Trial Outcomes & Findings for Long-Term Immune Persistence of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine, Injected According to 0, 6-month Schedule (NCT NCT00289757)

Results Overview

Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL). The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

78 participants

Primary outcome timeframe

At Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination

Results posted on

2018-07-23

Participant Flow

Participant Flow and Baseline measures are given for the Month 192 (Year 16) time point in order to account for all subjects participating in this long-term follow-up study. Note that not all subjects returned and participated in each of the intermediate follow-up time points.

The Long-Term (LT) Total Cohort included all subjects who returned for the follow-up and who belonged to the Total Cohort in the primary study.The Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity included subjects who returned for the follow-up and who were included in the ATP cohort for immunogenicity of the primary study.

Participant milestones

Participant milestones
Measure	Havrix Group Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
Overall Study STARTED	78
Overall Study COMPLETED	78
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Long-Term Immune Persistence of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine, Injected According to 0, 6-month Schedule

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Havrix Group n=78 Participants Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
Age, Continuous	42.3 years STANDARD_DEVIATION 7.00 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination

Population: Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity, on subjects with available data for the defined timepoint.

Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL). The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging.

Outcome measures

Outcome measures
Measure	Havrix Group n=53 Participants Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 11 Old Assay Method (N=43)	593.6 mIU/mL Interval 452.0 to 779.5
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 11 New Assay Method (N=46)	297.4 mIU/mL Interval 220.1 to 401.8
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 12 (N=42)	363.2 mIU/mL Interval 263.1 to 501.2
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 13 (N=50)	287.7 mIU/mL Interval 218.6 to 378.6
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 14 (N=46)	270.4 mIU/mL Interval 196.5 to 372.1
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 15 (N=41)	290.3 mIU/mL Interval 210.7 to 400.1
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 16 (N=53)	242.3 mIU/mL Interval 182.8 to 321.3
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 17 (N=45)	277.9 mIU/mL Interval 206.5 to 374.0
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 18 (N=37)	301.7 mIU/mL Interval 211.2 to 431.1
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 19 (N=26)	226.5 mIU/mL Interval 154.8 to 331.3
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 20 (N=34)	311.8 mIU/mL Interval 233.2 to 416.8

PRIMARY outcome

Timeframe: Before the additional dose, 14 days and 30 days after the additional dose

Population: Analysis was performed on the Long Term Total cohort, only on subjects who received an additional vaccine dose during the current long-term follow-up study. If a subject became seronegative (\< 15 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose.

Concentrations given as GMC expressed as mIU/mL.

Outcome measures

Outcome measures
Measure	Havrix Group n=2 Participants Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 1 (pre-additional dose)	23 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 1 (14 days post-additional dose)	702 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 1 (30 days post-additional dose)	836 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 2 (pre-additional dose)	24 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 2 (14 days post-additional dose)	6107 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 2 (30 days post-additional dose)	5939 mIU/mL

PRIMARY outcome

Timeframe: From Year 11 to Year 20

Population: Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity, on subjects with available data for the defined timepoint.

Seropositivity for anti-HAV antibodies defined as antibody concentrations ≥ 15 mIU/mL for Year 11 to Year 20 time points. The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging.

Outcome measures

Outcome measures
Measure	Havrix Group n=53 Participants Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 14 (N=46)	46 Subjects
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 11 Old Assay Method (N=43)	43 Subjects
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 11 New Assay Method (N=46)	46 Subjects
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 12 (N=42)	42 Subjects
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 13 (N=50)	50 Subjects
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 15 (N=41)	41 Subjects
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 16 (N=53)	53 Subjects
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 17 (N=45)	45 Subjects
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 18 (N=37)	37 Subjects
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 19 (N=26)	26 Subjects
Number of Seropositive Subjects for Anti-HAV Antibodies. Year 20 (N=34)	34 Subjects

SECONDARY outcome

Timeframe: Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination

Population: Analysis was performed on the Long Term Total cohort which included all subjects who returned to the follow-up study and who had received at least 1 dose of the vaccine in the primary study.

