Trial Outcomes & Findings for Evaluation of Antibody Persistence and Immune Memory Against the Hepatitis B Antigen in Previously Vaccinated Children (NCT NCT01138098)

NCT ID: NCT01138098

Last Updated: 2018-08-20

Results Overview

A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

185 participants

Primary outcome timeframe

One month after a challenge dose of Engerix-B vaccine

Results posted on

2018-08-20

Participant Flow

Participant milestones

Participant milestones
Measure
Infanrix-hexa/Engerix-B Group
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Overall Study
STARTED
95
90
Overall Study
COMPLETED
95
90
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Infanrix-hexa/Engerix-B Group
n=95 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=90 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Total
n=185 Participants
Total of all reporting groups
Age, Continuous
11.3 Years
STANDARD_DEVIATION 0.46 • n=95 Participants
11.3 Years
STANDARD_DEVIATION 0.47 • n=90 Participants
11.3 Years
STANDARD_DEVIATION 0.47 • n=185 Participants
Sex: Female, Male
Female
45 Participants
n=95 Participants
35 Participants
n=90 Participants
80 Participants
n=185 Participants
Sex: Female, Male
Male
50 Participants
n=95 Participants
55 Participants
n=90 Participants
105 Participants
n=185 Participants
Race and Ethnicity Not Collected
0 Participants
Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: One month after a challenge dose of Engerix-B vaccine

Population: The According-To-Protocol (ATP) cohort for analysis of immunogenicity included all evaluable subjects (i.e. those meeting eligibility criteria, complied with the procedures, with no elimination criteria) who had received a challenge dose Engerix-B vaccine and for whom immunogenicity data were available at the post-Engerix-B challenge time-point.

A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.

Outcome measures

Outcome measures
Measure
Infanrix-hexa/Engerix-B Group
n=94 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=89 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL)
88 Participants
84 Participants

SECONDARY outcome

Timeframe: Before and one month after a challenge dose of Engerix-B vaccine

Population: The According-To-Protocol (ATP) cohort for analysis of immunogenicity included all evaluable subjects (i.e. those meeting eligibility criteria, complied with the procedures, with no elimination criteria) who had received a challenge dose Engerix-B vaccine and for whom immunogenicity data were available at the post-Engerix-B challenge time-point.

The anamnestic response was defined as: at least (≥) a 4-fold rise in post-challenge dose anti-HBs antibody concentrations in subjects seropositive at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations ≥ 10 mIU/mL in seronegative subjects at the pre-challenge dose time point. A seropositive/seronegative subject is a subject with anti-HBs antibody concentration ≥/lower than (\<) 6.2 mIU/mL. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off.

Outcome measures

Outcome measures
Measure
Infanrix-hexa/Engerix-B Group
n=94 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=89 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Number of Subjects With an Anamnestic Response to a Challenge Dose
91 Participants
86 Participants

SECONDARY outcome

Timeframe: Before and one month after a challenge dose of Engerix-B vaccine

Population: The According-To-Protocol (ATP) cohort for analysis of immunogenicity included all evaluable subjects (i.e. those meeting eligibility criteria, complied with the procedures, with no elimination criteria) who had received a challenge dose Engerix-B vaccine and for whom immunogenicity data were available at the post-Engerix-B challenge time-point.

A seropositive subject was defined as a subject with anti-HBs antibody concentration ≥ the 6.2 mIU/mLcut-off. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off.

Outcome measures

Outcome measures
Measure
Infanrix-hexa/Engerix-B Group
n=95 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=89 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL
≥ 6.2 mIU/mL [pre-challenge dose]
53 Participants
57 Participants
Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL
≥ 6.2 mIU/mL [post-challenge dose]
92 Participants
88 Participants

SECONDARY outcome

Timeframe: Before and one month after a challenge dose of Engerix-B vaccine

Population: The According-To-Protocol (ATP) cohort for analysis of immunogenicity included all evaluable subjects (i.e. those meeting eligibility criteria, complied with the procedures, with no elimination criteria) who had received a challenge dose Engerix-B vaccine and for whom immunogenicity data were available at the post-Engerix-B challenge time-point.

A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.

