Immunogenicity Study of an Inactivated Hepatitis A Vaccine in Infants and Young Children

This study has been completed.
Sponsor:
Collaborators:
Alaska Native Medical Center
GlaxoSmithKline
Information provided by:
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT00139113
First received: August 29, 2005
Last updated: August 29, 2012
Last verified: August 2012
  Purpose

Infants born to immune mothers and therefore having passively-transferred maternal antibody (PMA) to hepatitis A virus (HAV) have a blunted immune response to hepatitis A vaccine. We compared the immunogenicity of hepatitis A vaccine among infants with and without PMA, vaccinated on different schedules. We found that when vaccination is begun at or after 12 months of age, there was no difference in the immune response to the vaccine between infants born to immune vs. susceptible mothers.


Condition Intervention Phase
Hepatitis A
Biological: hepatitis A vaccine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Immunogenicity Study of an Inactivated Hepatitis A Vaccine in Infants and Young Children

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • concentration of antibody to hepatitis A virus [ Time Frame: baseline and 1, 7, and 12 months post vax ] [ Designated as safety issue: No ]
    Sera obtained at time of first hepatitis A vaccine dose (baseline) and 1, 7, and 12 months thereafter


Secondary Outcome Measures:
  • reported side effects and adverse events [ Time Frame: day of vaccination and 3 days thereafter ] [ Designated as safety issue: Yes ]
    at time of each vaccine dose, parent was given a diary card on which to record systemic and injection site signs and symptoms observed on day of vaccination and subsequent 3 days.

  • antibodies to routine childhood vaccinations [ Time Frame: age 13 months ] [ Designated as safety issue: No ]
    in a sample of study subjects from each group, blood drawn at age 13 months was tested for response to routine vaccinations.


Enrollment: 248
Study Start Date: September 1996
Study Completion Date: June 2001
Primary Completion Date: June 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HAVRIX 6 and 12 mos; mother antibody pos
HAVRIX administered to infants born to anti-HAV positive mothers at ages 6 and 12 months
Biological: hepatitis A vaccine
2 doses of inactivated hepatitis A vaccine manufactured by GSK in licensed pediatric formulation of 720 EL. U. per dose given on 3 different schedules: aged 6 and 12 months, 12 and 18 months, and 15 and 21 months. Within each group, subjects were randomized to achieve a relatively equal number of children born to anti-HAV positive and anti-HAV negative mothers.
Other Name: HAVRIX
Active Comparator: HAVRIX age 6, 12 mos; mom antibody neg
HAVRIX administered to infants born to anti-HAV negative mothers at ages 6 and 12 months
Biological: hepatitis A vaccine
2 doses of inactivated hepatitis A vaccine manufactured by GSK in licensed pediatric formulation of 720 EL. U. per dose given on 3 different schedules: aged 6 and 12 months, 12 and 18 months, and 15 and 21 months. Within each group, subjects were randomized to achieve a relatively equal number of children born to anti-HAV positive and anti-HAV negative mothers.
Other Name: HAVRIX
Experimental: HAVRIX ages 12, 15 mos; mom antibody +
HAVRIX administered to infants born to anti-HAV positive mothers at ages 12 and 15 months
Biological: hepatitis A vaccine
2 doses of inactivated hepatitis A vaccine manufactured by GSK in licensed pediatric formulation of 720 EL. U. per dose given on 3 different schedules: aged 6 and 12 months, 12 and 18 months, and 15 and 21 months. Within each group, subjects were randomized to achieve a relatively equal number of children born to anti-HAV positive and anti-HAV negative mothers.
Other Name: HAVRIX
Active Comparator: HAVRIX ages 12, 15 mos; mom antibody-
HAVRIX administered to infants born to anti-HAV negative mothers at ages 12 and 15 months
Biological: hepatitis A vaccine
2 doses of inactivated hepatitis A vaccine manufactured by GSK in licensed pediatric formulation of 720 EL. U. per dose given on 3 different schedules: aged 6 and 12 months, 12 and 18 months, and 15 and 21 months. Within each group, subjects were randomized to achieve a relatively equal number of children born to anti-HAV positive and anti-HAV negative mothers.
Other Name: HAVRIX
Experimental: HAVRIX ages 15,21 mos; mom antibody +
HAVRIX administered to infants born to anti-HAV positive mothers at ages 15 and 21 months
Biological: hepatitis A vaccine
2 doses of inactivated hepatitis A vaccine manufactured by GSK in licensed pediatric formulation of 720 EL. U. per dose given on 3 different schedules: aged 6 and 12 months, 12 and 18 months, and 15 and 21 months. Within each group, subjects were randomized to achieve a relatively equal number of children born to anti-HAV positive and anti-HAV negative mothers.
Other Name: HAVRIX
Active Comparator: HAVRIX ages 15,21 mos; mom antibody -
HAVRIX administered to infants born to anti-HAV negative mothers at ages 15 and 21 months
Biological: hepatitis A vaccine
2 doses of inactivated hepatitis A vaccine manufactured by GSK in licensed pediatric formulation of 720 EL. U. per dose given on 3 different schedules: aged 6 and 12 months, 12 and 18 months, and 15 and 21 months. Within each group, subjects were randomized to achieve a relatively equal number of children born to anti-HAV positive and anti-HAV negative mothers.
Other Name: HAVRIX

