Clinical trial NCT00139113: Immunogenicity Study of an Inactivated Hepatitis A Vaccine in Infants and Young Children
Official title: Immunogenicity Study of an Inactivated Hepatitis A Vaccine in Infants and Young Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis A
Keywords: hepatitis A
hepatitis A vaccine
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: Alaska Native Medical Center
name: GlaxoSmithKline
First posted: 2005-08-31
Enrollment: 248
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility 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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Primary outcomes:
measure: concentration of antibody to hepatitis A virus
timeFrame: baseline and 1, 7, and 12 months post vax
Secondary outcomes:
measure: reported side effects and adverse events
timeFrame: day of vaccination and 3 days thereafter
measure: antibodies to routine childhood vaccinations
timeFrame: age 13 months
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Anchorage Neighborhood Health Center
state: Alaska
city: Anchorage
country: United States
facility: Alaska Native Medical Center
state: Alaska
Study officials:
affiliation: Alaska Native Medical Center
name: Brian McMahon
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.