Antibody Persistence & Immune Memory in Healthy Adults Previously Vaccinated With Twinrix Adult

• ClinicalTrials.gov Identifier: NCT01000324
• Recruitment Status: Completed
• First Posted: October 23, 2009
• Results First Posted: January 13, 2011
• Last Update Posted: September 3, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis A; Hepatitis B	Procedure: Blood sampling; Biological: Engerix-B; Biological: Havrix	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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 Start Date: November 6, 2009
• Actual Primary Completion Date: July 25, 2014
• Actual Study Completion Date: July 25, 2014

Arms and Interventions

Arm

Intervention/treatment

Experimental: Twinrix Group; 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

Procedure: Blood sampling; 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).; Biological: Engerix-B; Engerix-B will be administered to subjects who are not seroprotected against hepatitis B; Biological: Havrix; Havrix will be administered to subjects who are seronegative for anti-HAV antibodies

Outcome Measures

Primary Outcome Measures :

1. 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) [ Time Frame: At Years 16, 17, 18, 19 and 20. ]
   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.
2. Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) [ Time Frame: At Years 16, 17, 18, 19 and 20. ]
   Concentrations were expressed as GMCs in mIU/mL.

Secondary Outcome Measures :

1. Number of Subjects With Immune Response to the Challenge Vaccine Antigen [ Time Frame: Before, 14 days and one month after the challenge dose at Year 19. ]
   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.
2. Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration [ Time Frame: At Year 18, 14 days and 30 days post challenge dose (Year 19). ]
   Concentrations are given as Geometric Mean Concentrations (GMCs) expressed as mIU/mL.
3. Number of Subjects Reporting Unsolicited Adverse Events (AE) [ Time Frame: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19. ]
   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.
4. Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19. ]
   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.
5. Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: Up to Year 20. ]
   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.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Belgium

GSK Investigational Site

Wilrijk, Belgium, 2610

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. 

Study Data/Documents: Individual Participant Data Set 

Identifier: 112267
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 112267
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: 112267
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 112267
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 112267
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 112267
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 112267
For additional information about this study please refer to the GSK Clinical Study Register

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01000324 History of Changes
• Other Study ID Numbers: 112267
• First Posted: October 23, 2009
• Results First Posted: January 13, 2011
• Last Update Posted: September 3, 2018
• Last Verified: January 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

Hepatitis A; Hepatitis B

Additional relevant MeSH terms:

Hepatitis A; Hepatitis B; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Hepadnaviridae Infections; DNA Virus Infections; Antibodies; Immunologic Factors; Physiological Effects of Drugs