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Long Term Follow-up Study at Years 2, 3, 4 and 5 Where 2 Dosing Schedules of the Combined Hepatitis A and B Vaccine Were Compared

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ClinicalTrials.gov Identifier: NCT00197184
Recruitment Status : Completed
First Posted : September 20, 2005
Results First Posted : June 4, 2009
Last Update Posted : August 20, 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
Interventions Biological: Twinrix™ Adult
Biological: Twinrix™ Junior
Enrollment 276
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation). Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Period Title: Overall Study
Started 139 137
Completed 139 137
Not Completed 0 0
Arm/Group Title Twinrix Adult Twinrix Junior Total
Hide Arm/Group Description Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation). Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation). Total of all reporting groups
Overall Number of Baseline Participants 139 137 276
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 139 participants 137 participants 276 participants
11.6  (2.97) 11.2  (3.11) 11.4  (3.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 139 participants 137 participants 276 participants
Female
59
  42.4%
64
  46.7%
123
  44.6%
Male
80
  57.6%
73
  53.3%
153
  55.4%
1.Primary Outcome
Title Anti-hepatitis A (HAV) Antibody Concentrations
Hide Description Geometric mean concentration for anti-HAV antibodies expressed as Milli-International Units per milliliter (mIU/mL)
Time Frame Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Long Term According to Protocol cohort for analysis of immunogenicity (LT ATP immunogenicity cohort) which included all subjects that complied with the protocol and for whom data concerning immunogenicity endpoint measures were available for the particular time point measured.
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description:
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Overall Number of Participants Analyzed 129 119
Geometric Mean (95% Confidence Interval)
Unit of Measure: mIU/mL
At year 2 Number Analyzed 107 participants 94 participants
1122.2
(937.7 to 1343.0)
1377.8
(1114.0 to 1704.2)
At year 3 Number Analyzed 129 participants 119 participants
998.6
(845.8 to 1178.9)
1347.1
(1145.1 to 1584.8)
At year 4 Number Analyzed 115 participants 105 participants
737.5
(623.6 to 872.3)
915.9
(774.0 to 1084.0)
At year 5 Number Analyzed 103 participants 101 participants
576.8
(473.6 to 702.5)
698.4
(585.1 to 833.7)
2.Primary Outcome
Title Anti-hepatitis B (HBs) Antibody Concentrations
Hide Description Geometric mean concentration for anti-HBs antibodies expressed as Milli-International Units per milliliter (mIU/mL).
Time Frame Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Long Term According to Protocol cohort for analysis of immunogenicity (LT ATP immunogenicity cohort) which included all subjects that complied with the protocol and for whom data concerning immunogenicity endpoint measures were available for the particular time point measured.
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description:
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Overall Number of Participants Analyzed 129 119
Geometric Mean (95% Confidence Interval)
Unit of Measure: mIU/mL
At year 2 Number Analyzed 107 participants 94 participants
479.9
(356.6 to 646.0)
830.6
(609.5 to 1131.9)
At year 3 Number Analyzed 129 participants 119 participants
325.1
(244.7 to 431.8)
695.1
(516.5 to 935.5)
At year 4 Number Analyzed 115 participants 105 participants
270.2
(201.0 to 363.3)
519.7
(378.5 to 713.6)
At year 5 Number Analyzed 102 participants 100 participants
150.2
(110.5 to 204.3)
283.7
(208.6 to 386.0)
3.Primary Outcome
Title Anti-HAV Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose.
Hide Description Any subjects becoming seronegative for anti-HAV antibodies (i.e. titres < 15 mIU/ml) at any long term time point, were to receive an additional vaccine dose administered between 6 to 12 months after Year 5 time point.
Time Frame Before and one month after additional vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
None of the subjects became seronegative for anti-HAV antibodies during the Year 2 to Year 5 long term follow-up. Hence none of the subjects received an additional Havrix dose.
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description:
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Primary Outcome
Title Anti-HBs Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose.
Hide Description Subjects losing seroprotective anti-HBs antibody titres (i.e. titres < 10 mIU/ml) at any long term time point, received an Engerix challenge dose. The table presents the geometric mean concentrations for anti-HBs antibodies, expressed as Milli-International Units per milliliter (mIU/mL).
Time Frame Before and One month after additional vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Total vaccinated cohort for the challenge dose, including all subjects who received an additional vaccine dose between 6 to 12 months after year 5.
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description:
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Overall Number of Participants Analyzed 11 5
Geometric Mean (95% Confidence Interval)
Unit of Measure: mIU/mL
Before vaccination Number Analyzed 6 participants 1 participants
4.9
(2.1 to 11.1)
2.4
(0.9 to 6.5)
Post vaccination Number Analyzed 11 participants 5 participants
521.3
(158.2 to 1718.1)
509.7
(173.5 to 1497.9)
5.Secondary Outcome
Title Number of Subjects Reporting 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

A serious adverse event (SAE) is any untoward medical occurrence that:

results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

Time Frame From last study visit of the primary study up to Year 5 long term follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Long term Total vaccinated cohort wich included all subjects who returned at a specified follow-up study
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description:
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Overall Number of Participants Analyzed 139 137
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited Local Symptoms
Hide Description

Solicited local symptoms assessed include pain, redness and swelling at the vaccine injection site.

