Long-term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,1,6 Mth Schedule in Healthy Adults

NCT00289770 | Completed Phase 3 Results

• 5 other identifiers: 100551 (EXT Y11)100552 (EXT Y12)100553 (EXT Y13)100554 (EXT Y14)100555 (EXT Y15)
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the long-term persistence of hepatitis A and B antibodies at Years 11, 12, 13, 14 and 15 after subjects received their first dose of a 3 dose primary vaccination schedule of combined hepatitis A/hepatitis B vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. This protocol posting deals with objectives \& outcome measures of the extension phase at Year 11-15.

Conditions

Hepatitis B; Hepatitis A

Keywords

TWINRIX™ ADULT; Hepatitis A; Hepatitis B

Outcome Measures

Primary Outcomes (9)

• Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value

  Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity.

  Years 11, 12, 13, 14 and 15

• Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values

  Cut-off values were defined 3.3 mIU/mL for the in-house anti-HBs assay and 6.2 mIU/mL for the ChemiLuminescence ImmunoAssay, which was also considered as seropositivity, and 10 mIU/mL.

  Years 11, 12, 13, 14 and 15

• Anti-HAV and Anti-HBs Antibody Concentrations

  Concentrations are expressed as geometric mean concentrations (GMCs) in mIU/mL. The laboratory assay was changed from Year 13 to Year 14 to in-house ELISA and at Year 15 to CLIA for anti-HBs GMCs.Thus for the sake of bridging, blood samples corresponding to Year 14 previously tested with ELISA were re-tested with CLIA (Year 14\*).

  Years 11, 12, 13, 14 and 15

• Anti-HBs Antibody Concentrations

  Subjects who lost seroprotective concentrations for anti-HBs (\< 10 mIU/mL) at any of the LT follow-up timepoints received an additional dose of Engerix after year 15. Two subjects were eligible for this after Year 11. 3.29 in the table means a concentration of \< 3.3 mIU/mL. As the concentration was calculated per subject no mean concentration was calculated and also no measure of dispersion.

  at Year 11, pre-additional vaccine, after additional dose of Engerix

• Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response

  Anamnestic response was assessed in subjects receiving an additional vaccine dose of Engerix. Two subjects were found eligible at Year 11 for this additional vaccine dose. Anamnestic response was defined as: * post-additional vaccination anti-HBs concentration \>= 10 mIU/mL in subject seronegative before additional dose. * 4-fold increase post-additional dose compared to pre-additional vaccine time point.

  30 days post additional dose of Engerix

• Number of Subjects With Solicited Local and General Symptoms Assessed

  Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, fever, gastrointestinal, headache.

  During the 4-day follow-up period after additional vaccination with Engerix

• Number of Subjects With Unsolicited Symptoms

  Unsolicited AE covers any AE 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.

  During the 30-day follow-up period after additional Engerix vaccination

• Number of Subjects With Serious Adverse Events (SAEs)

  SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject

  During the 30-day follow-up period after additional Engerix vaccination

• Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy

  SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

  up to Year 11, 12, 13, 14, 15

Study Arms (3)

Group A

EXPERIMENTAL

Was vaccinated with Lot A in the primary study.

Biological: Twinrix™

Group B

EXPERIMENTAL

Was vaccinated with Lot B in the primary study.

Biological: Twinrix™

Group C

EXPERIMENTAL

Was vaccinated with Lot C in the primary study.

Biological: Twinrix™

Interventions

Twinrix™ BIOLOGICAL

Intramuscular injection, 3 doses

Group A; Group B; Group C

Eligibility Criteria

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

You may qualify if:

• Subjects who had consented to participate in the long-term follow-up studies at the previous long-term blood sampling time points
• Written informed consent will have been obtained from each subject. before the blood sampling visit of each year.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Wilrijk, 2610, Belgium

Location

Related Publications (3)

• Van Damme P, Leroux-Roels G, Crasta P, Messier M, Jacquet JM, Van Herck K. Antibody persistence and immune memory in adults, 15 years after a three-dose schedule of a combined hepatitis A and B vaccine. J Med Virol. 2012 Jan;84(1):11-7. doi: 10.1002/jmv.22264. Epub 2011 Nov 3.

  PMID: 22052690 BACKGROUND

• Van Damme P, Leroux-Roels G, Law B, Diaz-Mitoma F, Desombere I, Collard F, Tornieporth N, Van Herck K. Long-term persistence of antibodies induced by vaccination and safety follow-up, with the first combined vaccine against hepatitis A and B in children and adults. J Med Virol. 2001 Sep;65(1):6-13.

  PMID: 11505437 BACKGROUND

• Van Herck K, Leroux-Roels G, Van Damme P, Srinivasa K, Hoet B. Ten-year antibody persistence induced by hepatitis A and B vaccine (Twinrix) in adults. Travel Med Infect Dis. 2007 May;5(3):171-5. doi: 10.1016/j.tmaid.2006.07.003. Epub 2006 Sep 20.

  PMID: 17448944 BACKGROUND

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 B; Hepatitis A

Interventions

twinrix

Condition Hierarchy (Ancestors)

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

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 complete retesting and 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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2006
• First Posted: February 10, 2006
• Study Start: November 1, 2004
• Primary Completion: December 20, 2004
• Study Completion: December 20, 2004
• Last Updated: August 17, 2018
• Results First Posted: February 23, 2011

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)