Trial Outcomes & Findings for Long-Term Immune Persistence of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine Injected According to a 0, 12-month Schedule (NCT NCT00291876)

Last Updated: 2017-11-29

Results Overview

Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL). \*\* = Regarding Month 234 data, please note that there were 5 subjects for whom serum sample tube was broken and thus due to risk of contamination the test were not performed. Hence these subjects were not included in the LT-ATP cohort for immunogenicity analysis at Month 234. $ = Regarding Month 246 data, please note there was 1 subject for whom serum sample tube was broken and hence scrapped by laboratory. Hence this subject was not included in the LT-ATP cohort for immunogenicity analysis at Month 246.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

135 participants

Primary outcome timeframe

At Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246

Results posted on

2017-11-29

Participant Flow

Participant Flow and Baseline Measures are given for each of the follow-up time points- Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246. 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 during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Month 138 STARTED	107
Month 138 COMPLETED	107
Month 138 NOT COMPLETED	0
Month 150 STARTED	117
Month 150 COMPLETED	117
Month 150 NOT COMPLETED	0
Month 162 STARTED	127
Month 162 COMPLETED	127
Month 162 NOT COMPLETED	0
Month 174 STARTED	127
Month 174 COMPLETED	127
Month 174 NOT COMPLETED	0
Month 186 STARTED	129
Month 186 COMPLETED	129
Month 186 NOT COMPLETED	0
Month 198 STARTED	135
Month 198 COMPLETED	135
Month 198 NOT COMPLETED	0
Month 210 STARTED	124
Month 210 COMPLETED	124
Month 210 NOT COMPLETED	0
Month 222 STARTED	114
Month 222 COMPLETED	114
Month 222 NOT COMPLETED	0
Month 234 STARTED	110
Month 234 COMPLETED	110
Month 234 NOT COMPLETED	0
Month 246 STARTED	116
Month 246 COMPLETED	116
Month 246 NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Note that not all subjects returned and participated in each of the intermediate follow-up time points.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Havrix Group n=135 Participants Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Age, Continuous	50.8 Years STANDARD_DEVIATION 5.34 • n=116 Participants • Note that not all subjects returned and participated in each of the intermediate follow-up time points.
Sex: Female, Male Female	86 Participants n=116 Participants • Note that not all subjects returned and participated in each of the intermediate follow-up time points.
Sex: Female, Male Male	30 Participants n=116 Participants • Note that not all subjects returned and participated in each of the intermediate follow-up time points.

PRIMARY outcome

Timeframe: At Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246

Population: Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for analysis of immunogenicity, on subjects with available data for the defined timepoint. \* The laboratory assay was changed at Month 138, thus the blood samples were re-tested with the old assay for the sake of bridging.

Outcome measures

Outcome measures
Measure	Havrix Group n=102 Participants Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 138 (N=79)	748.1 mIU/mL Interval 614.3 to 911.1
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 138 (N=85)*	378.6 mIU/mL Interval 304.3 to 471.0
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 150 (N=93)	419.3 mIU/mL Interval 335.1 to 524.8
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 162 (N=101)	342.2 mIU/mL Interval 270.8 to 432.5
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 174 (N=102)	318.9 mIU/mL Interval 257.0 to 395.5
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 186 (N=98)	353.1 mIU/mL Interval 284.0 to 439.1
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 198 (N=101)	339.9 mIU/mL Interval 273.2 to 422.9
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 210 (N=91)	369.3 mIU/mL Interval 294.0 to 463.9
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 222 (N=86)	340.1 mIU/mL Interval 271.1 to 426.7
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 234 (N=79)**	283.3 mIU/mL Interval 222.4 to 361.0
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Month 246 (N=85)$	317.3 mIU/mL Interval 247.4 to 407.1

PRIMARY outcome

Timeframe: At Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246

Population: Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for analysis of immunogenicity, on subjects with available data for the defined timepoint. \*The laboratory assay was changed at Month 138, thus the blood samples were re-tested with the old assay for the sake of bridging.

A seropositive subject was a vaccinated subject whose concentrations for antibodies against hepatitis A virus (anti-HAV) were equal or above (\>=) the assay cut-off for seropositivity of 15 milli-international units per milliliter (mIU/mL). \*\* = Regarding Month 234 data, please note that there were 5 subjects for whom serum sample tube was broken and thus due to risk of contamination the test were not performed. Hence these subjects were not included in the LT-ATP cohort for immunogenicity analysis at Month 234. $ = Regarding Month 246 data, please note there was 1 subject for whom serum sample tube was broken and hence scrapped by laboratory. Hence this subject was not included in the LT-ATP cohort for immunogenicity analysis at Month 246.

