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

• ClinicalTrials.gov Identifier: NCT02901951
• Recruitment Status: Completed
• First Posted: September 15, 2016
• Results First Posted: August 3, 2018
• Last Update Posted: January 2, 2020
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hepatitis B Vaccine	Biological: Engerix-B	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 106 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Long-term Persistence of Immunity to Hepatitis B in Adults Vaccinated 20 to 30 Years Ago With Engerix-B
• Actual Study Start Date: October 11, 2016
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose [ Time Frame: 7 days after the challenge dose (Day 7) ]
   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.
2. Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose [ Time Frame: 30 days after the challenge dose (Day 30) ]
   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.

Secondary Outcome Measures :

1. Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values [ Time Frame: 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) ]
   Percentage of subjects with anti-HBs antibody concentrations ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL.
2. Anti-HBs Antibody Concentrations [ Time Frame: 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) ]
   Anti-HBs antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.
3. Number of Subjects With Any Solicited Local Adverse Events (AEs) [ Time Frame: During the 4-day (Days 0-3) follow-up period after the challenge dose ]
   Assessed solicited local symptoms were injection site pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.
4. Number of Subjects With Any Solicited General AEs [ Time Frame: During the 4-day (Days 0-3) follow-up period after the challenge dose ]
   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.
5. Number of Subjects With Any Unsolicited AEs [ Time Frame: During the 31-day (Days 0-30) follow-up period after the challenge dose ]
   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.
6. Number of Subjects With Any Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (Day 0 to Day 30) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Belgium

GSK Investigational Site

Ghent, Belgium, 9000

GSK Investigational Site

Wilrijk, Belgium, 2610

Canada, Quebec

GSK Investigational Site

Québec City, Quebec, Canada, G1E 7G9

GSK Investigational Site

Sherbrooke, Quebec, Canada, J1H 2G2

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:

Study Protocol  [PDF] February 2, 2016

Statistical Analysis Plan  [PDF] October 12, 2017

More Information

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.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02901951
• Other Study ID Numbers: 116811; 2015-004099-31 ( EudraCT Number )
• First Posted: September 15, 2016
• Results First Posted: August 3, 2018
• Last Update Posted: January 2, 2020
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• 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.
• URL: https://www.clinicalstudydatarequest.com/SearchAllPostings.aspx?searchparam=116811

Keywords provided by GlaxoSmithKline:

Hepatitis B surface antigen antibody; adult subjects; Hepatitis B; HBV

Additional relevant MeSH terms:

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