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Long-term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,1,6 Mth Schedule in Healthy Adults

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ClinicalTrials.gov Identifier: NCT00289770
Recruitment Status : Completed
First Posted : February 10, 2006
Results First Posted : February 23, 2011
Last Update Posted : August 17, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Hepatitis B
Hepatitis A
Intervention Biological: Twinrix™
Enrollment 50
Recruitment Details  
Pre-assignment Details Subjects who came back at a follow-up, did not necessarily come back at an earlier timepoint. Therefore amount of subjects who completed the previous timepoint does not always correspond with amount of subjects who entered follow-up. As Year 15 has enrolled the most subjects, baseline measures are given for Year 15, to be as complete as possible.
Arm/Group Title Twinrix Group
Hide Arm/Group Description Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Period Title: Year 11
Started 37
Completed 37
Not Completed 0
Period Title: Year 12
Started 40
Completed 40
Not Completed 0
Period Title: Year 13
Started 37
Completed 37
Not Completed 0
Period Title: Year 14
Started 43
Completed 43
Not Completed 0
Period Title: Year 15
Started 50
Completed 49
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Arm/Group Title Twinrix Group
Hide Arm/Group Description Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Overall Number of Baseline Participants 50
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 50 participants
34.4  (2.66)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Female
39
  78.0%
Male
11
  22.0%
1.Primary Outcome
Title Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value
Hide Description Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity.
Time Frame Years 11, 12, 13, 14 and 15
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the long-term (LT) According-To-Protocol (ATP) cohort for immunogenicity, which included subjects who returned at a particular blood sampling timepoint, were in the ATP immunogenicity cohort in the primary study and for whom serology results were available for that particular timepoint.
Arm/Group Title Twinrix Group
Hide Arm/Group Description:
Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Overall Number of Participants Analyzed 31
Measure Type: Count of Participants
Unit of Measure: Participants
Year 11 Number Analyzed 25 participants
25
 100.0%
Year 12 Number Analyzed 28 participants
28
 100.0%
Year 13 Number Analyzed 23 participants
23
 100.0%
Year 14 Number Analyzed 24 participants
24
 100.0%
Year 15 Number Analyzed 31 participants
31
 100.0%
2.Primary Outcome
Title Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values
Hide Description Cut-off values were defined 3.3 mIU/mL for the in-house anti-HBs assay and 6.2 mIU/mL for the ChemiLuminescence ImmunoAssay, which was also considered as seropositivity, and 10 mIU/mL.
Time Frame Years 11, 12, 13, 14 and 15
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the long-term (LT) According-To-Protocol (ATP) cohort for immunogenicity, which included subjects who returned at a particular blood sampling timepoint, were in the ATP immunogenicity cohort in the primary study and for whom serology results were available for that particular timepoint.
Arm/Group Title Twinrix Group
Hide Arm/Group Description:
Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Overall Number of Participants Analyzed 31
Measure Type: Count of Participants
Unit of Measure: Participants
Year 11 3.3 mIU/mL Number Analyzed 25 participants
23
  92.0%
Year 12 3.3 mIU/mL Number Analyzed 28 participants
25
  89.3%
Year 13 3.3 mIU/mL Number Analyzed 23 participants
20
  87.0%
Year 14 3.3 mIU/mL Number Analyzed 24 participants
21
  87.5%
Year 14 6.2 mIU/mL Number Analyzed 24 participants
21
  87.5%
Year 15 6.2 mIU/mL Number Analyzed 31 participants
28
  90.3%
Year 11 10 mIU/mL Number Analyzed 25 participants
23
  92.0%
Year 12 10 mIU/mL Number Analyzed 28 participants
25
  89.3%
Year 13 10 mIU/mL Number Analyzed 23 participants
20
  87.0%
Year 14 10 mIU/mL Number Analyzed 24 participants
21
  87.5%
Year 15 10 mIU/mL Number Analyzed 31 participants
28
  90.3%
3.Primary Outcome
Title Anti-HAV and Anti-HBs Antibody Concentrations
Hide Description

Concentrations are expressed as geometric mean concentrations (GMCs) in mIU/mL.

The laboratory assay was changed from Year 13 to Year 14 to in-house ELISA and at Year 15 to CLIA for anti-HBs GMCs.Thus for the sake of bridging, blood samples corresponding to Year 14 previously tested with ELISA were re-tested with CLIA (Year 14*).

Time Frame Years 11, 12, 13, 14 and 15
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the long-term (LT) According-To-Protocol (ATP) cohort for immunogenicity, which included subjects who returned at a particular blood sampling timepoint, were in the ATP immunogenicity cohort in the primary study and for whom serology results were available for that particular timepoint.
Arm/Group Title Twinrix Group
Hide Arm/Group Description:
Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Overall Number of Participants Analyzed 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: mIU/mL
Year 11 anti-HAV Number Analyzed 25 participants
680.3
(453.8 to 1019.9)
Year 12 anti-HAV Number Analyzed 28 participants
602.7
(420.8 to 863.2)
Year 13 anti-HAV Number Analyzed 23 participants
601.5
(408.7 to 885.4)
Year 14 anti-HAV Number Analyzed 24 participants
524.7
(368.7 to 746.5)
Year 15 anti-HAV Number Analyzed 31 participants
610.7
(443.1 to 841.6)
Year 11 anti-HBs Number Analyzed 25 participants
458.9
(257.4 to 817.8)
Year 12 anti-HBs Number Analyzed 28 participants
475.8
(284.4 to 795.9)
Year 13 anti-HBs Number Analyzed 23 participants
163.3
(99.7 to 267.3)
Year 14 anti-HBs Number Analyzed 24 participants
149.1
(94.8 to 234.5)
Year 14* anti-HBs Number Analyzed 24 participants
242.8
(127.0 to 464.3)
Year 15 anti-HBs Number Analyzed 31 participants
210.9
(121.5 to 366.2)
4.Primary Outcome
Title Anti-HBs Antibody Concentrations
Hide Description

Subjects who lost seroprotective concentrations for anti-HBs (< 10 mIU/mL) at any of the LT follow-up timepoints received an additional dose of Engerix after year 15.

