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

August 29, 2012 updated by: Centers for Disease Control and Prevention
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

248

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Alaska Native Medical Center
      • Anchorage, Alaska, United States, 99501
        • Anchorage Neighborhood Health Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 6 months (Child)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • HAVRIX

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
concentration of antibody to hepatitis A virus
Time Frame: baseline and 1, 7, and 12 months post vax
Sera obtained at time of first hepatitis A vaccine dose (baseline) and 1, 7, and 12 months thereafter
baseline and 1, 7, and 12 months post vax

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
reported side effects and adverse events
Time Frame: day of vaccination and 3 days thereafter
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.
day of vaccination and 3 days thereafter
antibodies to routine childhood vaccinations
Time Frame: age 13 months
in a sample of study subjects from each group, blood drawn at age 13 months was tested for response to routine vaccinations.
age 13 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centers for Disease Control and Prevention

Collaborators

GlaxoSmithKline
Alaska Native Medical Center

Investigators

  • Principal Investigator: Brian McMahon, Alaska Native Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 1996

Primary Completion (Actual)

June 1, 2001

Study Completion (Actual)

June 1, 2001

Study Registration Dates

First Submitted

August 29, 2005

First Submitted That Met QC Criteria

August 29, 2005

First Posted (Estimate)

August 31, 2005

Study Record Updates

Last Update Posted (Estimate)

August 30, 2012

Last Update Submitted That Met QC Criteria

August 29, 2012

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDC-NCID-1358
  • U50/CCU022279

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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