Outcome measures

Outcome measures
Measure	Havrix Group n=102 Participants Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Number of Seropositive Subjects Against Hepatitis A Virus Month 186 (N=98)	95 Subjects
Number of Seropositive Subjects Against Hepatitis A Virus Month 198 (N=101)	97 Subjects
Number of Seropositive Subjects Against Hepatitis A Virus Month 210 (N=91)	88 Subjects
Number of Seropositive Subjects Against Hepatitis A Virus Month 222 (N=86)	86 Subjects
Number of Seropositive Subjects Against Hepatitis A Virus Month 234 (N=79)**	79 Subjects
Number of Seropositive Subjects Against Hepatitis A Virus Month 246 (N=85)$	85 Subjects
Number of Seropositive Subjects Against Hepatitis A Virus Month 138 (N=79)	77 Subjects
Number of Seropositive Subjects Against Hepatitis A Virus Month 138 (N=85)*	82 Subjects
Number of Seropositive Subjects Against Hepatitis A Virus Month 150 (N=93)	90 Subjects
Number of Seropositive Subjects Against Hepatitis A Virus Month 162 (N=101)	98 Subjects
Number of Seropositive Subjects Against Hepatitis A Virus Month 174 (N=102)	100 Subjects

SECONDARY outcome

Timeframe: Before additional vaccination, 14 days after additional vaccination and 30 days 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.

Concentrations given as GMC expressed as mIU/mL. 4 subjects received additional vaccination at Month 186 and 1 subject at Month 198. Please note that value 14.9 means \<15.

Outcome measures

Outcome measures
Measure	Havrix Group n=5 Participants Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 1 Month 186 before	14.9 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 1 Month 186 day 14	15 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 1 Month 186 day 30	26 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 2 Month 186 before	14.9 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 2 Month 186 day 14	453 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 2 Month 186 day 30	787 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 3 Month 186 before	15 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 3 Month 186 day 14	3102 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 3 Month 186 day 30	3819 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 4 Month 186 before	16 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 4 Month 186 day 14	1636 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 4 Month 186 day 30	2051 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 5 Month 198 before	16 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 5 Month 198 day 14	3222 mIU/mL
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Subject 5 Month 198 day 30	4894 mIU/mL

SECONDARY outcome

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

Solicited local symptoms assessed include pain, redness and swelling. Additional vaccination was given to 4 subjects at the Month 186 timepoint and to 1 subject at the Month 198 timepoint.

Outcome measures

Outcome measures
Measure	Havrix Group n=5 Participants Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Number of Subjects Reporting Solicited Local Symptoms Pain Month 186 (N=4)	2 subjects
Number of Subjects Reporting Solicited Local Symptoms Redness Month 186 (N=4)	0 subjects
Number of Subjects Reporting Solicited Local Symptoms Swelling Month 186 (N=4)	0 subjects
Number of Subjects Reporting Solicited Local Symptoms Pain Month 198 (N=1)	1 subjects
Number of Subjects Reporting Solicited Local Symptoms Redness Month 198 (N=1)	0 subjects
Number of Subjects Reporting Solicited Local Symptoms Swelling Month 198 (N=1)	0 subjects

SECONDARY outcome

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

Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms and headache. 4 subjects received additional vaccination at Month 186 and 1 subject at Month 198.

Outcome measures

Outcome measures
Measure	Havrix Group n=5 Participants Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Number of Subjects Reporting Solicited General Symptoms Fever Month 186 (N=4)	0 subjects
Number of Subjects Reporting Solicited General Symptoms Fatigue Month 186 (N=4)	2 subjects
Number of Subjects Reporting Solicited General Symptoms Gastrointestinal Month 186 (N=4)	1 subjects
Number of Subjects Reporting Solicited General Symptoms Headache Month 186 (N=4)	1 subjects
Number of Subjects Reporting Solicited General Symptoms Fatigue Month 198 (N=1)	0 subjects
Number of Subjects Reporting Solicited General Symptoms Fever Month 198 (N=1)	0 subjects
Number of Subjects Reporting Solicited General Symptoms Gastrointestinal Month 198 (N=1)	0 subjects
Number of Subjects Reporting Solicited General Symptoms Headache Month 198 (N=1)	0 subjects

SECONDARY outcome

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

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. 4 subjects received additional vaccination at Month 186 and 1 at Month 198.

