Trial Outcomes & Findings for Long-term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,1,6 Mth Schedule in Healthy Adults (NCT NCT00289770)

NCT ID: NCT00289770

Last Updated: 2018-08-17

Results Overview

Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 50 participants
• Primary outcome timeframe: Years 11, 12, 13, 14 and 15
• Results posted on: 2018-08-17

Participant Flow

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.

Participant milestones

Measure	Twinrix Group 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
Year 11 STARTED	37
Year 11 COMPLETED	37
Year 11 NOT COMPLETED	0
Year 12 STARTED	40
Year 12 COMPLETED	40
Year 12 NOT COMPLETED	0
Year 13 STARTED	37
Year 13 COMPLETED	37
Year 13 NOT COMPLETED	0
Year 14 STARTED	43
Year 14 COMPLETED	43
Year 14 NOT COMPLETED	0
Year 15 STARTED	50
Year 15 COMPLETED	49
Year 15 NOT COMPLETED	1

Reasons for withdrawal

Measure	Twinrix Group 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
Year 15 Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Twinrix Group n=50 Participants 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
Age, Continuous	34.4 Years STANDARD_DEVIATION 2.66 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Years 11, 12, 13, 14 and 15

Population: 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.

Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity.

Outcome measures

Measure	Twinrix Group n=31 Participants 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
Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value Year 11	25 Participants
Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value Year 12	28 Participants
Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value Year 13	23 Participants
Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value Year 14	24 Participants
Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value Year 15	31 Participants

PRIMARY outcome

Timeframe: Years 11, 12, 13, 14 and 15

Population: 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.

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.

Outcome measures

Measure	Twinrix Group n=31 Participants 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
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 11 3.3 mIU/mL	23 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 12 3.3 mIU/mL	25 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 13 3.3 mIU/mL	20 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 14 3.3 mIU/mL	21 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 14 6.2 mIU/mL	21 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 15 6.2 mIU/mL	28 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 11 10 mIU/mL	23 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 12 10 mIU/mL	25 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 13 10 mIU/mL	20 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 14 10 mIU/mL	21 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values Year 15 10 mIU/mL	28 Participants

PRIMARY outcome

Timeframe: Years 11, 12, 13, 14 and 15

Population: 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.

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*).

Outcome measures

Measure	Twinrix Group n=31 Participants 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
Anti-HAV and Anti-HBs Antibody Concentrations Year 11 anti-HAV	680.3 mIU/mL Interval 453.8 to 1019.9
Anti-HAV and Anti-HBs Antibody Concentrations Year 12 anti-HAV	602.7 mIU/mL Interval 420.8 to 863.2
Anti-HAV and Anti-HBs Antibody Concentrations Year 13 anti-HAV	601.5 mIU/mL Interval 408.7 to 885.4
Anti-HAV and Anti-HBs Antibody Concentrations Year 14 anti-HAV	524.7 mIU/mL Interval 368.7 to 746.5
Anti-HAV and Anti-HBs Antibody Concentrations Year 15 anti-HAV	610.7 mIU/mL Interval 443.1 to 841.6
Anti-HAV and Anti-HBs Antibody Concentrations Year 11 anti-HBs	458.9 mIU/mL Interval 257.4 to 817.8
Anti-HAV and Anti-HBs Antibody Concentrations Year 12 anti-HBs	475.8 mIU/mL Interval 284.4 to 795.9
Anti-HAV and Anti-HBs Antibody Concentrations Year 13 anti-HBs	163.3 mIU/mL Interval 99.7 to 267.3
Anti-HAV and Anti-HBs Antibody Concentrations Year 14 anti-HBs	149.1 mIU/mL Interval 94.8 to 234.5
Anti-HAV and Anti-HBs Antibody Concentrations Year 14* anti-HBs	242.8 mIU/mL Interval 127.0 to 464.3
Anti-HAV and Anti-HBs Antibody Concentrations Year 15 anti-HBs	210.9 mIU/mL Interval 121.5 to 366.2

PRIMARY outcome

Timeframe: at Year 11, pre-additional vaccine, after additional dose of Engerix

Population: 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.

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.

Outcome measures

Measure	Twinrix Group n=2 Participants 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
Anti-HBs Antibody Concentrations subject 1 Year 11	3.29 mIU/mL
Anti-HBs Antibody Concentrations subject 2 Year 11	3.29 mIU/mL
Anti-HBs Antibody Concentrations subject 1 before additional dose	3.29 mIU/mL
Anti-HBs Antibody Concentrations subject 2 before additional dose	14.5 mIU/mL
Anti-HBs Antibody Concentrations subject 1 after additional dose	6548.1 mIU/mL
Anti-HBs Antibody Concentrations subject 2 after additional dose	554.0 mIU/mL

PRIMARY outcome

Timeframe: 30 days post additional dose of Engerix

Population: 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.

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.

Outcome measures

Measure	Twinrix Group n=2 Participants 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
Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response	2 Participants

PRIMARY outcome

Timeframe: During the 4-day follow-up period after additional vaccination with Engerix

Population: 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.

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

Outcome measures

Measure	Twinrix Group n=2 Participants 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
Number of Subjects With Solicited Local and General Symptoms Assessed Pain	0 Participants
Number of Subjects With Solicited Local and General Symptoms Assessed Redness	0 Participants
Number of Subjects With Solicited Local and General Symptoms Assessed Swelling	0 Participants
Number of Subjects With Solicited Local and General Symptoms Assessed Fatigue	1 Participants
Number of Subjects With Solicited Local and General Symptoms Assessed Fever	0 Participants
Number of Subjects With Solicited Local and General Symptoms Assessed Gastrointestinal	1 Participants
Number of Subjects With Solicited Local and General Symptoms Assessed Headache	0 Participants

PRIMARY outcome

Timeframe: During the 30-day follow-up period after additional Engerix vaccination

Population: 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.

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.

Outcome measures

Measure	Twinrix Group n=2 Participants 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
Number of Subjects With Unsolicited Symptoms	1 Participants

PRIMARY outcome

Timeframe: During the 30-day follow-up period after additional Engerix vaccination

Population: 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.

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

Outcome measures

Measure	Twinrix Group n=2 Participants 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
Number of Subjects With Serious Adverse Events (SAEs)	0 Participants

PRIMARY outcome

Timeframe: up to Year 11, 12, 13, 14, 15

Population: 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.

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.

Outcome measures

Measure	Twinrix Group n=50 Participants 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
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 Year 11	0 Participants
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 Year 12	0 Participants
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 Year 13	0 Participants
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 Year 14	0 Participants
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 Year 15	0 Participants

Adverse Events

Twinrix Group

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Twinrix Group n=2 participants at risk；n=50 participants at risk 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
General disorders Fatigue	50.0% 1/2 • 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). 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.
General disorders Gastrointestinal	50.0% 1/2 • 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). 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.
Eye disorders Heaviness sensation above eyes	50.0% 1/2 • 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). 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.

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