Detailed Description:

Background: Infants with passively-transferred maternal antibody (PMA) to hepatitis A virus (HAV) have a blunted immune response to hepatitis A vaccine. We compared the immunogenicity of hepatitis A vaccine among infants with and without PMA, vaccinated on different schedules.

Methods: Infants were randomized to one of three groups, each receiving two doses of 720 EL.U. of hepatitis A vaccine (HAVRIX, Glaxo SmithKline) according to the following schedules: Group 1 at ages 6 and 12 months; Group 2 at ages 12 and 18 months; Group 3 at ages 15 and 21 months. We determined antibody to HAV (anti-HAV) status of mothers at the time of delivery, and measured infants' anti-HAV concentrations at the time of the first vaccine dose (baseline), and at 1, 7 and 12 months thereafter. Anti-HAV concentrations > 33 milli-International Units/milliliter (mIU/mL) were considered protective. We monitored adverse reactions using diary cards and chart reviews.

Results: A total of 239 infants were enrolled, including 134 born to anti-HAV negative mothers (Groups 1N, 2N, 3N) and 105 born to anti-HAV positive mothers (Groups 1P, 2P, 3P).

At month 12, 6 months after the second vaccine dose, the difference in GMC between Groups 1P and 1N was the only statistically significant difference within groups (p<0.05). There were no statistically significant differences in GMC among groups of infants born to anti-HAV negative mothers ("N" groups), but the difference between Group 1P and Group 3P infants was significant (p < 0.05). No serious adverse reactions related to vaccination were detected.

Conclusions: Hepatitis A vaccine is immunogenic among infants born to anti-HAV negative mothers, and among those born to anti-HAV positive mothers and vaccinated beginning as young as 12 months old. The persistence of PMA for at least six months among the majority of infants born to anti-HAV positive mothers results in lower seroconversion rates and GMC's.

  Eligibility

Ages Eligible for Study:   up to 6 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:term infant with normal growth and development, considered to be healthy at age 6 months; written informed consent by parent/guardian -

Exclusion Criteria:received or expected to receive immune globulin or blood/blood products while enrolled; received or expected to receive immunosuppressive therapy within 30 days of vaccination or has immune deficiency; currently enrolled in another vaccine trial; progressive or unstable neurological disorder

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  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00139113

Locations
United States, Alaska
Alaska Native Medical Center
Anchorage, Alaska, United States, 99508
Anchorage Neighborhood Health Center
Anchorage, Alaska, United States, 99501
Sponsors and Collaborators
Alaska Native Medical Center
GlaxoSmithKline
Investigators
Principal Investigator: Brian McMahon Alaska Native Medical Center
  More Information

Publications:
Responsible Party: Brian McMahon, Alaska Native Medical Center
ClinicalTrials.gov Identifier: NCT00139113     History of Changes
Other Study ID Numbers: CDC-NCID-1358, U50/CCU022279
Study First Received: August 29, 2005
Last Updated: August 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Centers for Disease Control and Prevention:
hepatitis A
hepatitis A vaccine

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

ClinicalTrials.gov processed this record on October 21, 2014