Any= regardless of intensity grade; Grade 3 Pain= spontaneously painful

Time Frame during the 4-day follow-up period after additional vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Total vaccinated cohort for the challenge dose, including all subjects who received an additional vaccine dose between 6 to 12 months after year 5.
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description:
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Overall Number of Participants Analyzed 11 5
Measure Type: Count of Participants
Unit of Measure: Participants
Pain, any
6
  54.5%
0
   0.0%
Pain, grade 3
0
   0.0%
0
   0.0%
Redness, any
1
   9.1%
0
   0.0%
Redness, >20mm
0
   0.0%
0
   0.0%
Swelling, any
0
   0.0%
0
   0.0%
Swelling, >20mm
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Hide Description

Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms and headache.

Any= regardless of intensity grade or relationship to vaccination; grade 3= prevented normal activity; Related= considered by the investigator to be causally related to the vaccination

Time Frame During the 4-day follow-up period after additional vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Total vaccinated cohort for the challenge dose, including all subjects who received an additional vaccine dose between 6 to 12 months after year 5.
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description:
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Overall Number of Participants Analyzed 11 5
Measure Type: Count of Participants
Unit of Measure: Participants
Fatigue, any
3
  27.3%
0
   0.0%
Fatigue, grade 3
0
   0.0%
0
   0.0%
Fatigue, related
3
  27.3%
0
   0.0%
Fever (axillary), ≥37°C
0
   0.0%
0
   0.0%
Fever (axillary), >39.5°C
0
   0.0%
0
   0.0%
Fever (axillary), related
0
   0.0%
0
   0.0%
Gastrointestinal, any
2
  18.2%
0
   0.0%
Gastrointestinal, grade 3
0
   0.0%
0
   0.0%
Gastrointestinal, related
2
  18.2%
0
   0.0%
Headache, any
4
  36.4%
0
   0.0%
Headache, grade 3
0
   0.0%
0
   0.0%
Headache, related
4
  36.4%
0
   0.0%
8.Secondary Outcome
Title Number of Subjects Receiving an Additional Vaccine Dose and Reporting Unsolicited Adverse Events (AEs).
Hide Description An Adverse Event is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame During the 30-day follow-up period after additional vaccination.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Total vaccinated cohort for the challenge dose, including all subjects who received an additional vaccine dose between 6 to 12 months after year 5.
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description:
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Overall Number of Participants Analyzed 11 5
Measure Type: Count of Participants
Unit of Measure: Participants
2
  18.2%
0
   0.0%
9.Secondary Outcome
Title Number of Subjects Receiving an Additional Vaccine Dose and Reporting Any Serious Adverse Events
Hide Description

A serious adverse event (SAE) is any untoward medical occurrence that:

results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

Time Frame At least one month after additional vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Total vaccinated cohort for the challenge dose, including all subjects who received an additional vaccine dose between 6 to 12 months after year 5.
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description:
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Overall Number of Participants Analyzed 11 5
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
Time Frame Solicited symtoms: During the 4-day (Day 0-3) follow-up period after the additional vaccination. Unsolicited AEs: During the 31-day (Day 0-30) period after the additional vaccination; SAEs: During the entire study period
Adverse Event Reporting Description Solicited and unsolicited symptoms were collected on the Total vaccinated cohort for the challenge dose for subjects who received the additional vaccine dose after the Year 5; SAEs were collected on the Long term Total vaccinated cohort throughout the study period.
 
Arm/Group Title Twinrix Adult Twinrix Junior
Hide Arm/Group Description Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation). Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
All-Cause Mortality
Twinrix Adult Twinrix Junior
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Twinrix Adult Twinrix Junior
Affected / at Risk (%) Affected / at Risk (%)
Total   0/139 (0.00%)   0/137 (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 Adult Twinrix Junior
Affected / at Risk (%) Affected / at Risk (%)
Total   7/11 (63.64%)   0/5 (0.00%) 
General disorders     
Redness at the injection site   1/11 (9.09%)  0/5 (0.00%) 
Pain at the injection site   6/11 (54.55%)  0/5 (0.00%) 
Fatigue   3/11 (27.27%)  0/5 (0.00%) 
Gastrointestinal disorder   2/11 (18.18%)  0/5 (0.00%) 
Headache   4/11 (36.36%)  0/5 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia *  1/11 (9.09%)  0/5 (0.00%) 
Nervous system disorders     
Syncope vasovagal *  1/11 (9.09%)  0/5 (0.00%) 
Reproductive system and breast disorders     
Balanitis *  1/11 (9.09%)  0/5 (0.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00197184     History of Changes
Obsolete Identifiers: NCT00787449
Other Study ID Numbers: 208127/132 (EXT Y2)
208127/133 (EXT Y3) ( Other Identifier: GSK )
208127/134 (EXT Y4) ( Other Identifier: GSK )
208127/137 (EXT Y5) ( Other Identifier: GSK )
First Submitted: September 15, 2005
First Posted: September 20, 2005
Results First Submitted: February 20, 2009
Results First Posted: June 4, 2009
Last Update Posted: August 20, 2018