanus-Acellular Pertussis and Haemophilus influenzae type b vaccines to children 15 months of age. Pediatr Infect Dis J. 30(9):e164-169.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00197236     History of Changes
Other Study ID Numbers: 208109/232
Study First Received: September 15, 2005
Results First Received: December 2, 2008
Last Updated: April 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Hepatitis A

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections

ClinicalTrials.gov processed this record on September 16, 2014