Back to resultsLong-term Persistence Study in Healthy Adults Previously Vaccinated With Twinrix Adult
Primary Purpose
Hepatitis A, Hepatitis B
Status
Completed
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Blood sampling
Engerix-B
Havrix
Sponsored by
About this trial
This is an interventional prevention trial for Hepatitis A focused on measuring Hepatitis A and hepatitis B
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.
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Twinrix Group
Arm Description
Subjects who received 2 doses of Twinrix (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Twinrix Group for data analyses during the first long-term follow-up NCT00289718 and this long-term follow-up. A challenge dose of the Havrix or Engerix-B vaccines can be administered in this study based on serology results at each time point.
Outcomes
Primary Outcome Measures
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)
Seropositivity for anti-HAV antibodies is defined as antibody concentrations >= 15 milliinternational units per milliliter (mIU/mL). Seropositivity for anti-HBs antibodies is defined as antibody concentrations >= 6.2 mIU/mL.
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs)
Concentrations were expressed as GMCs in mIU/mL.
Secondary Outcome Measures
Anti-HBs Concentrations After the Challenge Dose of Engerix-B
Concentration was given in mIU/mL.
Only 1 subject was eligible for the challenge dose of Engerix-B at the Year 16 time point. Therefore the values for this subject are given without a measure of dispersion.
Anti-HAV Concentrations After the Challenge Dose of Havrix
Concentration was given in mIU/mL. Only 2 subjects were eligible for the challenge dose of Havrix, one at Year 18 and another at Year 20 time point. Therefore the values for these subject are given without a measure of dispersion.
Number of Subjects With Anamnestic Response to the Challenge Dose of Engerix-B
At Year 16 only 1 subject was eligible for the challenge dose of Engerix-B.
Anti-HBs anamnestic response to the challenge dose was defined as:
Anti-HBs antibody concentrations >= 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time point.
At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time point.
Number of Subjects With Anamnestic Response to the Challenge Dose of Havrix
Anti-HAV anamnestic response to the challenge dose was defined as:
Anti-HAV antibody concentrations ≥ 15 mIU/mL at one month post-challenge dose, in subjects seronegative at the pre-challenge time point.
At least a 2-fold increase in anti-HAV antibody concentrations one month after the challenge dose, in subjects having anti-HAV antibody concentrations ≥ 100 mIU/mL at the pre-challenge time point.
Or at least a 4-fold increase in anti-HAV antibody concentrations one month after the challenge dose, in seropositive subjects having anti-HAV antibody concentrations < 100 mIU/mL at the pre-challenge time-point.
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
At Year 16, 1 subject was administered a challenge dose of Engerix-B and at Y18 and Y20, 2 subjects were administered a challenge dose of Havrix.
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Number of Subjects With Serious Adverse Events (SAEs)
Only 1 subject received a challenge dose at Year 16 of Engerix-B.
An SAE is any untoward medical occurrence that: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
Number of Subjects With Serious Adverse Events (SAEs)
One subject received a challenge dose of Havrix at Year 18 and another at Year 20.
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Number of Subjects Reporting SAEs Related to Study Participation or a Concurrent GSK Medication
An SAE is any untoward medical occurrence that: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01037114
Brief Title
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
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
January 27, 2010 (Actual)
Primary Completion Date
February 28, 2014 (Actual)
Study Completion Date
February 28, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis A, Hepatitis B
Keywords
Hepatitis A and hepatitis B
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Twinrix Group
Arm Type
Experimental
Arm Description
Subjects who received 2 doses of Twinrix (lot A, B or C) in the primary study.
As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Twinrix Group for data analyses during the first long-term follow-up NCT00289718 and this long-term follow-up.
A challenge dose of the Havrix or Engerix-B vaccines can be administered in this study based on serology results at each time point.
Intervention Type
Procedure
Intervention Name(s)
Blood sampling
Intervention Description
Blood sampling at Year 16, 17, 18, 19 and 20 and at the time of challenge dose administration and 14 days and one month after challenge dose administration (if challenge dose needed).
Intervention Type
Biological
Intervention Name(s)
Engerix-B
Intervention Description
Engerix-B will be administered to subjects who are not seroprotected against hepatitis B.
Intervention Type
Biological
Intervention Name(s)
Havrix
Intervention Description
Havrix will be administered to subjects who are seronegative for anti-HAV antibodies.
Primary Outcome Measure Information:
Title
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)
Description
Seropositivity for anti-HAV antibodies is defined as antibody concentrations >= 15 milliinternational units per milliliter (mIU/mL). Seropositivity for anti-HBs antibodies is defined as antibody concentrations >= 6.2 mIU/mL.
Time Frame
At Years 16, 17, 18, 19 and 20.
Title
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs)
Description
Concentrations were expressed as GMCs in mIU/mL.
Time Frame
At Years 16, 17, 18, 19 and 20.
Secondary Outcome Measure Information:
Title
Anti-HBs Concentrations After the Challenge Dose of Engerix-B
Description
Concentration was given in mIU/mL.
Only 1 subject was eligible for the challenge dose of Engerix-B at the Year 16 time point. Therefore the values for this subject are given without a measure of dispersion.
Time Frame
Before, 14 days and one month (30 days) after the challenge dose of Engerix-B.
Title
Anti-HAV Concentrations After the Challenge Dose of Havrix
Description
Concentration was given in mIU/mL. Only 2 subjects were eligible for the challenge dose of Havrix, one at Year 18 and another at Year 20 time point. Therefore the values for these subject are given without a measure of dispersion.
Time Frame
Before, 14 days and one month (30 days) after the challenge dose of Havrix.
Title
Number of Subjects With Anamnestic Response to the Challenge Dose of Engerix-B
Description
At Year 16 only 1 subject was eligible for the challenge dose of Engerix-B.
Anti-HBs anamnestic response to the challenge dose was defined as:
Anti-HBs antibody concentrations >= 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time point.
At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time point.
Time Frame
30 days after the challenge dose of Engerix-B.
Title
Number of Subjects With Anamnestic Response to the Challenge Dose of Havrix
Description
Anti-HAV anamnestic response to the challenge dose was defined as:
Anti-HAV antibody concentrations ≥ 15 mIU/mL at one month post-challenge dose, in subjects seronegative at the pre-challenge time point.
At least a 2-fold increase in anti-HAV antibody concentrations one month after the challenge dose, in subjects having anti-HAV antibody concentrations ≥ 100 mIU/mL at the pre-challenge time point.
Or at least a 4-fold increase in anti-HAV antibody concentrations one month after the challenge dose, in seropositive subjects having anti-HAV antibody concentrations < 100 mIU/mL at the pre-challenge time-point.
Time Frame
30 days after the challenge dose of Havrix.
Title
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Description
At Year 16, 1 subject was administered a challenge dose of Engerix-B and at Y18 and Y20, 2 subjects were administered a challenge dose of Havrix.
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame
31 days (Days 0-30) after the challenge dose of Engerix-B and Havrix.
Title
Number of Subjects With Serious Adverse Events (SAEs)
Description
Only 1 subject received a challenge dose at Year 16 of Engerix-B.
An SAE is any untoward medical occurrence that: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
Time Frame
During the 31-day (Days 0-30) follow-up period after the Engerix-B challenge dose.
Title
Number of Subjects With Serious Adverse Events (SAEs)
Description
One subject received a challenge dose of Havrix at Year 18 and another at Year 20.
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame
During the 31-day (Days 0-30) follow-up period after the Havrix challenge dose.
Title
Number of Subjects Reporting SAEs Related to Study Participation or a Concurrent GSK Medication
Description
An SAE is any untoward medical occurrence that: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
Time Frame
Up to Year 20.
10. Eligibility
Sex
All
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Citations:
PubMed Identifier
32710245
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.
Results Reference
derived
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112266
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112266
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112266
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112266
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112266
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112266
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112266
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Long-term Persistence Study in Healthy Adults Previously Vaccinated With Twinrix Adult
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