Trial Outcomes & Findings for Hepatitis B Antibody Persistence and Immune Response to Hepatitis B Vaccine Challenge in Previously Vaccinated Children (NCT NCT01333813)

NCT ID: NCT01333813

Last Updated: 2018-06-06

Results Overview

A decrease in the specificity of the anti-HBs enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of anti-HBs antibodies (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: 300 participants
• Primary outcome timeframe: One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine
• Results posted on: 2018-06-06

Participant Flow

A total of 300 subjects were enrolled in the study. Among them 297 subjects were included in the Total Vaccinated cohort. Remaining 3 subjects were not included as they failed to meet protocol specified criteria and as such they are not included in the Participant Flow as Started.

Participant milestones

Measure	Engerix-B Kinder Group Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Overall Study STARTED	297
Overall Study COMPLETED	297
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Hepatitis B Antibody Persistence and Immune Response to Hepatitis B Vaccine Challenge in Previously Vaccinated Children

Baseline characteristics by cohort

Measure	Engerix-B Kinder Group n=297 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Age, Continuous	7.5 Years STANDARD_DEVIATION 0.52 • n=5 Participants
Sex: Female, Male Female	144 Participants n=5 Participants
Sex: Female, Male Male	153 Participants n=5 Participants

PRIMARY outcome

Timeframe: One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine

Population: Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who had received a challenge dose of Engerix-B Kinder vaccine and for whom immunogenicity data were available at the post- Engerix-B Kinder challenge time point.

A decrease in the specificity of the anti-HBs enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of anti-HBs antibodies (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

Measure	Engerix-B Kinder Group n=262 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL)	251 Participants

SECONDARY outcome

Timeframe: Before (Day 0) a challenge dose of Engerix-B Kinder vaccine

Population: Analysis was performed on According-to-Protocol (ATP) cohort for persistence which included all subjects previously primed and boosted with 4 doses of Infanrix hexa in the first 2 years of life; with no evidence of hepatitis B infection or disease and for whom serological results were available at the pre- Engerix-B Kinder challenge time point.

Antibody concentrations are expressed as Geometric mean antibody concentrations (GMCs) in mIU/mL.

A decrease in the specificity of the anti-HBs ELISA had been observed in some studies for low levels of anti-HBs antibodies (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

Measure	Engerix-B Kinder Group n=287 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Anti-HBs Antibody Concentrations After Previous Vaccination With Infanrix Hexa Vaccine.	36.6 mIU/mL Interval 29.7 to 45.1

SECONDARY outcome

Timeframe: Before (Day 0) a challenge dose of Engerix-B Kinder vaccine

Population: Analysis was performed on According-to-Protocol (ATP) cohort for persistence which included all subjects previously primed and boosted with 4 doses of Infanrix hexa in the first 2 years of life; with no evidence of hepatitis B infection or disease and for whom serological results were available at the pre- Engerix-B Kinder challenge time point.

Anti-HBs antibody concentrations cut-off values assessed were ≥ 6.2 mIU/mL (previously 3.3 mIU/mL), ≥ 10 mIU/mL, ≥ 10 mIU/mL to <100 mIU/mL and ≥ 100 mIU/mL. A decrease in the specificity of the anti-HBs ELISA had been observed in some studies for low levels of anti-HBs antibodies (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

Measure	Engerix-B Kinder Group n=287 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above the Protocol Specified Cut-off Values After Previous Vaccination With Infanrix Hexa Vaccine Anti-HBs antibody ≥ 6.2 mIU/mL	225 Participants
Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above the Protocol Specified Cut-off Values After Previous Vaccination With Infanrix Hexa Vaccine Anti-HBs antibody ≥ 10 mIU/mL	207 Participants
Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above the Protocol Specified Cut-off Values After Previous Vaccination With Infanrix Hexa Vaccine Anti-HBs antibody between ≥ 10 and < 100 mIU/mL	118 Participants
Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above the Protocol Specified Cut-off Values After Previous Vaccination With Infanrix Hexa Vaccine Anti-HBs antibody ≥ 100 mIU/mL	89 Participants

SECONDARY outcome

Timeframe: One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine

Population: Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who had received a challenge dose of Engerix-B Kinder vaccine and for whom immunogenicity data were available at the post- Engerix-B Kinder challenge time point.

Anti-HBs antibody concentrations cut-off values assessed were ≥ 6.2 mIU/mL (previously 3.3 mIU/mL) and ≥ 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA had been observed in some studies for low levels of anti-HBs antibodies (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

Measure	Engerix-B Kinder Group n=262 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Protocol Specified Cut-off Values Anti-HBs antibody ≥ 10 mIU/mL	259 Participants
Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Protocol Specified Cut-off Values Anti-HBs antibody ≥ 6.2 mIU/mL	259 Participants

SECONDARY outcome

Timeframe: One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine

Population: Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who had received a challenge dose of Engerix-B Kinder vaccine and for whom immunogenicity data were available at the post- Engerix-B Kinder challenge time point.

Antibody concentrations are expressed as Geometric mean antibody concentrations (GMCs) in mIU/mL. A decrease in the specificity of the anti-HBs 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

Measure	Engerix-B Kinder Group n=282 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Anti-HBs Antibody Concentrations	4819.1 mIU/mL Interval 3749.7 to 6193.6

SECONDARY outcome

Timeframe: After Engerix-B Kinder challenge dose (Month 1)

Population: Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who had received a challenge dose of Engerix-B Kinder vaccine and for whom immunogenicity data were available at the post- Engerix-B Kinder challenge time point.

