Immune Response of Healthy Subjects Who Received Neonatal Vaccination Course With Engerix™-B Vaccine.

Study to Evaluate the Immune Response of Healthy Subjects Who Received Neonatal Vaccination Course With GSK Biologicals' Engerix™-B Vaccine, Approximately 20 Years Ago.

This study will evaluate the immune response of healthy subjects who received neonatal vaccination course with GSK Biologicals' Engerix™-B vaccine, approximately 20 years ago. The presence of immune memory against hepatitis B surface antigen (HBsAg) in these subjects will be investigated by the administration of a challenge dose of hepatitis B vaccine and the comparison of their antibody concentration before and one month after vaccination.

This protocol posting deals with objectives & outcome measures of the booster phase. No new subjects will be recruited during this booster phase of the study.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 22 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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 neonatal primary vaccination course of Engerix™-B in the 103860/273 primary study approximately 20 years earlier.
• Anti-HBs antibody concentrations less than the specified value at the last available follow-up time-point.
• Written informed consent obtained from the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• If the subject is female, she must be of non-childbearing potential,or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the Engerix™-B challenge dose, or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressant or other immune-modifying drugs within six months prior to challenge dose administration.
• Planned administration/ administration of a vaccine not foreseen by the study protocol starting from 30 days before the challenge dose and ending 30 days after.
• Administration of a hepatitis B vaccine outside the context of this study between the follow-up time-point at which anti-HBs antibody concentrations was less than the specified value and the current challenge dose study visit.
• 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 product
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Acute disease at the time of enrolment.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Administration of immunoglobulins and/or any blood products within the three months preceding the challenge dose visit or planned administration during the study period.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Engerix(4-dose)+HepatitisB(HB) Immunoglobulin (Ig); Subjects who previously received HBV vaccine at 0, 1, 6 and 60 months (4 doses) and HBIg concomitantly at Month 0, and received a challenge dose of HBV vaccine after approximately 20 years (noted as Day 0) in the current study.	Biological: EngerixTM-B; Intramuscular injection, one dose.
Experimental: Engerix(3-dose)+HBIg; Subjects who previously received HBV vaccine at 0, 1, 6 months (3 doses) and HBIg concomitantly at Month 0, and received a challenge dose of HBV vaccine after approximately 20 years (noted as Day 0) in the current study.	Biological: EngerixTM-B; Intramuscular injection, one dose.
Experimental: Engerix(4-dose); Subjects who previously received HBV vaccine at 0, 1, 6 and 60 months (4 doses) and received a challenge dose of HBV vaccine after approximately 20 years (noted as Day 0) in the current study.	Biological: EngerixTM-B; Intramuscular injection, one dose.
Experimental: Engerix(3-dose); Subjects who previously received HBV vaccine at 0, 1, 6 months (3 doses) and received a challenge dose of HBV vaccine after approximately 20 years (noted as Day 0) in the current study.	Biological: EngerixTM-B; Intramuscular injection, one dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With an Anamnestic Response to a Challenge Dose of Hepatitis B Virus (HBV) Vaccine as Measured by Enzyme-Linked Immunosorbent Assay (ELISA).	Anamnestic response to the challenge dose is defined as: - At least (i.e. greater than or equal to) a 4-fold rise in post-challenge anti-HBsAg antibody concentrations in subjects seropositive at the last available follow-up time-point. -Post-challenge dose anti-HBsAg antibody concentrations >= 10 mIU/mL in subjects seronegative at the last available follow-up time-point.	One month after the hepatitis B vaccine challenge dose.
Number of Subjects With an Anamnestic Response to a Challenge Dose of Hepatitis B Virus (HBV) Vaccine as Measured by ChemiLuminescence ImmunoAssay (CLIA).	Anamnestic response to the challenge dose is defined as: - At least (i.e. greater than or equal to) a 4-fold rise in post-challenge anti-HBsAg antibody concentrations in subjects seropositive at the last available follow-up time-point. -Post-challenge dose anti-HBsAg antibody concentrations >= 10 mIU/mL in subjects seronegative at the last available follow-up time-point.	One month after the hepatitis B vaccine challenge dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Anti-Hepatitis B Surface (HBs) Antibody Concentrations Above Cut-off Values as Measured by ELISA.	Cut-off values assessed were as follows: ≥3.3 milli-international units/milliliter (mIU/mL), ≥10 mIU/mL, ≥100 mIU/mL	One month after the hepatitis B vaccine challenge dose.
Number of Subjects With Anti-Hepatitis B Surface (HBs) Antibody Concentrations Above Cut-off Values as Measured by CLIA.	Cut-off values assessed were as follows: ≥6.2 milli-international units/milliliter (mIU/mL), ≥10 mIU/mL, ≥100 mIU/mL	One month after the hepatitis B vaccine challenge dose.
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by ELISA.	Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL).	One month after the hepatitis B vaccine challenge dose.
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by CLIA.	Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL).	One month after the hepatitis B vaccine challenge dose.
Number of Subjects Experiencing Any, Grade 3 and Related to Vaccination 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. Grade 3 symptom is any event that prevented normal activities. Related symptom is an event that was considered by investigator as causally related to the study vaccination.	During the 31-day follow-up period after the hepatitis B vaccine challenge dose.
Number of Subjects That Experienced 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 entire study period after the challenge dose (1 month).

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Poovorawan Y, Chongsrisawat V, Theamboonlers A, Leroux-Roels G, Crasta PD, Hardt K. Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers. Hum Vaccin Immunother. 2012 Jul;8(7):896-904. doi: 10.4161/hv.19989. Epub 2012 Jul 1.

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: November 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: October 16, 2008
• First Submitted That Met QC Criteria: October 16, 2008
• First Posted (Estimate): October 17, 2008

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: September 27, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Hepatitis B; Engerix-B
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis
• Other Study ID Numbers: 110073

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. Statistical Analysis Plan
   Information identifier: 110073
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 110073
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 110073
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 110073
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 110073
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 110073
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register