Evaluation of Immune Memory to Twinrix or Comparator by Challenge Dose Administration 4 Years After Primary Vaccination

Phase 4

Completed

Conditions: Hepatitis B
Hepatitis A

Interventions: Biological: Engerix-B
Biological: Twinrix
Biological: HBVAXPRO
Biological: Havrix
Biological: Vaqta

Registration Number: NCT00684671

Lead Sponsor: GlaxoSmithKline

Brief Summary: Only subjects who participated in the primary study will be invited to participate in the extension phase and the challenge dose phase of this study.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 506

Inclusion Criteria

Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
A male or female who completed the primary vaccination phase of the HAB-160 study (NCT 00603252).
Written informed consent obtained from the subject.
If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination.

Exclusion Criteria

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:

Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the challenge dose, or planned use during the study period.
History of any hepatitis A or hepatitis B vaccination or infection since the primary vaccination study.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
Acute disease at the time of enrolment.
Pregnant or lactating female.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Engerix + Havrix Group	Engerix-B	Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).
Engerix + Havrix Group	Havrix	Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).
Twinrix Group	Twinrix	Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).
HB VAX PRO + Vaqta Group	HBVAXPRO	Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
HB VAX PRO + Vaqta Group	Vaqta	Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies	One month after the challenge dose.	Anamnestic response was defined as : * for initially seronegative subjects, antibody concentration ≥ 10 Milli-International Units per Milliliter (mIU/mL), * for initially seropositive subjects: antibody concentration at ≥ 4 fold the pre-vaccination antibody concentration.
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies	One month after the challenge dose.	Anamnestic response was defined as: * for initially seronegative subjects, antibody concentration greater than or equal the cut-off \[≥ 15 Milli-International Units per Milliliter (mIU/mL)\], * for initially seropositive subjects with pre-vaccination antibody, concentration \< 100 mIU/mL: antibody concentration at least four times the pre-vaccination antibody concentration, * for initially seropositive subjects with pre-vaccination antibody concentration ≥ 100 mIU/mL: antibody concentration at least two times the pre-vaccination antibody concentration.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Serious Adverse Events (SAEs) Since the Last Study Visit of the HAB-160 (NCT00603252) Long-term Follow-up Study Considered by the Investigator to Have a Causal Relationship to Primary Vaccination	Since the last study visit of the primary study long-term follow-up study up to challenge dose administration (1 year)	A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B.
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations	Two weeks and one month after the challenge dose	Concentrations are given as geometric mean concentration (GMCs) expressed as mIU/mL.
Number of Subjects Reporting Solicited Symptoms	During the 4-day follow-up period after the challenge dose.	Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include fatigue, gastrointestinal symptoms, headache and temperature (above 37 degree Celsius).
Number of Subjects Reporting Unsolicited Symptoms	During the 31-day follow-up period after the challenge dose.	Unsolicited symptoms = any adverse event (AE) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Number of Subjects Reporting Serious Adverse Events (SAEs)	During one month following the administration of the challenge dose	A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B.