Outcome measures

Outcome measures
Measure	Havrix Group n=5 Participants Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Number of Subjects Reporting Unsolicited Adverse Events (AE) Month 186 (N=4)	0 subjects
Number of Subjects Reporting Unsolicited Adverse Events (AE) Month 198 (N=1)	0 subjects

SECONDARY outcome

Timeframe: At Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246

Population: Analysis was performed on the Long Term Total cohort, on subjects with available data for the defined timepoint.

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=135 Participants Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine Efficacy Month 138 (N=107)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine Efficacy Month 150 (N=117)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine Efficacy Month 162 (N=127)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine Efficacy Month 174 (N=127)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine Efficacy Month 186 (N=129)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine Efficacy Month 198 (N=135)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine Efficacy Month 210 (N=124)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine Efficacy Month 222 (N=114)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine Efficacy Month 234 (N=110)	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine Efficacy Month 246 (N=116)	0 Subjects

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Havrix Group n=5 Participants Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Number of Subjects Reporting Serious Adverse Events (SAE) After Additional Vaccination Month 186 (N=4)	0 subjects
Number of Subjects Reporting Serious Adverse Events (SAE) After Additional Vaccination Month 198 (N=1)	0 subjects

SECONDARY outcome

Timeframe: At Months 186 and 198

The number of subjects with outcome of pregnancies reported among subjects who had received the additional vaccination was tabulated. 4 subjects received additional vaccination at Month 186 and 1 subject at Month 198.

Outcome measures

Outcome measures
Measure	Havrix Group n=5 Participants Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
Number of Subjects Reporting Pregnancies After Additional Vaccination Subjects with pregnancy - At Month 186 (N=4)	0 Subject
Number of Subjects Reporting Pregnancies After Additional Vaccination Subjects with pregnancy - At Month 198 (N=1)	0 Subject

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=5 participants at risk；n=135 participants at risk Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.
General disorders Pain	100.0% 1/1 • SAEs: At Months 138, 150, 162, 174, 186, 198, 210, 222 234 and 246. Other adverse events: within the 4-day periods after additional vaccination (at Month 186 or 198), only in subjects who received additional vaccination at the specified time point. Analyses were performed on the Long-Term (LT) Total Cohort which included all subjects who returned for the follow-up and who belonged to the Total Cohort in the primary study. Maximum amount of subjects which participated at Month 198 has been taken as the number of subjects at risk for SAEs.
General disorders Fatigue	50.0% 2/4 • SAEs: At Months 138, 150, 162, 174, 186, 198, 210, 222 234 and 246. Other adverse events: within the 4-day periods after additional vaccination (at Month 186 or 198), only in subjects who received additional vaccination at the specified time point. Analyses were performed on the Long-Term (LT) Total Cohort which included all subjects who returned for the follow-up and who belonged to the Total Cohort in the primary study. Maximum amount of subjects which participated at Month 198 has been taken as the number of subjects at risk for SAEs.
General disorders Gastrointestinal	25.0% 1/4 • SAEs: At Months 138, 150, 162, 174, 186, 198, 210, 222 234 and 246. Other adverse events: within the 4-day periods after additional vaccination (at Month 186 or 198), only in subjects who received additional vaccination at the specified time point. Analyses were performed on the Long-Term (LT) Total Cohort which included all subjects who returned for the follow-up and who belonged to the Total Cohort in the primary study. Maximum amount of subjects which participated at Month 198 has been taken as the number of subjects at risk for SAEs.
General disorders Headache	25.0% 1/4 • SAEs: At Months 138, 150, 162, 174, 186, 198, 210, 222 234 and 246. Other adverse events: within the 4-day periods after additional vaccination (at Month 186 or 198), only in subjects who received additional vaccination at the specified time point. Analyses were performed on the Long-Term (LT) Total Cohort which included all subjects who returned for the follow-up and who belonged to the Total Cohort in the primary study. Maximum amount of subjects which participated at Month 198 has been taken as the number of subjects at risk for SAEs.

Additional Information

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Phone: 866-435-7343

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