Clinical trial NCT01037114: Long-term Persistence Study in Healthy Adults Previously Vaccinated With Twinrix Adult
Official title: An Open Single Centre Study to Evaluate the Long-term Antibody Persistence and Immune Memory Between 16 and 20 Years After the Primary Study HAB-032 (208127/022) in Which Healthy Adults Were Vaccinated With Twinrix Adult Following a Three-dose Schedule.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis A
Hepatitis B
Keywords: Hepatitis A and hepatitis B
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-12-21
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This study will evaluate the persistence of the immune response to HAV (hepatitis A virus) antigens and HBs (hepatitis B surface) antigens in healthy adults previously vaccinated with Twinrix Adult in the primary study, HAB-032 (208127/022). The subjects will be invited for blood sampling 16, 17, 18, 19 and 20 years after the primary vaccination to evaluate the antibody persistence. For subjects in whom low circulating antibodies are detected, the presence of immune memory against hepatitis A \& B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine (Havrix and/or Engerix-B) at the next planned visit.

No new subjects will be recruited during this study.


Eligibility criteria: Inclusion Criteria:

All subjects must satisfy the following criteria at entry into each of the long-term follow-up visits:

* Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
* A male or female who received the complete primary vaccination course in the primary study 208127/022.
* Written informed consent obtained from the subject.

All subjects must satisfy the following criteria at entry into the challenge dose phase:

* Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
* A male or female who received the complete primary vaccination course in the primary study 208127/022.
* Written informed consent obtained from the subject.
* Subjects who participated in the LTFU phase of the 208127/022 study and for whom the antibody concentrations were below the cut-off at the last available follow-up time-point.
* Female subjects of non-childbearing potential may be enrolled in the study.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:
* has practiced adequate contraception for 30 days prior to vaccination, and
* has a negative pregnancy test on the day of vaccination, and
* has agreed to continue adequate contraception for two months after the administration of the challenge dose.

Exclusion Criteria:

The following criteria should be checked before entry into each of the long-term follow-up visits. If any exclusion criterion applies, the subject must not be included in the study:

* Use of any investigational or non-registered product within 30 days prior to blood sampling.
* Administration of a hepatitis A, hepatitis B or combined hepatitis A and B vaccine outside the study procedures, since the primary study 208127/022.
* History of hepatitis A or hepatitis B infection since the primary study 208127/022.
* Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within three months prior to blood sampling.

The following criteria should be checked before the challenge dose is administered. If any apply, the subject must not be included in the challenge dose phase:

* Use of any investigational or non-registered product within 30 days prior to study start or planned use during the study.
* Administration of a hepatitis A, hepatitis B or combined hepatitis A and B vaccine between the last LTFU visit and the challenge dose visit.
* History of hepatitis A or hepatitis B infection between the last LTFU visit and the challenge dose visit.
* History of anaphylactic reactions following the administration of vaccines.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
* Acute disease and/or fever at the time of enrolment.
* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.

Primary outcomes:
measure: Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL)
timeFrame: At Years 16, 17, 18, 19 and 20.
measure: Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs)
timeFrame: At Years 16, 17, 18, 19 and 20.
Secondary outcomes:
measure: Anti-HBs Concentrations After the Challenge Dose of Engerix-B
timeFrame: Before, 14 days and one month (30 days) after the challenge dose of Engerix-B.
measure: Anti-HAV Concentrations After the Challenge Dose of Havrix
timeFrame: Before, 14 days and one month (30 days) after the challenge dose of Havrix.
measure: Number of Subjects With Anamnestic Response to the Challenge Dose of Engerix-B
timeFrame: 30 days after the challenge dose of Engerix-B.
measure: Number of Subjects With Anamnestic Response to the Challenge Dose of Havrix
timeFrame: 30 days after the challenge dose of Havrix.
measure: Number of Subjects Reporting Unsolicited Adverse Events (AEs)
timeFrame: 31 days (Days 0-30) after the challenge dose of Engerix-B and Havrix.
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the 31-day (Days 0-30) follow-up period after the Engerix-B challenge dose.
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the 31-day (Days 0-30) follow-up period after the Havrix challenge dose.
measure: Number of Subjects Reporting SAEs Related to Study Participation or a Concurrent GSK Medication
timeFrame: Up to Year 20.
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Agrawal A, Kolhapure S, Andani A, Ota MOC, Badur S, Karkada N, Mitra M. Long-Term Persistence of Antibody Response with Two Doses of Inactivated Hepatitis A Vaccine in Children. Infect Dis Ther. 2020 Dec;9(4):785-796. doi: 10.1007/s40121-020-00311-8. Epub 2020 Jul 24.