Back to resultsAntibody Persistence & Immune Memory 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, 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 Hepatitis A and B vaccine (HAB), HAB-028 (208127/021).
- 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 HAB-028 (208127/021).
- Written informed consent obtained from the subject.
- Subjects who participated in the long-term follow-up (LTFU) phase of the HAB-028 (208127/021) 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 HAB-028 (208127/021).
- History of hepatitis A or hepatitis B infection since the primary study HAB-028 (208127/021).
- 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
Pooled group of subjects from groups who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
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
Number of Subjects With Immune Response to the Challenge Vaccine Antigen
None of the subjects received a challenge dose at Years 16, 17, 18 and 20 while, one subject received the challenge dose at Year 19.
Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration
Concentrations are given as Geometric Mean Concentrations (GMCs) expressed as mIU/mL.
Number of Subjects Reporting Unsolicited Adverse Events (AE)
An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Number of Subjects Reporting Serious Adverse Events (SAEs)
A serious adverse event was any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Number of Subjects Reporting Serious Adverse Events (SAEs)
A serious adverse event is any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, or was a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01000324
Brief Title
Antibody Persistence & Immune Memory 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-028 (208127/021) 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
November 6, 2009 (undefined)
Primary Completion Date
July 25, 2014 (Actual)
Study Completion Date
July 25, 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 GlaxoSmithKline (GSK) Biologicals' Twinrix Adult. The subjects will be invited for blood sampling 16, 17, 18, 19 and 20 years after 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, 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
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Twinrix Group
Arm Type
Experimental
Arm Description
Pooled group of subjects from groups who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
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
Number of Subjects With Immune Response to the Challenge Vaccine Antigen
Description
None of the subjects received a challenge dose at Years 16, 17, 18 and 20 while, one subject received the challenge dose at Year 19.
Time Frame
Before, 14 days and one month after the challenge dose at Year 19.
Title
Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration
Description
Concentrations are given as Geometric Mean Concentrations (GMCs) expressed as mIU/mL.
Time Frame
At Year 18, 14 days and 30 days post challenge dose (Year 19).
Title
Number of Subjects Reporting Unsolicited Adverse Events (AE)
Description
An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Time Frame
During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.
Title
Number of Subjects Reporting Serious Adverse Events (SAEs)
Description
A serious adverse event was any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Time Frame
During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.
Title
Number of Subjects Reporting Serious Adverse Events (SAEs)
Description
A serious adverse event is any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, or was a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
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 Hepatitis A and B vaccine (HAB), HAB-028 (208127/021).
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 HAB-028 (208127/021).
Written informed consent obtained from the subject.
Subjects who participated in the long-term follow-up (LTFU) phase of the HAB-028 (208127/021) 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 HAB-028 (208127/021).
History of hepatitis A or hepatitis B infection since the primary study HAB-028 (208127/021).
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
Wilrijk
ZIP/Postal Code
2610
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
112267
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
112267
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
112267
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
112267
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
112267
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
112267
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
112267
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Antibody Persistence & Immune Memory in Healthy Adults Previously Vaccinated With Twinrix Adult
We'll reach out to this number within 24 hrs