An 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

Outcome measures
Measure	Havrix Group n=78 Participants Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy Year 11 (N=64)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy Year 12 (N=60)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy Year 13 (N=71)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy Year 14 (N=66)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy Year 15 (N=63)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy Year 16 (N=78)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy Year 17 (N=63)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy Year 18 (N=52)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy Year 19 (N=45)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy Year 20 (N=50)	0 Subjects

SECONDARY outcome

Timeframe: During the 4-day (Day 0-3) follow-up period after additional vaccination

Population: Analysis was performed on the Long Term Total cohort, only on subjects who received an additional vaccine dose during the current long-term follow-up study. If a subject became seronegative (\< 15 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose.

Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain = symptom that prevented normal activities. Grade 3 redness and swelling = redness or swelling above 30 mm and persisting more than 24 hours. Any = incidence of a particular symptom regardless of intensity.

Outcome measures

Outcome measures
Measure	Havrix Group n=2 Participants Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Any Pain	1 Subjects
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Any Redness	0 Subjects
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Any Swelling	0 Subjects
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Grade 3 Pain	0 Subjects
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Grade 3 Redness > 30 mm	0 Subjects
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Grade 3 Swelling > 30 mm	0 Subjects

SECONDARY outcome

Timeframe: During the 4-day (Day 0-3) follow-up period after additional vaccination

Population: Analysis was performed on the Long Term Total cohort, only on subjects who received an additional vaccine dose during the current long-term follow-up study. If a subject became seronegative (\< 15 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose.

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

Outcome measures

Outcome measures
Measure	Havrix Group n=2 Participants Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms Any, Grade 3 and Related Fatigue	0 Subjects
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms Any, Grade 3 and Related Fever	0 Subjects
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms Any, Grade 3 and Related Gastrointestinal	0 Subjects
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms Any, Grade 3 and Related Headache	0 Subjects

SECONDARY outcome

Timeframe: During the 30-day follow-up period after additional vaccination (for subjects who received the additional vaccine dose between Year 11 and 15)

Population: Analysis was performed on the Long Term Total cohort, only on subjects who received an additional vaccine dose during the current long-term follow-up study. If a subject became seronegative (\< 15 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose.

An AE 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. Grade AE = produced significant impairment of functioning or incapacitation and was a definite hazard to the subject's health. Related AE = assessed by the investigator as related to the study vaccination.

Outcome measures

Outcome measures
Measure	Havrix Group n=2 Participants Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AE) Any AE(s)	1 Subjects
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AE) Grade 3 AE(s)	0 Subjects
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AE) AE(s) Related	0 Subjects

SECONDARY outcome

Timeframe: During the follow-up period after additional vaccination up to Year 20

Population: Analysis was performed on the Long Term Total cohort, only on subjects who received an additional vaccine dose during the current long-term follow-up study. If a subject became seronegative (\< 15 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose.

An 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

Outcome measures
Measure	Havrix Group n=2 Participants Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
Number of Subjects Reporting Serious Adverse Events (SAE)	0 Subjects

Adverse Events

Havrix 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

Other adverse events
Measure	Havrix Group n=2 participants at risk；n=78 participants at risk Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up
General disorders Pain	50.0% 1/2 • Until year 20 for SAEs and within 4-days after additional vaccination for other AEs. During the 30-day (Day 0 to Day 29) follow-up period after additional vaccination. Analyses were performed on the Long-Term (LT) Total Cohort including subjects who returned for the follow-up and who belonged to the Total Cohort in the primary study. For the other AEs only subjects receiving an additional dose were included. Therefore the number of subjects at risk is not consistent with the LT Total Cohort.
Infections and infestations Influenza like illness	50.0% 1/2 • Until year 20 for SAEs and within 4-days after additional vaccination for other AEs. During the 30-day (Day 0 to Day 29) follow-up period after additional vaccination. Analyses were performed on the Long-Term (LT) Total Cohort including subjects who returned for the follow-up and who belonged to the Total Cohort in the primary study. For the other AEs only subjects receiving an additional dose were included. Therefore the number of subjects at risk is not consistent with the LT Total Cohort.

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