Trial Outcomes & Findings for Evaluation of the Long-term Persistence of Immunity to Hepatitis B, in Adolescents Vaccinated in Infancy With Engerix™-B Kinder (NCT NCT01847430)

NCT ID: NCT01847430

Last Updated: 2018-08-20

Results Overview

The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 303 participants
• Primary outcome timeframe: One month after the challenge dose (Month 1)
• Results posted on: 2018-08-20

Participant Flow

One subject from the total number of 303 subjects enrolled did not qualify to start the study due to a protocol violation.

Participant milestones

Measure	HBV Group Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Study STARTED	302
Overall Study COMPLETED	302
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation of the Long-term Persistence of Immunity to Hepatitis B, in Adolescents Vaccinated in Infancy With Engerix™-B Kinder

Baseline characteristics by cohort

Measure	HBV Group n=302 Participants Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Age, Continuous	15.3 Years STANDARD_DEVIATION 0.5 • n=93 Participants
Sex: Female, Male Female	139 Participants n=93 Participants
Sex: Female, Male Male	163 Participants n=93 Participants

PRIMARY outcome

Timeframe: One month after the challenge dose (Month 1)

Population: The analysis was performed on the according-to-protocol (ATP) cohort of immunogenicity on all evaluable subjects who had received a challenge dose of HBV and for whom data concerning immunogenicity outcome measures were available at the time point after the HBV challenge dose.

The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL).

Outcome measures

Measure	HBV Group n=292 Participants Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value.	265 Participants

SECONDARY outcome

Timeframe: Before (Day 0) and one month after the challenge dose (Month 1)

Population: The analysis was performed on the according-to-protocol (ATP) cohort of immunogenicity on all evaluable subjects who had received a challenge dose of HBV and for whom data concerning immunogenicity outcome measures were available at the time point after the HBV challenge dose.

The cut-off values defined were ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL.

Outcome measures

Measure	HBV Group n=292 Participants Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. Day 0 (≥ 6.2 mI/mL)	208 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. Month 1 (≥ 6.2 mI/mL)	287 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. Day 0 (≥ 10 mIU/mL)	191 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. Month 1 (≥ 10 mIU/mL)	286 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. Day 0 (≥ 100 mIU/mL)	68 Participants
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. Month 1 (≥ 100 mIU/mL)	265 Participants

SECONDARY outcome

Timeframe: Before (Day 0) and one month (Month 1) after the challenge dose

Population: The analysis was performed on the according-to-protocol (ATP) cohort of immunogenicity on all evaluable subjects who had received a challenge dose of HBV and for whom data concerning immunogenicity outcome measures were available at the time point after the HBV challenge dose.

Antibody titers were summarized by geometric mean concentrations (GMCs) with their 95% CIs.

Outcome measures

Measure	HBV Group n=292 Participants Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Antibody Titers Against Hepatitis B Virus Day 0	26.5 mIU/mL Interval 21.4 to 32.8
Antibody Titers Against Hepatitis B Virus Month 1	4134.9 mIU/mL Interval 3114.2 to 5490.1

SECONDARY outcome

Timeframe: Prior to vaccination with the challenge dose

Population: The analysis was performed on the according-to-protocol (ATP) cohort of immunogenicity on all evaluable subjects who had received a challenge dose of HBV and for whom data concerning immunogenicity outcome measures were available at the time point after the HBV challenge dose.

Anamnestic response to the challenge dose was defined as:

At least (i.e. greater than or equal to ) 4-fold rise in post-vaccination anti-HBs antibody concentrations in subjects seropositive at the pre-vaccination time point Post-vaccination anti-HB antibody concentrations ≥10 mIU/mL in subjects seronegative at the pre-vaccination time point

Outcome measures

Measure	HBV Group n=291 Participants Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status. Day 0 < 6.2 mIU/mL	78 Participants
Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status. Day 0 ≥ 6.2 mIU/mL	204 Participants
Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status. Total	282 Participants

SECONDARY outcome

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

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

Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was greater than 50 millimeters (mm) i.e. >50 mm.

Outcome measures

Measure	HBV Group n=302 Participants Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. Any Pain	81 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. Grade 3 Pain	1 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. Any Redness	48 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. Grade 3 Redness	0 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. Any Swelling	16 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. Grade 3 Swelling	0 Participants

SECONDARY outcome

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

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

Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever [axillary temperature above 37.5 degrees Celsius (°C)]. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C

Outcome measures

Measure	HBV Group n=302 Participants Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Any Fatigue	84 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Fatigue	8 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Related Fatigue	47 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Any Gastrointestinal symptoms	41 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Gastrointestinal symptoms	1 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Related Gastrointestinal symptoms	21 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Any Headache	67 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Headache	4 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Related Headache	41 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Any Fever (≥ 37.5°C)	7 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Fever (> 39.0°C)	0 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Related Fever	4 Participants

SECONDARY outcome

Timeframe: During the 31-day (Days 0-30) follow-up period after the challenge dose

Population: Analysis was performed on the Total Vaccinated cohort which included all subjects who received the challenge dose of HBV 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	HBV Group n=302 Participants Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Number of Subjects Reporting Unsolicited Adverse Events (AEs).	46 Participants

SECONDARY outcome

Timeframe: During the entire study period (Day 0 to Month 1)

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

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

Outcome measures

Measure	HBV Group n=302 Participants Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Number of Subjects Reporting Any Serious Adverse Events (SAEs).	2 Participants

Adverse Events

HBV Group

Serious events: 2 serious events

Other events: 169 other events

Deaths: 0 deaths

Serious adverse events

Measure	HBV Group n=302 participants at risk Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Musculoskeletal and connective tissue disorders Arthralgia	0.33% 1/302 • Serious Adverse Events: During the entire study period (Day 0 to Month 1), Solicited local and general symptoms: During the 4-day (Days 0-3) follow-up period after the HBV challenge dose.
Injury, poisoning and procedural complications Lower limb fracture	0.33% 1/302 • Serious Adverse Events: During the entire study period (Day 0 to Month 1), Solicited local and general symptoms: During the 4-day (Days 0-3) follow-up period after the HBV challenge dose.

Other adverse events

Measure	HBV Group n=302 participants at risk Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
General disorders Pain	26.8% 81/302 • Serious Adverse Events: During the entire study period (Day 0 to Month 1), Solicited local and general symptoms: During the 4-day (Days 0-3) follow-up period after the HBV challenge dose.
General disorders Swelling	5.3% 16/302 • Serious Adverse Events: During the entire study period (Day 0 to Month 1), Solicited local and general symptoms: During the 4-day (Days 0-3) follow-up period after the HBV challenge dose.
General disorders Fatigue	27.8% 84/302 • Serious Adverse Events: During the entire study period (Day 0 to Month 1), Solicited local and general symptoms: During the 4-day (Days 0-3) follow-up period after the HBV challenge dose.
Gastrointestinal disorders Gastrointestinal symptoms	13.6% 41/302 • Serious Adverse Events: During the entire study period (Day 0 to Month 1), Solicited local and general symptoms: During the 4-day (Days 0-3) follow-up period after the HBV challenge dose.
Nervous system disorders Headache	22.2% 67/302 • Serious Adverse Events: During the entire study period (Day 0 to Month 1), Solicited local and general symptoms: During the 4-day (Days 0-3) follow-up period after the HBV challenge dose.
General disorders Redness	15.9% 48/302 • Serious Adverse Events: During the entire study period (Day 0 to Month 1), Solicited local and general symptoms: During the 4-day (Days 0-3) follow-up period after the HBV challenge dose.

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