Evaluation of Antibody Persistence & Immune Memory in Subjects Vaccinated During Adolescence With Twinrix™

NCT ID: NCT00875485

Last Updated: 2018-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-01
• Study Completion Date: 2014-07-01

Brief Summary

This study will evaluate the immune response against Hepatitis-A (HAV) and Hepatitis B surface (HBs) antigen in healthy subjects aged 12 to 15 years (at the time of primary vaccination), who received vaccination course with GSK Biologicals' Twinrix Adult and Twinrix Junior vaccine, approximately 10 years ago in the primary study. The subjects will be invited for blood sampling at 11, 12, 13, 14 and 15 years after primary vaccination to evaluate the persistence of immune response. For subjects detected with decreased immunity, the presence of immune memory against hepatitis A & B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine 6 to 12 months after the Year 15 follow-up time-point.

No new subjects will be recruited during this booster phase of the study.

Conditions

Hepatitis B; Hepatitis A

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Twinrix Adult Group

Subjects received 2 doses of Twinrix™ Adult intramuscularly according to a 0, 6 month schedule in the primary study

Group Type: EXPERIMENTAL

Blood sampling

Intervention Type: PROCEDURE

Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.

Additional challenge dose

Intervention Type: BIOLOGICAL

If a subject became seronegative for anti-HAV antibodies (\< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.

Twinrix Junior Group

Subjects received 3 doses of Twinrix™ Junior (= half dose Twinrix™ Adult) intramuscularly according to a 0, 1, 6 month schedule in the primary study

Group Type: EXPERIMENTAL

Blood sampling

Intervention Type: PROCEDURE

Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.

Additional challenge dose

Intervention Type: BIOLOGICAL

If a subject became seronegative for anti-HAV antibodies (\< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.

Interventions

Blood sampling

Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.

Intervention Type: PROCEDURE

Additional challenge dose

If a subject became seronegative for anti-HAV antibodies (\< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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 according to his/her group allocation in the primary study
• Written informed consent obtained from the subject.

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

• A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study.
• Subjects who participated in the long-term follow-up phase of the primary study and for whom the antibody concentrations were below specified value for anti-HAV antibodies and/ or for anti-HBs antibodies at the last available follow-up time-points.
• Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
• Written informed consent obtained from the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the challenge dose phase of this study.
• If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination.

Exclusion Criteria

The following criteria should be checked at each follow-up visit. If any apply at study entry, the subject must not be included at that long-term follow-up visit.

• Use of any investigational or non-registered product (drug or vaccine) since the last blood sampling visit.
• Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine since the primary vaccination course of the primary study.
• History of hepatitis A or hepatitis B infection.
• Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within 3 months prior to blood sampling.

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

• Use of any investigational or non-registered product (drug or vaccine) within 30 days before the administration of the challenge dose or planned use during the study period outside the context of the study.
• Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine between the primary vaccination course of the primary study and the challenge dose visit.
• History of hepatitis A or hepatitis B infection.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
• Acute disease at the time of.
• Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the challenge dose or planned administration before the final blood sampling point (one month after the challenge dose).
• Pregnant or lactating female.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Hradec Králové, , Czechia

Countries

Belgium; Czechia

References

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.

Reference Type: DERIVED

PMID: 32710245 (View on PubMed)

Beran J, Van Der Meeren O, Leyssen M, D'silva P. Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine. Vaccine. 2016 May 23;34(24):2686-91. doi: 10.1016/j.vaccine.2016.04.033. Epub 2016 Apr 20.

Reference Type: DERIVED

PMID: 27105563 (View on PubMed)

Study Documents

Document Type: Study Protocol

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

View Document

Document Type: Individual Participant Data Set

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

View Document

Document Type: Clinical Study Report

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

View Document

Document Type: Dataset Specification

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

View Document

Document Type: Informed Consent Form

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

View Document

Related Links

https://www.clinicalstudydatarequest.com

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Other Identifiers

110700

Identifier Type: OTHER

Identifier Source: secondary_id

110701

Identifier Type: OTHER

Identifier Source: secondary_id

110702

Identifier Type: OTHER

Identifier Source: secondary_id

110703

Identifier Type: OTHER

Identifier Source: secondary_id

110704

Identifier Type: OTHER

Identifier Source: secondary_id

110699

Identifier Type: -

Identifier Source: org_study_id