The anamnestic response is defined as an antibody concentration ≥ 10 mIU/mL at post Engerix-B Kinder challenge dose time point for initially seronegative subjects ,and as an antibody concentration at post Engerix-B Kinder challenge dose time point ≥ 4 fold the pre-vaccination antibody concentration for initially seropositive subjects. A seropositive/seronegative subject was defined as subject with HBs antibody concentration below/greater than or equal to the seropositivity cut-off of 6.2 mIU/mL. A decrease in the specificity of the anti-HBs 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

Measure	Engerix-B Kinder Group n=262 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Number of Subjects Demonstrating an Anamnestic Response to the Engerix-B Kinder Challenge Dose	253 Participants

SECONDARY outcome

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

Population: Analysis was performed on Total Vaccinated cohort which included all subjects who received the challenge dose of Engerix-B Kinder vaccine .

Solicited local symptoms assessed were pain, redness and swelling. Any was occurrence of any local symptom regardless of their intensity grade. Grade 3 pain was considerable pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was > 50 millimeter (mm).

Outcome measures

Measure	Engerix-B Kinder Group n=297 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) Any pain	91 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) Grade 3 pain	2 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) Any redness	84 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) Grade 3 redness	0 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) Any swelling	49 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) Grade 3 swelling	0 Participants

SECONDARY outcome

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

Population: Analysis was performed on Total Vaccinated cohort which included all subjects who received the challenge dose of Engerix-B Kinder vaccine.

Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and temeperature.

Any temperature was defined as axillary temperature ≥ 37.5 degree centigrade (°C), grade 3 temperature was axillary temperature > 39.0°C. For other symptoms, any was defined as occurrence of any general symptom regardless of intensity grade or relation to vaccination and grade 3 was defined as a general symptom that prevented normal activity. Related was a general symptom assessed by the investigator as causally related to the study vaccination.

Outcome measures

Measure	Engerix-B Kinder Group n=297 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Related headache	15 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Any temperature	14 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Any fatigue	37 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Grade 3 fatigue	1 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Related fatigue	21 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Any gastrointestinal symptoms	27 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Grade 3 gastrointestinal symptoms	5 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Related gastrointestinal symptoms	5 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Any headache	36 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Grade 3 headache	2 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Grade 3 temperature	0 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs Related temperature	11 Participants

SECONDARY outcome

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

Population: Analysis was performed on Total Vaccinated cohort which included all subjects who received the challenge dose of Engerix-B Kinder vaccine.

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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.

Outcome measures

Measure	Engerix-B Kinder Group n=297 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Number of Subjects Reporting Any Unsolicited AEs	42 Participants

SECONDARY outcome

Timeframe: After the challenge dose of Engerix-B Kinder vaccine up to the study end (Day 0 to Month 1)

Population: Analysis was performed on Total Vaccinated cohort which included all subjects who received the challenge dose of Engerix-B Kinder vaccine.

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. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination.

Outcome measures

Measure	Engerix-B Kinder Group n=297 Participants Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Number of Subjects Reporting Any Serious Adverse Events (SAEs)	2 Participants

Adverse Events

Engerix-B Kinder Group

Serious events: 2 serious events

Other events: 164 other events

Deaths: 0 deaths

Serious adverse events

Measure	Engerix-B Kinder Group n=297 participants at risk Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
Immune system disorders Hypersensitivity	0.34% 1/297 • Serious adverse events were assessed from Day 0 to Month 1. Systematically assessed frequent adverse events were assessed during the 4-day post vaccination period.
Infections and infestations Lyme disease	0.34% 1/297 • Serious adverse events were assessed from Day 0 to Month 1. Systematically assessed frequent adverse events were assessed during the 4-day post vaccination period.
Nervous system disorders VIIth nerve paralysis	0.34% 1/297 • Serious adverse events were assessed from Day 0 to Month 1. Systematically assessed frequent adverse events were assessed during the 4-day post vaccination period.

Other adverse events

Measure	Engerix-B Kinder Group n=297 participants at risk Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age.
General disorders Pain	30.6% 91/297 • Serious adverse events were assessed from Day 0 to Month 1. Systematically assessed frequent adverse events were assessed during the 4-day post vaccination period.
General disorders Redness	28.3% 84/297 • Serious adverse events were assessed from Day 0 to Month 1. Systematically assessed frequent adverse events were assessed during the 4-day post vaccination period.
General disorders Swelling	16.5% 49/297 • Serious adverse events were assessed from Day 0 to Month 1. Systematically assessed frequent adverse events were assessed during the 4-day post vaccination period.
General disorders Fatigue	12.5% 37/297 • Serious adverse events were assessed from Day 0 to Month 1. Systematically assessed frequent adverse events were assessed during the 4-day post vaccination period.
General disorders Gastrointestinal symptoms	9.1% 27/297 • Serious adverse events were assessed from Day 0 to Month 1. Systematically assessed frequent adverse events were assessed during the 4-day post vaccination period.
General disorders Headache	12.1% 36/297 • Serious adverse events were assessed from Day 0 to Month 1. Systematically assessed frequent adverse events were assessed during the 4-day post vaccination period.

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