Long-Term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,6 Month Schedule

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00289744
• Collaborator: (none)
• Enrollment: 178
• Location: 1
• Arms: 3
• Actual Duration (Months): 61.9
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

The aim of this study is to evaluate the long-term persistence of hepatitis A and B antibodies at Years 6, 7, 8, 9 and 10 after subjects received their first two doses primary vaccination schedule of combined hepatitis A/hepatitis B vaccine.

This protocol posting deals with objectives & outcome measures of the extension phase at year 6 through to 10.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B; Hepatitis A	Biological: TWINRIX™ ADULT; Biological: Engerix TM	Phase 3

Detailed Description

To evaluate the long-term antibody persistence, volunteers will be bled at Years 6, 7, 8, 9 and 10 after the first vaccine dose of the primary vaccination course to determine their anti-HAV and anti-HBs antibody concentrations.

If a subject has become seronegative for anti-HAV antibodies or lost anti-HBs seroprotection concentrations at the long-term blood sampling time point (i.e. Years 6, 7, 8, 9 or 10), he/ she will be offered an additional vaccine dose.

Study Design

• Study Type: Interventional
• Actual Enrollment: 178 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Long-Term Follow-up Study to Evaluate the Immune Persistence of GSK Biologicals' Combined Hepatitis A / Hepatitis B Vaccine in Healthy Children
• Actual Study Start Date: Feb 16, 2004
• Actual Primary Completion Date: Apr 15, 2009
• Actual Study Completion Date: Apr 15, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Twinrix Group Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix in the primary study (208127/076)	Biological: TWINRIX™ ADULT; 2 doses IM injection in primary study
Experimental: Engerix-B Additional Dose (Adult) Subjects aged 16 years and above who received an additional dose of EngerixTM-B (adult dose).	Biological: Engerix TM; If a subject has become seronegative for anti-HAV antibodies or lost anti-HBs seroprotection concentrations at the long-term blood sampling time point (i.e. Years 6, 7, 8, 9 or 10), he/ she will be offered an additional vaccine dose.
Experimental: Engerix-B Additional Dose (Pediatric) Subjects under the age of 16 years who received an additional dose of EngerixTM-B (pediatric dose).	Biological: Engerix TM; If a subject has become seronegative for anti-HAV antibodies or lost anti-HBs seroprotection concentrations at the long-term blood sampling time point (i.e. Years 6, 7, 8, 9 or 10), he/ she will be offered an additional vaccine dose.

Outcome Measures

Primary Outcome Measures

1. Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration [Years 6, 7, 8, 9, and 10.]

2. Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration [At Year 6, 7, 8, 9 and 10]

3. Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration [Before and 1 month after the additional dose administration]

4. Number of Subjects With Immune Response to the Additional Dose of Engerix™-B [One month after the additional dose administration]

   Immune response was defined as: anti-hepatitis B surface antigen (anti-HBs) antibody concentration equal or above to 10 milli-international units per milliliter (mIU/mL) at 1 month post-challenge dose in subjects seronegative at the pre-challenge time-points at least a 4-fold increase in anti-HBs antibody concentrations at 1 month post-challenge dose in subjects seropositive at the pre-challenge time-points.

5. Number of Subjects Reporting Serious Adverse Events (SAEs) Assessed by the Investigator as Causally Related to Primary Vaccination, Study Procedures or Lack of Vaccine Efficacy [At Year 6, 7, 8, 9 and 10]

   Serious adverse events (SAEs) assessed include medical occurrences that result in death, is 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.

6. Number of Subjects Reporting Solicited Local and General Symptoms [During the 4-day follow-up period after additional dose]

   Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms and headache.

7. Number of Subjects Reporting Unsolicited Adverse Events [During the 30-day follow-up period after additional dose]

   Unsolicited adverse event (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.

8. Number of Subjects Reporting Serious Adverse Events (SAEs) [During the 30-day follow-up period after additional dose]

   Serious adverse events (SAEs) assessed include medical occurrences that result in death, is 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

Criteria

• Ages Eligible for Study: 7 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects participating in this study should have participated in the primary study with combined hepatitis A/ hepatitis B vaccine.

