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

• ClinicalTrials.gov Identifier: NCT00774995
• Recruitment Status: Completed
• First Posted: October 17, 2008
• Results First Posted: June 27, 2011
• Last Update Posted: November 2, 2016
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Study to Evaluate the Immune Response of Healthy Subjects Who Received Neonatal Vaccination Course With GSK Biologicals' Engerix™-B Vaccine, Approximately 20 Years Ago.
• Study Start Date: November 2008
• Actual Primary Completion Date: June 2010
• Actual Study Completion Date: June 2010

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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). [ Time Frame: One month after the hepatitis B vaccine challenge dose. ]
   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.
2. Number of Subjects With an Anamnestic Response to a Challenge Dose of Hepatitis B Virus (HBV) Vaccine as Measured by ChemiLuminescence ImmunoAssay (CLIA). [ Time Frame: One month after the hepatitis B vaccine challenge dose. ]
   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.

Secondary Outcome Measures :

1. Number of Subjects With Anti-Hepatitis B Surface (HBs) Antibody Concentrations Above Cut-off Values as Measured by ELISA. [ Time Frame: One month after the hepatitis B vaccine challenge dose. ]
   Cut-off values assessed were as follows: ≥3.3 milli-international units/milliliter (mIU/mL), ≥10 mIU/mL, ≥100 mIU/mL
2. Number of Subjects With Anti-Hepatitis B Surface (HBs) Antibody Concentrations Above Cut-off Values as Measured by CLIA. [ Time Frame: One month after the hepatitis B vaccine challenge dose. ]
   Cut-off values assessed were as follows: ≥6.2 milli-international units/milliliter (mIU/mL), ≥10 mIU/mL, ≥100 mIU/mL
3. Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by ELISA. [ Time Frame: One month after the hepatitis B vaccine challenge dose. ]
   Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL).
4. Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by CLIA. [ Time Frame: One month after the hepatitis B vaccine challenge dose. ]
   Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL).
5. Number of Subjects Experiencing Any, Grade 3 and Related to Vaccination Unsolicited Symptoms. [ Time Frame: During the 31-day follow-up period after the hepatitis B vaccine challenge dose. ]
   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.
6. Number of Subjects That Experienced Serious Adverse Events (SAEs) [ Time Frame: During the entire study period after the challenge dose (1 month). ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Thailand

GSK Investigational Site

Bangkok, Thailand, 10330

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

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 Data/Documents: Statistical Analysis Plan 

Identifier: 110073
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 110073
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: 110073
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 110073
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 110073
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 110073
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00774995
• Other Study ID Numbers: 110073
• First Posted: October 17, 2008
• Results First Posted: June 27, 2011
• Last Update Posted: November 2, 2016
• Last Verified: September 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.

Keywords provided by GlaxoSmithKline:

Engerix-B; Hepatitis B

Additional relevant MeSH terms:

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