Immuno & Safety Study of GSK Biologicals' Thio or Preservative Free Hepatitis B Vaccine in Subjects Aged 11-15 Yrs

Long-term Study of Immune Response Persistence of GSK Biologicals' 2-dose Thiomersal-free Engerix™-B and 3-dose Preservative-free Engerix™-B Vaccines in Subjects Aged 11-15 Yrs

To evaluate the persistence of antibodies against hepatitis B at 30, 42, 54 and 66 months after the first dose of the hepatitis B primary vaccination course.

Subjects were aged 11 to 15 years at the time of the primary vaccination course.

At the time of enrollment in the present long-term follow-up study subjects were aged 13 to 18 years.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Biological: Engerix™-B (thiomersal-free) 20µg; Biological: placebo; Biological: 10 μg Engerix™-B (preservative-free)

Detailed Description

All subjects who participated in the primary study, in which they received either 2 or 3 doses of GSK Biologicals hepatitis B vaccine, and who consented to participate in the long-term follow-up at Month 42 were contacted by the investigators.

No additional subjects will be recruited during this long-term follow-up study and no vaccine will be administered.

• Study Type: Interventional
• Enrollment (Actual): 267
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia
      • GSK Investigational Site
• Belgium
  • Bruxelles, Belgium, 1200
    • GSK Investigational Site
  • Wilrijk, Belgium, 2610
    • GSK Investigational Site
• Ukraine
  • Kyiv, Ukraine, 03038
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects have participated in primary study HBV-280
• Written informed consent will be obtained from each subject and/ or parent or guardian of the subject before the blood-sampling visit of each year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2-Dose Engerix; subjects received 2 doses of adult (thiomersal-free) HBV formulation, one at 0 and 6 months, respectively and placebo (physiological saline) at 1 month.	Biological: Engerix™-B (thiomersal-free) 20µg; In the primary study: 2 deep intramuscular injections (Months 0, & 6); Biological: placebo; In the primary study: 1 deep intramuscular injection (month 1)
Active Comparator: 3-Dose Engerix; subjects received 3 doses of paediatric (preservative-free) HBV formulation one at 0, 1 and 6 months, respectively.	Biological: 10 μg Engerix™-B (preservative-free); In the primary study: 3 deep intramuscular injections (months 0, 1 & 6)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody.	A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.	At Month 7
Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody.	A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.	At Month 30, Month 42, Month 54 and Month 66
Antibody Titers Against Hepatitis-B Virus.	Antibody titers were summarized by Geometric Mean Concentrations (GMCs) with their 95% CIs.	At Month 30, Month 42, Month 54 and Month 66

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Titers Against Hepatitis-B Virus.	Antibody titers were summarized by Geometric Mean Concentrations (GMCs) with their 95% CIs.	At Months 1, 2, 6 and 7
Number of Subjects Seroprotected for Anti-HBs Antibody.	A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.	At Months 1, 2 and 6
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.	During the 4-day (Day 0-3) follow-up period after each vaccination and overall
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.	Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache, and fever. Any was defined as incidence of the specified symptoms regardless of intensity or relationship to study vaccine. Gastrointestinal symptoms included nausea, vomiting, diarrhea and abdominal pain. Grade 3 fever was defined as fever (axillary temperature) > 38.5°C. Grade 3 symptoms were defined as symptoms which prevented normal everyday activities. Related = general symptom assessed by the investigator as causally related to the vaccination.	During the 4-day (Day 0-3) follow-up period after each vaccination and overall
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE).	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	During the 31-day (Day 0-30) follow-up period after each vaccination and overall
Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that resulted in death, were 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.	During the entire study period (Month 0 to Month 66)
Number of Subjects With Serious Adverse Events (SAEs).	erious adverse events (SAEs) assessed include medical occurrences that resulted in death, were 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.	At Month 30, Month 42, Month 54 & Month 66

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Heron L, Selnikova O, Moiseieva A, Van Damme P, van der Wielen M, Levie K, Hoet B, Stoffel M. Immunogenicity, reactogenicity and safety of two-dose versus three-dose (standard care) hepatitis B immunisation of healthy adolescents aged 11-15 years: a randomised controlled trial. Vaccine. 2007 Apr 12;25(15):2817-22. doi: 10.1016/j.vaccine.2006.12.021. Epub 2006 Dec 29.
• Heron LG, Chant KG, Jalaludin BB. A novel hepatitis B vaccination regimen for adolescents: two doses 12 months apart. Vaccine. 2002 Oct 4;20(29-30):3472-6. doi: 10.1016/s0264-410x(02)00346-8.
• Van Damme P, Moiseeva A, Marichev I, Kervyn AD, Booy R, Kuriyakose S, Brockway A, Ng SP, Leyssen M, Jacquet JM. Five years follow-up following two or three doses of a hepatitis B vaccine in adolescents aged 11-15 years: a randomised controlled study. BMC Infect Dis. 2010 Dec 20;10:357. doi: 10.1186/1471-2334-10-357.

Helpful 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2004
• Primary Completion (Actual): January 10, 2008
• Study Completion (Actual): January 10, 2008

Study Registration Dates

• First Submitted: September 14, 2005
• First Submitted That Met QC Criteria: June 22, 2006
• First Posted (Estimate): June 23, 2006

Study Record Updates

• Last Update Posted (Actual): June 10, 2019
• Last Update Submitted That Met QC Criteria: February 12, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Persistence; Hepatitis B vaccine
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A
• Other Study ID Numbers: 101695 Ext. Mth30; 101696 (Other Identifier: GSK); 101697 (Other Identifier: GSK); 101698 (Other Identifier: GSK); 2015-001531-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 101695 Ext. Mth30
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 101695 Ext. Mth30
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 101695 Ext. Mth30
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 101695 Ext. Mth30
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register. The results of this study 101695 (Ext HBV-280 M30) are summarised with studies 103860/280 (HBV-280), 101696 (Ext HBV-280 M42), 101697 (Ext HBV-280 M54) and 101698
5. Dataset Specification
   Information identifier: 101695 Ext. Mth30
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register