• Written informed consent will be obtained from each subject and/ or parent or guardian of the subject before the blood sampling visit of each year.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Wilrijk		Belgium	2610

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00289744
• Other Study ID Numbers: 100561 (Y6); 100562 (Year 7); 100563 (Year 8); 100564 (Year 9); 100565 (Year 10)
• First Posted: Feb 10, 2006
• Last Update Posted: Aug 20, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by GlaxoSmithKline: Hepatitis A; Hepatitis B; TWINRIX™ ADULT
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis

Study Results

Participant Flow

Recruitment Details	All subjects enrolled in the primary study (208127/076) were invited to come back for the long-term follow-up visits at Year 6 to 10. The enrollment in the protocol section reflects the amount of subjects who came back at year 6. At follow up timepoints less subjects came back.
Pre-assignment Detail	25 subjects lost seroprotective concentrations for anti-HBs antibodies at blood sampling time-points Years 6 to 10 and were offered an additional dose of Engerix™-B after Year 10 (additional dose phase). These subjects are presented in separate sub-groups for analysis purposes while as per study protocol, the single experimental group is Twinrix.

Arm/Group Title	Twinrix Group	Engerix-B Additional Dose (Adult)	Engerix-B Additional Dose (Pediatric)
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076)	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now 16 years and above and received an additional dose of EngerixTM-B (adult dose).	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now under the age of 16 years and received an additional dose of EngerixTM-B (pediatric dose).
Period Title: Year 6 Long-term Follow-up
STARTED	178	0	0
COMPLETED	178	0	0
NOT COMPLETED	0	0	0
Period Title: Year 6 Long-term Follow-up
STARTED	175	0	0
COMPLETED	175	0	0
NOT COMPLETED	0	0	0
Period Title: Year 6 Long-term Follow-up
STARTED	174	0	0
COMPLETED	174	0	0
NOT COMPLETED	0	0	0
Period Title: Year 6 Long-term Follow-up
STARTED	173	0	0
COMPLETED	173	0	0
NOT COMPLETED	0	0	0
Period Title: Year 6 Long-term Follow-up
STARTED	171	0	0
COMPLETED	171	0	0
NOT COMPLETED	0	0	0
Period Title: Year 6 Long-term Follow-up
STARTED	0	19	6
COMPLETED	0	19	6
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Twinrix Group
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076)
Overall Participants	178
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.1 (2.82)
Sex: Female, Male (Count of Participants)
Female	91 51.1%
Male	87 48.9%

Outcome Measures

1. Primary Outcome

Title	Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration
Time Frame	Years 6, 7, 8, 9, and 10.

Outcome Measure Data

Analysis Population Description

The analysis was performed on the long-term (LT) according to protocol (ATP) cohort for immunogenicity.

Arm/Group Title	Twinrix Group
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076)
Measure Participants	142
Year 6 (n=142)	692.3
Year 7 (n=136)	753.6
Year 8 (n=132)	544.4
Year 9 (n=121)	479.5
Year 10 (n=120)	601.6

2. Primary Outcome

Title	Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration
Time Frame	At Year 6, 7, 8, 9 and 10

Outcome Measure Data

Analysis Population Description

The analysis was performed on the long-term (LT) according to protocol (ATP) cohort for immunogenicity.

Arm/Group Title	Twinrix Group
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076)
Measure Participants	142
Year 6 (n= 142)	206.2
Year 7 (n= 136)	157.5
Year 8 (n= 132)	102.7
Year 9 (n = 121)	89.1
Year 10 (n= 120)	80.7

3. Primary Outcome

Title	Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration
Time Frame	Before and 1 month after the additional dose administration

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total vaccinated cohort for the additional dose.

Arm/Group Title	Engerix-B Additional Dose (Adult)	Engerix-B Additional Dose (Pediatric)
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now 16 years and above and received an additional dose of EngerixTM-B (adult dose).	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now under the age of 16 years and received an additional dose of EngerixTM-B (pediatric dose).
Measure Participants	19	6
Pre-vaccination	10.4	8.7
1 month after vaccination	1431.9	565.9

4. Primary Outcome

Title	Number of Subjects With Immune Response to the Additional Dose of Engerix™-B
Description	Immune response was defined as: anti-hepatitis B surface antigen (anti-HBs) antibody concentration equal or above to 10 milli-international units per milliliter (mIU/mL) at 1 month post-challenge dose in subjects seronegative at the pre-challenge time-points at least a 4-fold increase in anti-HBs antibody concentrations at 1 month post-challenge dose in subjects seropositive at the pre-challenge time-points.
Time Frame	One month after the additional dose administration

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total vaccinated cohort for the additional dose.

Arm/Group Title	Engerix-B Additional Dose (Adult)	Engerix-B Additional Dose (Pediatric)
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now 16 years and above and received an additional dose of EngerixTM-B (adult dose).	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now under the age of 16 years and received an additional dose of EngerixTM-B (pediatric dose).
Measure Participants	19	6
Count of Participants [Participants]	19 10.7%	6 NaN

5. Primary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs) Assessed by the Investigator as Causally Related to Primary Vaccination, Study Procedures or Lack of Vaccine Efficacy
Description	Serious adverse events (SAEs) assessed include medical occurrences that result in death, is 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.
Time Frame	At Year 6, 7, 8, 9 and 10

Outcome Measure Data

Analysis Population Description

The analysis was performed on the long-term (LT) total vaccinated cohort.

