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

NCT01000324 | Completed Phase 4 Results

• 1 other identifier: 112267
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis A; Hepatitis B

Keywords

Hepatitis A; Hepatitis B

Outcome Measures

Primary Outcomes (2)

• 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.

  At Years 16, 17, 18, 19 and 20.

• Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs)

  Concentrations were expressed as GMCs in mIU/mL.

  At Years 16, 17, 18, 19 and 20.

Secondary Outcomes (5)

• Number of Subjects With Immune Response to the Challenge Vaccine Antigen

  Before, 14 days and one month after the challenge dose at Year 19.

• Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration

  At Year 18, 14 days and 30 days post challenge dose (Year 19).

• Number of Subjects Reporting Unsolicited Adverse Events (AE)

  During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.

• Number of Subjects Reporting Serious Adverse Events (SAEs)

  During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.

• Number of Subjects Reporting Serious Adverse Events (SAEs)

  Up to Year 20.

Study Arms (1)

Twinrix Group

EXPERIMENTAL

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; Biological: Engerix-B; Biological: Havrix

Interventions

Blood sampling PROCEDURE

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).

Twinrix Group

Engerix-B BIOLOGICAL

Engerix-B will be administered to subjects who are not seroprotected against hepatitis B

Twinrix Group

Havrix BIOLOGICAL

Havrix will be administered to subjects who are seronegative for anti-HAV antibodies

Twinrix Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Wilrijk, 2610, Belgium

Location

Related Publications (1)

• 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.

  PMID: 32710245 DERIVED

Related Links

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

MeSH Terms

Conditions

Hepatitis A; Hepatitis B

Interventions

Blood Specimen Collection; Engerix-B; Hepatitis A Vaccines

Condition Hierarchy (Ancestors)

Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Limitations and Caveats

A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/ml). The table shows updated results following partial or complete retesting/reanalysis.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2009
• First Posted: October 23, 2009
• Study Start: November 6, 2009
• Primary Completion: July 25, 2014
• Study Completion: July 25, 2014
• Last Updated: September 4, 2018
• Results First Posted: January 13, 2011

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)