Long-term Persistence of Immunity to Hepatitis B in Adults Vaccinated With GlaxoSmithKline (GSK) Biologicals' Hepatitis B Vaccine (HBV), Engerix-B

Long-term Persistence of Immunity to Hepatitis B in Adults Vaccinated 20 to 30 Years Ago With Engerix-B

The purpose of this study is to assess the long-term protection against HBV infection in adult subjects, aged 18-40 years vaccinated with three or four doses of Engerix-B 20 to 30 years ago

Study Overview

• Status: Completed
• Conditions: Hepatitis B Vaccine
• Intervention / Treatment: Biological: Engerix-B

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • GSK Investigational Site
  • Wilrijk, Belgium, 2610
    • GSK Investigational Site
• Canada
  • Quebec
    • Québec City, Quebec, Canada, G1E 7G9
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 2G2
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• A male or female between and including 40 and 60 years of age (from and including the 40th birthday up to, but excluding, the 61st birthday) at the time of the vaccination.
• Written informed consent obtained from the subject.

• Documented evidence of previous vaccination with three or four consecutive doses of Engerix-B administered in adulthood (i.e. at least 18 years of age) with

  • the last dose received 4 to 12 months after the previous one,
  • no subsequent booster dose ever received later, and
  • the last dose received 20 to 30 years before enrolment.

• Female subjects of non-childbearing potential may be enrolled in the study.

  • Non-childbearing potential is defined as pre-menarche, hysterectomy, ovariectomy or post-menopause.

• 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 during the entire treatment period and for one month after vaccination.

Exclusion Criteria:

• Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the dose of study vaccine, or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs at any time during the study period.
• Previous hepatitis B booster vaccination since completion of the primary vaccination series with three or four doses of Engerix-B.
• Planned administration of a vaccine not foreseen by the study protocol within 30 days preceding the dose of study vaccine, or planned administration during the study period, with the exception of seasonal influenza vaccine.
• Any medical condition that in the judgment of the investigator places the subject at undue risk by participating in the study.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
• History of hepatitis B disease or episode of jaundice with unknown etiology.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Major congenital defects or serious chronic illness (including insulin-dependent diabetes).

• Acute disease and/or fever at the time of enrolment.

  • Fever is defined as temperature ≥37.5°C for oral, axillary or tympanic route, or 38.0°C on rectal route.
  • Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the dose of study vaccine, or planned administration during the study period.
• Drug and/ or alcohol abuse within the last 5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HBV Group; Subjects aged 40 to 60 years old who received 3 or 4 doses of Engerix-B (HBV vaccine) 20 to 30 years ago and were administered with a single challenge dose of HBV vaccine in this study at Day 0 (Visit 1).	Biological: Engerix-B; Intramuscular administration of single challenge dose of Engerix-B vaccine in the deltoid region of the non-dominant arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose	Anamnestic response to the challenge dose was defined as: At least (i.e. greater than or equal to [≥]) 4-fold rise in one month post-vaccination anti-hepatitis B surface antigen (anti-HBs) antibody concentrations in previously seropositive subjects (Subjects with anti-HBs antibody concentration ≥ 6.2 milli International Unit/Milliliter (mIU/mL) at the pre-challenge dose time point); In previously seronegative subjects (Subjects with anti-HBs antibody concentration < 6.2 mIU/mL at the pre-challenge dose time point), anti-HBs antibody concentrations ≥10 mIU/mL at one month post-challenge dose time-point.	7 days after the challenge dose (Day 7)
Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose	Anamnestic response to the challenge dose was defined as: At least (i.e. ≥ 4-fold rise in one month post-vaccination anti-HBs antibody concentrations in previously seropositive subjects (Subjects with anti-HBs antibody concentration ≥ 6.2 mIU/mL at the pre-challenge dose time point); In previously seronegative subjects (Subjects with anti-HBs antibody concentration < 6.2 mIU/mL at the pre-challenge dose time point), anti-HBs antibody concentrations ≥10 mIU/mL at one month post-challenge dose time-point.	30 days after the challenge dose (Day 30)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values	Percentage of subjects with anti-HBs antibody concentrations ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL.	At the pre-challenge dose time-point (Day 0), at 7 days post-challenge time-point (Day 7) and at 30 days post-challenge time-point (Day 30)
Anti-HBs Antibody Concentrations	Anti-HBs antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.	At the pre-challenge dose time-point (Day 0), at 7 days post-challenge dose time-point (Day 7) and at 30 days post-challenge dose time-point (Day 30)
Number of Subjects With Any Solicited Local Adverse Events (AEs)	Assessed solicited local symptoms were injection site pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.	During the 4-day (Days 0-3) follow-up period after the challenge dose
Number of Subjects With Any Solicited General AEs	Assessed solicited general symptoms were fatigue, fever (defined as axillary temperature ≥ 37.5 degrees Celsius [°C]) , gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain) and headache. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.	During the 4-day (Days 0-3) follow-up period after the challenge dose
Number of Subjects With Any Unsolicited AEs	An 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. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.	During the 31-day (Days 0-30) follow-up period after the challenge dose
Number of Subjects With Any Serious Adverse Events (SAEs)	SAEs assessed included any untoward medical occurrences that resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or congenital anomaly/birth defect in the offspring of a study subject. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.	During the entire study period (Day 0 to Day 30)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Van Damme P, Dionne M, Leroux-Roels G, Van Der Meeren O, Di Paolo E, Salaun B, Surya Kiran P, Folschweiller N. Persistence of HBsAg-specific antibodies and immune memory two to three decades after hepatitis B vaccination in adults. J Viral Hepat. 2019 Sep;26(9):1066-1075. doi: 10.1111/jvh.13125. Epub 2019 Jun 2.

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2016
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: September 10, 2016
• First Submitted That Met QC Criteria: September 10, 2016
• First Posted (Estimate): September 15, 2016

Study Record Updates

• Last Update Posted (Actual): January 2, 2020
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Hepatitis B; HBV; Hepatitis B surface antigen antibody; adult subjects
• 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: 116811; 2015-004099-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)