Hepatitis APhase 4NCT00139113
Immunogenicity Study of an Inactivated Hepatitis A Vaccine in Infants and Young Children
A Phase 4 study testing hepatitis A vaccine in people with Hepatitis A, run by Centers for Disease Control and Prevention at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 25 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis A
- What is being tested?
- hepatitis A vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 248 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 1996to Jun 2001
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 25 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
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
-
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Anchorage Neighborhood Health Center
Anchorage, Alaska, 99501
Alaska Native Medical Center
Anchorage, Alaska, 99508
About this study
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.
Read the 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
- Being tested
- hepatitis A vaccine
- Keywords
- hepatitis A, hepatitis A vaccine
- Medical subject headings
- Hepatitis A, Hepatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hepatitis A vaccineBiological
Also called HAVRIX
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.
| Study group | Role | What they receive |
|---|---|---|
| HAVRIX 6 and 12 mos; mother antibody pos | Experimental | HAVRIX administered to infants born to anti-HAV positive mothers at ages 6 and 12 months Receives: Biological: hepatitis A vaccine |
| HAVRIX age 6, 12 mos; mom antibody neg | Active comparator | HAVRIX administered to infants born to anti-HAV negative mothers at ages 6 and 12 months Receives: Biological: hepatitis A vaccine |
| HAVRIX ages 12, 15 mos; mom antibody + | Experimental | HAVRIX administered to infants born to anti-HAV positive mothers at ages 12 and 15 months Receives: Biological: hepatitis A vaccine |
| HAVRIX ages 12, 15 mos; mom antibody- | Active comparator | HAVRIX administered to infants born to anti-HAV negative mothers at ages 12 and 15 months Receives: Biological: hepatitis A vaccine |
| HAVRIX ages 15,21 mos; mom antibody + | Experimental | HAVRIX administered to infants born to anti-HAV positive mothers at ages 15 and 21 months Receives: Biological: hepatitis A vaccine |
| HAVRIX ages 15,21 mos; mom antibody - | Active comparator | HAVRIX administered to infants born to anti-HAV negative mothers at ages 15 and 21 months Receives: Biological: hepatitis A vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
concentration of antibody to hepatitis A virus
Sera obtained at time of first hepatitis A vaccine dose (baseline) and 1, 7, and 12 months thereafter
Measured: baseline and 1, 7, and 12 months post vax
Secondary outcomes (2)
reported side effects and adverse events
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.
Measured: day of vaccination and 3 days thereafter
antibodies to routine childhood vaccinations
in a sample of study subjects from each group, blood drawn at age 13 months was tested for response to routine vaccinations.
Measured: age 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2005 (estimated)
- Study startSep 1996
- Primary completionJun 2001
- Study completionJun 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 248 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Collaborators
- Alaska Native Medical Center, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Brian McMahon, Principal investigator, Alaska Native Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00139113
- Sponsor's protocol ID
- CDC-NCID-1358
- Other IDs
- U50/CCU022279
- Status last verified
- Aug 2024
- First submitted
- 29 Aug 2005
- Last updated
- 20 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 17259872
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunogenicity Study of an Inactivated Hepatitis A Vaccine in Infants and Young Children
- ClinicalTrials.gov ID
- NCT00139113
- Acronym / sponsor ID
- CDC-NCID-1358
- Conditions
- Hepatitis A
- Keywords
- hepatitis A, hepatitis A vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 248 participants (actual)
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Collaborators
- Alaska Native Medical Center, GlaxoSmithKline
- Study start
- Sep 1996
- Primary completion
- Jun 2001 (actual)
- Study completion
- Jun 2001 (actual)
- First posted
- 31 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| HAVRIX 6 and 12 mos; mother antibody pos | Experimental | Biological: hepatitis A vaccineHAVRIX administered to infants born to anti-HAV positive mothers at ages 6 and 12 months |
| HAVRIX age 6, 12 mos; mom antibody neg | Active comparator | Biological: hepatitis A vaccineHAVRIX administered to infants born to anti-HAV negative mothers at ages 6 and 12 months |
| HAVRIX ages 12, 15 mos; mom antibody + | Experimental | Biological: hepatitis A vaccineHAVRIX administered to infants born to anti-HAV positive mothers at ages 12 and 15 months |
| HAVRIX ages 12, 15 mos; mom antibody- | Active comparator | Biological: hepatitis A vaccineHAVRIX administered to infants born to anti-HAV negative mothers at ages 12 and 15 months |
| HAVRIX ages 15,21 mos; mom antibody + | Experimental | Biological: hepatitis A vaccineHAVRIX administered to infants born to anti-HAV positive mothers at ages 15 and 21 months |
| HAVRIX ages 15,21 mos; mom antibody - | Active comparator | Biological: hepatitis A vaccineHAVRIX administered to infants born to anti-HAV negative mothers at ages 15 and 21 months |
Who may qualify
- Ages
- 6 months to 25 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hepatitis A vaccineAlso: HAVRIX2 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. | Biological | HAVRIX 6 and 12 mos; mother antibody pos, HAVRIX age 6, 12 mos; mom antibody neg, HAVRIX ages 12, 15 mos; mom antibody +, HAVRIX ages 12, 15 mos; mom antibody-, HAVRIX ages 15,21 mos; mom antibody +, HAVRIX ages 15,21 mos; mom antibody - |
Primary outcome
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
2 secondary outcomes
reported side effects and adverse events
Time frame: day of vaccination and 3 days thereafter
antibodies to routine childhood vaccinations
Time frame: age 13 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2024.
- Results publication: PubMed 17259872Bell 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian McMahon principal investigator
Alaska Native Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing hepatitis A vaccine in people with Hepatitis A, run by Centers for Disease Control and Prevention at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
concentration of antibody to hepatitis A virus (time frame: baseline and 1, 7, and 12 months post vax). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00139113, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2024; AzTrials last refreshed its copy on 7 Nov 2026.