Outcome measures

Outcome measures
Measure
Infanrix-hexa/Engerix-B Group
n=95 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=89 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL
≥ 10 mIU/mL [pre-challenge dose]
46 Participants
52 Participants
Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL
≥ 10 mIU/mL [post-challenge dose]
91 Participants
88 Participants

SECONDARY outcome

Timeframe: Before the challenge dose of Engerix-B vaccine

Population: The According-To-Protocol (ATP) cohort for analysis of immunogenicity included all evaluable subjects (i.e. those meeting eligibility criteria, complied with the procedures, with no elimination criteria) who had received a challenge dose Engerix-B vaccine and for whom immunogenicity data were available at the post-Engerix-B challenge time-point.

A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.

Outcome measures

Outcome measures
Measure
Infanrix-hexa/Engerix-B Group
n=95 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=89 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Number of Subjects With Anti-HBs Antibody Concentration ≥ 100 mIU/mL
14 Participants
17 Participants

SECONDARY outcome

Timeframe: During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine

Population: The Total Vaccinated cohort included all subjects who received the challenge dose of Engerix-B vaccine.

Solicited local symptoms assessed were pain, redness and swelling.

Outcome measures

Outcome measures
Measure
Infanrix-hexa/Engerix-B Group
n=95 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=90 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Number of Subjects Reporting Solicited Local Symptoms
Pain
30 Participants
24 Participants
Number of Subjects Reporting Solicited Local Symptoms
Redness
25 Participants
22 Participants
Number of Subjects Reporting Solicited Local Symptoms
Swelling
15 Participants
8 Participants

SECONDARY outcome

Timeframe: During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine

Population: The Total Vaccinated cohort included all subjects who received the challenge dose of Engerix-B vaccine.

Solicited general symptoms assessed were fatigue, gastrointestinal, headache and temperature (Temperature is defined as axillary temparature equal to or above 37.5 degrees Celsius (°C)).

Outcome measures

Outcome measures
Measure
Infanrix-hexa/Engerix-B Group
n=95 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=90 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Number of Subjects Reporting Solicited General Symptoms
Fatigue
23 Participants
22 Participants
Number of Subjects Reporting Solicited General Symptoms
Gastrointestinal
9 Participants
9 Participants
Number of Subjects Reporting Solicited General Symptoms
Headache
19 Participants
14 Participants
Number of Subjects Reporting Solicited General Symptoms
Temperature ≥ 37.5°C
1 Participants
3 Participants

SECONDARY outcome

Timeframe: During the 31-day (Days 0-30) follow-up period after a challenge dose of Engerix-B vaccine

Population: The Total Vaccinated cohort included all subjects who received the challenge dose of Engerix-B vaccine.

An unsolicited adverse event is any adverse event (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.

Outcome measures

Outcome measures
Measure
Infanrix-hexa/Engerix-B Group
n=95 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=90 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
5 Participants
7 Participants

SECONDARY outcome

Timeframe: After the challenge dose of Engerix-B vaccine up to the study end

Population: The Total Vaccinated cohort included all subjects who received the challenge dose of Engerix-B vaccine.

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

Outcome measures

Outcome measures
Measure
Infanrix-hexa/Engerix-B Group
n=95 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=90 Participants
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Number of Subjects Reporting Serious Adverse Events (SAEs)
1 Participants
0 Participants

Adverse Events

Infanrix-hexa/Engerix-B Group

Serious events: 1 serious events
Other events: 48 other events
Deaths: 0 deaths

Infanrix-IPV+Hib/Engerix-B Group

Serious events: 0 serious events
Other events: 43 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Infanrix-hexa/Engerix-B Group
n=95 participants at risk
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=90 participants at risk
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infections and infestations
Infection
1.1%
1/95 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
0.00%
0/90 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end

Other adverse events

Other adverse events
Measure
Infanrix-hexa/Engerix-B Group
n=95 participants at risk
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Infanrix-IPV+Hib/Engerix-B Group
n=90 participants at risk
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
General disorders
Pain
31.6%
30/95 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
26.7%
24/90 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
General disorders
Redness
26.3%
25/95 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
24.4%
22/90 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
General disorders
Swelling
15.8%
15/95 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
8.9%
8/90 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
General disorders
Fatigue
24.2%
23/95 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
24.4%
22/90 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
General disorders
Gastrointestinal
9.5%
9/95 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
10.0%
9/90 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
General disorders
Headache
20.0%
19/95 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end
15.6%
14/90 • Solicited symptoms: During the 4-day (Days 0-3) follow-up period after the challenge dose of Engerix-B vaccine. SAEs: after the challenge dose of Engerix-B vaccine up to the study end

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