Trial Outcomes & Findings for 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 (NCT NCT00197184)
NCT ID: NCT00197184
Last Updated: 2018-08-20
Results Overview
Geometric mean concentration for anti-HAV antibodies expressed as Milli-International Units per milliliter (mIU/mL)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
276 participants
Primary outcome timeframe
Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60)
Results posted on
2018-08-20
Participant Flow
Participant milestones
| Measure |
Twinrix Adult
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
|---|---|---|
|
Overall Study
STARTED
|
139
|
137
|
|
Overall Study
COMPLETED
|
139
|
137
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Twinrix Adult
n=139 Participants
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
n=137 Participants
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
Total
n=276 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
11.6 years
STANDARD_DEVIATION 2.97 • n=5 Participants
|
11.2 years
STANDARD_DEVIATION 3.11 • n=7 Participants
|
11.4 years
STANDARD_DEVIATION 3.04 • n=5 Participants
|
|
Sex: Female, Male
Female
|
59 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
123 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
80 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
153 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60)Population: 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.
Geometric mean concentration for anti-HAV antibodies expressed as Milli-International Units per milliliter (mIU/mL)
Outcome measures
| Measure |
Twinrix Adult
n=129 Participants
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
n=119 Participants
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
|---|---|---|
|
Anti-hepatitis A (HAV) Antibody Concentrations
At year 2
|
1122.2 mIU/mL
Interval 937.7 to 1343.0
|
1377.8 mIU/mL
Interval 1114.0 to 1704.2
|
|
Anti-hepatitis A (HAV) Antibody Concentrations
At year 3
|
998.6 mIU/mL
Interval 845.8 to 1178.9
|
1347.1 mIU/mL
Interval 1145.1 to 1584.8
|
|
Anti-hepatitis A (HAV) Antibody Concentrations
At year 4
|
737.5 mIU/mL
Interval 623.6 to 872.3
|
915.9 mIU/mL
Interval 774.0 to 1084.0
|
|
Anti-hepatitis A (HAV) Antibody Concentrations
At year 5
|
576.8 mIU/mL
Interval 473.6 to 702.5
|
698.4 mIU/mL
Interval 585.1 to 833.7
|
PRIMARY outcome
Timeframe: Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60)Population: 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.
Geometric mean concentration for anti-HBs antibodies expressed as Milli-International Units per milliliter (mIU/mL).
Outcome measures
| Measure |
Twinrix Adult
n=129 Participants
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
n=119 Participants
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
|---|---|---|
|
Anti-hepatitis B (HBs) Antibody Concentrations
At year 2
|
479.9 mIU/mL
Interval 356.6 to 646.0
|
830.6 mIU/mL
Interval 609.5 to 1131.9
|
|
Anti-hepatitis B (HBs) Antibody Concentrations
At year 3
|
325.1 mIU/mL
Interval 244.7 to 431.8
|
695.1 mIU/mL
Interval 516.5 to 935.5
|
|
Anti-hepatitis B (HBs) Antibody Concentrations
At year 4
|
270.2 mIU/mL
Interval 201.0 to 363.3
|
519.7 mIU/mL
Interval 378.5 to 713.6
|
|
Anti-hepatitis B (HBs) Antibody Concentrations
At year 5
|
150.2 mIU/mL
Interval 110.5 to 204.3
|
283.7 mIU/mL
Interval 208.6 to 386.0
|
PRIMARY outcome
Timeframe: Before and one month after additional vaccinationPopulation: 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.
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Before and One month after additional vaccinationPopulation: 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.
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).
Outcome measures
| Measure |
Twinrix Adult
n=11 Participants
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
n=5 Participants
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
|---|---|---|
|
Anti-HBs Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose.
Before vaccination
|
4.9 mIU/mL
Interval 2.1 to 11.1
|
2.4 mIU/mL
Interval 0.9 to 6.5
|
|
Anti-HBs Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose.
Post vaccination
|
521.3 mIU/mL
Interval 158.2 to 1718.1
|
509.7 mIU/mL
Interval 173.5 to 1497.9
|
SECONDARY outcome
Timeframe: From last study visit of the primary study up to Year 5 long term follow-upPopulation: The analysis was performed on the Long term Total vaccinated cohort wich included all subjects who returned at a specified follow-up study
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.
Outcome measures
| Measure |
Twinrix Adult
n=139 Participants
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
n=137 Participants
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
|---|---|---|
|
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.
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: during the 4-day follow-up period after additional vaccinationPopulation: 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.
Solicited local symptoms assessed include pain, redness and swelling at the vaccine injection site. Any= regardless of intensity grade; Grade 3 Pain= spontaneously painful
Outcome measures
| Measure |
Twinrix Adult
n=11 Participants
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
n=5 Participants
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
|---|---|---|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited Local Symptoms
Pain, any
|
6 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited Local Symptoms
Pain, grade 3
|
0 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited Local Symptoms
Redness, any
|
1 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited Local Symptoms
Redness, >20mm
|
0 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited Local Symptoms
Swelling, any
|
0 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited Local Symptoms
Swelling, >20mm
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: During the 4-day follow-up period after additional vaccinationPopulation: 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.
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
Outcome measures
| Measure |
Twinrix Adult
n=11 Participants
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
n=5 Participants
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
|---|---|---|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Gastrointestinal, grade 3
|
0 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Fatigue, any
|
3 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Fatigue, grade 3
|
0 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Fatigue, related
|
3 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Fever (axillary), ≥37°C
|
0 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Fever (axillary), >39.5°C
|
0 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Fever (axillary), related
|
0 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Gastrointestinal, any
|
2 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Gastrointestinal, related
|
2 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Headache, any
|
4 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Headache, grade 3
|
0 Participants
|
0 Participants
|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Headache, related
|
4 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: During the 30-day follow-up period after additional vaccination.Population: 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.
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.
Outcome measures
| Measure |
Twinrix Adult
n=11 Participants
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
n=5 Participants
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
|---|---|---|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Unsolicited Adverse Events (AEs).
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At least one month after additional vaccinationPopulation: 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.
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.
Outcome measures
| Measure |
Twinrix Adult
n=11 Participants
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
n=5 Participants
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
|---|---|---|
|
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Any Serious Adverse Events
|
0 Participants
|
0 Participants
|
Adverse Events
Twinrix Adult
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Twinrix Junior
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Twinrix Adult
n=11 participants at risk；n=139 participants at risk
Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).
|
Twinrix Junior
n=5 participants at risk；n=137 participants at risk
Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.1%
1/11 • 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
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.
|
0.00%
0/5 • 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
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.
|
|
Nervous system disorders
Syncope vasovagal
|
9.1%
1/11 • 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
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.
|
0.00%
0/5 • 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
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.
|
|
Reproductive system and breast disorders
Balanitis
|
9.1%
1/11 • 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
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.
|
0.00%
0/5 • 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
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.
|
|
General disorders
Redness at the injection site
|
9.1%
1/11 • 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
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.
|
0.00%
0/5 • 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
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.
|
|
General disorders
Pain at the injection site
|
54.5%
6/11 • 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
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.
|
0.00%
0/5 • 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
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.
|
|
General disorders
Fatigue
|
27.3%
3/11 • 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
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.
|
0.00%
0/5 • 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
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.
|
|
General disorders
Gastrointestinal disorder
|
18.2%
2/11 • 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
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.
|
0.00%
0/5 • 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
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.
|
|
General disorders
Headache
|
36.4%
4/11 • 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
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.
|
0.00%
0/5 • 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
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.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER