Trial Outcomes & Findings for Antibody Persistence & Immune Memory in Healthy Adults Previously Vaccinated With Twinrix Adult (NCT NCT01000324)

Last Updated: 2018-09-04

Results Overview

Seropositivity for anti-HAV antibodies is defined as antibody concentrations \>= 15 milliinternational units per milliliter (mIU/mL). Seropositivity for anti-HBs antibodies is defined as antibody concentrations \>= 6.2 mIU/mL.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

44 participants

Primary outcome timeframe

At Years 16, 17, 18, 19 and 20.

Results posted on

2018-09-04

Participant Flow

Subjects who entered the study at Years 16, 17, 18, 19 and 20 time points were subjects who completed the primary study and who returned for blood sampling at the considered time point. At Year 19 time point, one subject was given a challenge dose of Engerix.

Participant milestones

Participant milestones
Measure	Twinrix Group Pooled group of subjects from groups 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 16 STARTED	40
Year 16 COMPLETED	40
Year 16 NOT COMPLETED	0
Year 17 STARTED	32
Year 17 COMPLETED	32
Year 17 NOT COMPLETED	0
Year 18 STARTED	29
Year 18 COMPLETED	29
Year 18 NOT COMPLETED	0
Year 19 STARTED	28
Year 19 COMPLETED	28
Year 19 NOT COMPLETED	0
Year 20 STARTED	28
Year 20 COMPLETED	28
Year 20 NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Number of participants at year 16 are equal to the overall number of participants analyzed, which represents the highest number of participants from year 16 to year 20.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Twinrix Group n=40 Participants Pooled group of subjects from groups 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	39.6 Years STANDARD_DEVIATION 1.4 • n=28 Participants • Number of participants analyzed represents all subjects who returned at the year 20 annual time point.
Sex: Female, Male Female	23 Participants n=28 Participants • Number of participants analyzed represents all subjects who returned at the year 20 annual time point.
Sex: Female, Male Male	5 Participants n=28 Participants • Number of participants analyzed represents all subjects who returned at the year 20 annual time point.

PRIMARY outcome

Timeframe: At Years 16, 17, 18, 19 and 20.

Population: The analysis was performed on the Long-Term (LT) According-to-Protocol (ATP) cohort for analysis of immunogenicity. They were included in the ATP analysis for the primary study, did not receive hepatitis A or B (hep A/B) vaccination that was not specified in the protocol and were not eliminated for abnormal increase of antibody concentrations.

Outcome measures

Outcome measures
Measure	Twinrix Group n=23 Participants Pooled group of subjects from groups 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 Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) Anti-HAV >=15 mIU/mL [at Year 16] (N=23)	23 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HBs >= 6.2 mIU/mL [at Year 16] (N=23)	20 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HBs >= 10 mIU/mL [at Year 16] (N=23)	20 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HAV >= 15 mIU/mL [at Year 17] (N=19)	19 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HBs >= 6.2 mIU/mL [at Year 17] (N=19)	17 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HBs >= 10 mIU/mL [at Year 17] (N=19)	17 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HAV >= 15 mIU/mL [at Year 18] (N=10)	10 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HBs >= 6.2 mIU/mL [at Year 18] (N=10)	9 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HBs >= 10 mIU/mL [at Year 18] (N=10)	9 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HAV >= 15 mIU/mL [at Year 19] (N=17)	17 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HBs >= 6.2 mIU/mL [at Year 19] (N=18)	17 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HBs >= 10 mIU/mL [at Year 19] (N=18)	17 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HAV >= 15 mIU/mL [at Year 20] (N=18)	18 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HBs >= 6.2 mIU/mL [at Year 20] (N=18)	17 Subjects
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) anti-HBs >= 10 mIU/mL [at Year 20] (N=18)	17 Subjects

PRIMARY outcome

Timeframe: At Years 16, 17, 18, 19 and 20.

Population: The analysis was performed on the Long-Term (LT) According-to-Protocol (ATP) cohort for analysis of immunogenicity.They were included in the ATP analysis for the primary study, did not receive hepatitis A or B vaccination that was not specified in the protocol and were not eliminated for abnormal increase of antibody concentrations.

Concentrations were expressed as GMCs in mIU/mL.

Outcome measures

Outcome measures
Measure	Twinrix Group n=23 Participants Pooled group of subjects from groups 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 Geometric Mean Concentrations (GMCs) anti-HBs [at Year 20] (N=18)	195.8 milli-international units per milliliter Interval 79.9 to 480.0
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) anti-HAV [at Year 16] (N=23)	614.2 milli-international units per milliliter Interval 404.1 to 933.6
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) anti-HBs [at Year 16] (N=23)	138.7 milli-international units per milliliter Interval 61.3 to 313.7
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) anti-HAV [at Year 17] (N=19)	479.2 milli-international units per milliliter Interval 298.2 to 769.9
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) anti-HBs [at Year 17] (N=19)	165.1 milli-international units per milliliter Interval 64.8 to 420.7
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) anti-HAV [at Year 18] (N=10)	653.2 milli-international units per milliliter Interval 333.2 to 1280.6
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) anti-HBs [at Year 18] (N=10)	278.3 milli-international units per milliliter Interval 70.3 to 1101.3
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) anti-HAV [at Year 19] (N=17)	728.7 milli-international units per milliliter Interval 469.6 to 1130.5
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) anti-HBs [at Year 19] (N=18)	198.4 milli-international units per milliliter Interval 80.1 to 491.3
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) anti-HAV [at Year 20] (N=18)	511.9 milli-international units per milliliter Interval 343.8 to 762.0

SECONDARY outcome

Timeframe: Before, 14 days and one month after the challenge dose at Year 19.

Population: The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study.

None of the subjects received a challenge dose at Years 16, 17, 18 and 20 while, one subject received the challenge dose at Year 19.

Outcome measures

Outcome measures
Measure	Twinrix Group n=1 Participants Pooled group of subjects from groups 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 Immune Response to the Challenge Vaccine Antigen	1 Subjects

SECONDARY outcome

Timeframe: At Year 18, 14 days and 30 days post challenge dose (Year 19).

Population: The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study.

Concentrations are given as Geometric Mean Concentrations (GMCs) expressed as mIU/mL.

Outcome measures

Outcome measures
Measure	Twinrix Group n=1 Participants Pooled group of subjects from groups 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-hepatitis B Virus (Anti-HBs) Antibody Concentration [Subject 1; at year 18]	13.26 milli-international units per milliliter One subject received the challenge dose at Year 19.
Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration [Subject 1; 14 days post challenge dose]	21926.00 milli-international units per milliliter One subject received the challenge dose at Year 19.
Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration [Subject 1; 30 days post challenge dose]	12736.00 milli-international units per milliliter One subject received the challenge dose at Year 19.

SECONDARY outcome

Timeframe: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.

Population: The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study

An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.

Outcome measures

Outcome measures
Measure	Twinrix Group n=1 Participants Pooled group of subjects from groups 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 Reporting Unsolicited Adverse Events (AE)	1 Subjects

SECONDARY outcome

Timeframe: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.

Population: The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study.

A serious adverse event was any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

Outcome measures

Outcome measures
Measure	Twinrix Group n=1 Participants Pooled group of subjects from groups 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 Reporting Serious Adverse Events (SAEs)	0 Subjects

SECONDARY outcome

Timeframe: Up to Year 20.

Population: The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study.

A serious adverse event is any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, or was a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

Outcome measures

Outcome measures
Measure	Twinrix Group n=40 Participants Pooled group of subjects from groups 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 Reporting Serious Adverse Events (SAEs)	0 Subjects

Adverse Events

Twinrix Group

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Twinrix Group n=1 participants at risk；n=40 participants at risk Pooled group of subjects from groups 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
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	100.0% 1/1 • Number of events 1 • SAEs: During the 31-day (Days 0 to 30) follow-up period after the challenge dose and from the beginning of the long term follow-up to Year 20; Unsolicited symptoms: During the 31-day (Days 0 to 30) follow-up period after the challenge dose. As no challenge dose was administered during Years 16, 17, 18 and 20 time points, SAEs and other adverse events were not assessed. 1 subject received the challenge dose at Year 19 for whom the SAEs and other adverse events were assessed during the 31 day period post challenge dose. SAEs were also collected for the entire safety follow-up.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	100.0% 1/1 • Number of events 1 • SAEs: During the 31-day (Days 0 to 30) follow-up period after the challenge dose and from the beginning of the long term follow-up to Year 20; Unsolicited symptoms: During the 31-day (Days 0 to 30) follow-up period after the challenge dose. As no challenge dose was administered during Years 16, 17, 18 and 20 time points, SAEs and other adverse events were not assessed. 1 subject received the challenge dose at Year 19 for whom the SAEs and other adverse events were assessed during the 31 day period post challenge dose. SAEs were also collected for the entire safety follow-up.

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