Arm/Group Title	Twinrix Group
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076)
Measure Participants	178
Year 6 (n= 178)	0 0%
Year 7 (n= 175)	0 0%
Year 8 (n= 174)	0 0%
Year 9 (n= 173)	0 0%
Year 10 (n= 171)	0 0%

6. Primary Outcome

Title	Number of Subjects Reporting Solicited Local and General Symptoms
Description	Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms and headache.
Time Frame	During the 4-day follow-up period after additional dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total vaccinated cohort for the additional dose.

Arm/Group Title	Engerix-B Additional Dose (Adult)	Engerix-B Additional Dose (Pediatric)
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now 16 years and above and received an additional dose of EngerixTM-B (adult dose).	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now under the age of 16 years and received an additional dose of EngerixTM-B (pediatric dose).
Measure Participants	19	6
Pain	6 3.4%	3 NaN
Redness	2 1.1%	1 NaN
Swelling	1 0.6%	0 NaN
Fatigue	2 1.1%	3 NaN
Fever	0 0%	1 NaN
Gastrointestinal symptoms	2 1.1%	1 NaN
Headache	3 1.7%	0 NaN

7. Primary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events
Description	Unsolicited adverse event (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.
Time Frame	During the 30-day follow-up period after additional dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total vaccinated cohort for the additional dose.

Arm/Group Title	Engerix-B Additional Dose (Adult)	Engerix-B Additional Dose (Pediatric)
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now 16 years and above and received an additional dose of EngerixTM-B (adult dose).	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now under the age of 16 years and received an additional dose of EngerixTM-B (pediatric dose).
Measure Participants	19	6
Count of Participants [Participants]	1 0.6%	1 NaN

8. Primary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs)
Description	Serious adverse events (SAEs) assessed include medical occurrences that result in death, is 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.
Time Frame	During the 30-day follow-up period after additional dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total vaccinated cohort for the additional dose.

Arm/Group Title	Engerix-B Additional Dose (Adult)	Engerix-B Additional Dose (Pediatric)
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now 16 years and above and received an additional dose of EngerixTM-B (adult dose).	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now under the age of 16 years and received an additional dose of EngerixTM-B (pediatric dose).
Measure Participants	19	6
Count of Participants [Participants]	0 0%	0 NaN

Adverse Events

Time Frame	SAEs: At each time-point of the long-term follow-up period & during the 30-day follow-up period after the additional dose. Other AEs: During the 4-day (solicited AEs) or the 30-day (unsolicited AEs) follow-up period after the additional dose.
Adverse Event Reporting Description	Safety results were only collected for those subjects receiving an additional vaccine dose (adult or pediatric)
Arm/Group Title	Engerix-B Additional Dose (Adult)		Twinrix Group		Engerix-B Additional Dose (Pediatric)
Arm/Group Description	Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now 16 years and above and received an additional dose of EngerixTM-B (adult dose).		Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076)		Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076). Subjects were now under the age of 16 years and received an additional dose of EngerixTM-B (pediatric dose).
All Cause Mortality
	Engerix-B Additional Dose (Adult)		Twinrix Group		Engerix-B Additional Dose (Pediatric)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Engerix-B Additional Dose (Adult)		Twinrix Group		Engerix-B Additional Dose (Pediatric)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/0 (NaN)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Engerix-B Additional Dose (Adult)		Twinrix Group		Engerix-B Additional Dose (Pediatric)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/19 (42.1%)		0/0 (NaN)		3/6 (50%)
Blood and lymphatic system disorders
Anaemia	0/19 (0%)		0/0 (NaN)		1/6 (16.7%)
General disorders
Pain	6/19 (31.6%)		0/0 (NaN)		3/6 (50%)
Redness	2/19 (10.5%)		0/0 (NaN)		1/6 (16.7%)
Swelling	1/19 (5.3%)		0/0 (NaN)		0/6 (0%)
Fatigue	2/19 (10.5%)		0/0 (NaN)		3/6 (50%)
Fever	0/19 (0%)		0/0 (NaN)		1/6 (16.7%)
Gastrointestinal symptoms	2/19 (10.5%)		0/0 (NaN)		1/6 (16.7%)
Headache	3/19 (15.8%)		0/0 (NaN)		0/6 (0%)
Nervous system disorders
Syncope	1/19 (5.3%)		0/0 (NaN)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.