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

NCT ID: NCT00139113

Last Updated: 2024-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 248 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-09-30
• Study Completion Date: 2001-06-30

Brief Summary

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.

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.

Conditions

Hepatitis A

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

HAVRIX 6 and 12 mos; mother antibody pos

HAVRIX administered to infants born to anti-HAV positive mothers at ages 6 and 12 months

Group Type: EXPERIMENTAL

hepatitis A vaccine

Intervention Type: BIOLOGICAL

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.

HAVRIX age 6, 12 mos; mom antibody neg

HAVRIX administered to infants born to anti-HAV negative mothers at ages 6 and 12 months

Group Type: ACTIVE_COMPARATOR

hepatitis A vaccine

Intervention Type: BIOLOGICAL

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.

HAVRIX ages 12, 15 mos; mom antibody +

HAVRIX administered to infants born to anti-HAV positive mothers at ages 12 and 15 months

Group Type: EXPERIMENTAL

hepatitis A vaccine

Intervention Type: BIOLOGICAL

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.

HAVRIX ages 12, 15 mos; mom antibody-

HAVRIX administered to infants born to anti-HAV negative mothers at ages 12 and 15 months

Group Type: ACTIVE_COMPARATOR

hepatitis A vaccine

Intervention Type: BIOLOGICAL

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.

HAVRIX ages 15,21 mos; mom antibody +

HAVRIX administered to infants born to anti-HAV positive mothers at ages 15 and 21 months

Group Type: EXPERIMENTAL

hepatitis A vaccine

Intervention Type: BIOLOGICAL

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.

HAVRIX ages 15,21 mos; mom antibody -

HAVRIX administered to infants born to anti-HAV negative mothers at ages 15 and 21 months

Group Type: ACTIVE_COMPARATOR

hepatitis A vaccine

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

HAVRIX

Eligibility Criteria

Exclusion Criteria

-

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alaska Native Medical Center

OTHER

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian McMahon

Role: PRINCIPAL_INVESTIGATOR

Alaska Native Medical Center

Locations

Anchorage Neighborhood Health Center

Anchorage, Alaska, United States

Alaska Native Medical Center

Anchorage, Alaska, United States

Countries

United States

References

Bell BP, Negus S, Fiore AE, Plotnik J, Dhotre KB, Williams J, Shapiro CN, McMahon BJ. Immunogenicity of an inactivated hepatitis A vaccine in infants and young children. Pediatr Infect Dis J. 2007 Feb;26(2):116-22. doi: 10.1097/01.inf.0000253253.85640.cc.

Reference Type: RESULT

PMID: 17259872 (View on PubMed)

Other Identifiers

U50/CCU022279

Identifier Type: -

Identifier Source: secondary_id

CDC-NCID-1358

Identifier Type: -

Identifier Source: org_study_id