Two subjects were eligible for this after Year 11.

3.29 in the table means a concentration of < 3.3 mIU/mL.

As the concentration was calculated per subject no mean concentration was calculated and also no measure of dispersion.

Time Frame at Year 11, pre-additional vaccine, after additional dose of Engerix
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available.
Arm/Group Title Twinrix Group
Hide Arm/Group Description:
Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: mIU/mL
subject 1 Year 11 3.29
subject 2 Year 11 3.29
subject 1 before additional dose 3.29
subject 2 before additional dose 14.5
subject 1 after additional dose 6548.1
subject 2 after additional dose 554.0
5.Primary Outcome
Title Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response
Hide Description

Anamnestic response was assessed in subjects receiving an additional vaccine dose of Engerix. Two subjects were found eligible at Year 11 for this additional vaccine dose.

Anamnestic response was defined as:

  • post-additional vaccination anti-HBs concentration >= 10 mIU/mL in subject seronegative before additional dose.
  • 4-fold increase post-additional dose compared to pre-additional vaccine time point.
Time Frame 30 days post additional dose of Engerix
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available.
Arm/Group Title Twinrix Group
Hide Arm/Group Description:
Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Overall Number of Participants Analyzed 2
Measure Type: Count of Participants
Unit of Measure: Participants
2
 100.0%
6.Primary Outcome
Title Number of Subjects With Solicited Local and General Symptoms Assessed
Hide Description Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, fever, gastrointestinal, headache.
Time Frame During the 4-day follow-up period after additional vaccination with Engerix
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available.
Arm/Group Title Twinrix Group
Hide Arm/Group Description:
Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Overall Number of Participants Analyzed 2
Measure Type: Count of Participants
Unit of Measure: Participants
Pain
0
   0.0%
Redness
0
   0.0%
Swelling
0
   0.0%
Fatigue
1
  50.0%
Fever
0
   0.0%
Gastrointestinal
1
  50.0%
Headache
0
   0.0%
7.Primary Outcome
Title Number of Subjects With Unsolicited Symptoms
Hide Description 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.
Time Frame During the 30-day follow-up period after additional Engerix vaccination
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available.
Arm/Group Title Twinrix Group
Hide Arm/Group Description:
Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Overall Number of Participants Analyzed 2
Measure Type: Count of Participants
Unit of Measure: Participants
1
  50.0%
8.Primary Outcome
Title Number of Subjects With Serious Adverse Events (SAEs)
Hide Description 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
Time Frame During the 30-day follow-up period after additional Engerix vaccination
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available.
Arm/Group Title Twinrix Group
Hide Arm/Group Description:
Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Overall Number of Participants Analyzed 2
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
9.Primary Outcome
Title Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy
Hide Description 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.
Time Frame up to Year 11, 12, 13, 14, 15
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the long-term (LT) Total Vaccinated Cohort, this included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling time-point and who had serology results for anti-HAV and anti-HBs available.
Arm/Group Title Twinrix Group
Hide Arm/Group Description:
Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Overall Number of Participants Analyzed 50
Measure Type: Count of Participants
Unit of Measure: Participants
Year 11 Number Analyzed 37 participants
0
   0.0%
Year 12 Number Analyzed 40 participants
0
   0.0%
Year 13 Number Analyzed 37 participants
0
   0.0%
Year 14 Number Analyzed 43 participants
0
   0.0%
Year 15 Number Analyzed 50 participants
0
   0.0%
Time Frame SAEs were collected up to Year 15. Other adverse events were collected within 4-days after additional vaccination (solicited) and 30-days after additional vaccination (unsolicited).
Adverse Event Reporting Description As the number of subjects differs for SAEs at the different timepoints the maximum number has been taken for the amount of subjects at risk.
 
Arm/Group Title Twinrix Group
Hide Arm/Group Description Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
All-Cause Mortality
Twinrix Group
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Twinrix Group
Affected / at Risk (%)
Total   0/50 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Twinrix Group
Affected / at Risk (%)
Total   2/2 (100.00%) 
Eye disorders   
Heaviness sensation above eyes *  1/2 (50.00%) 
General disorders   
Fatigue   1/2 (50.00%) 
Gastrointestinal   1/2 (50.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00289770     History of Changes
Other Study ID Numbers: 100551 (EXT Y11)
100552 (EXT Y12) ( Other Identifier: GSK )
100553 (EXT Y13) ( Other Identifier: GSK )
100554 (EXT Y14) ( Other Identifier: GSK )
100555 (EXT Y15) ( Other Identifier: GSK )
First Submitted: February 9, 2006
First Posted: February 10, 2006
Results First Submitted: November 30, 2010
Results First Posted: February 23, 2011
Last Update Posted: August 17, 2018