Trial Outcomes & Findings for Long-Term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,1,6 Month Schedule (NCT NCT00289718)

NCT ID: NCT00289718

Last Updated: 2018-02-15

Results Overview

Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 51 participants
• Primary outcome timeframe: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination
• Results posted on: 2018-02-15

Participant Flow

Participant milestones

Measure	Twinrix Group Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up
Overall Study STARTED	51
Overall Study COMPLETED	51
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Long-Term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,1,6 Month Schedule

Baseline characteristics by cohort

Measure	Twinrix Group n=51 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up
Age, Continuous	36.4 years STANDARD_DEVIATION 5.65 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-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).

Outcome measures

Measure	Twinrix Group n=33 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 11 (N=33)	369.1 mIU/mL Interval 273.8 to 497.7	—
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 12 (N=33)	323.5 mIU/mL Interval 233.8 to 447.7	—
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 13 (N=32)	293.7 mIU/mL Interval 214.8 to 401.8	—
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 14 (N=30)	298.2 mIU/mL Interval 217.0 to 409.6	—
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration Year 15 (N=29)	274.4 mIU/mL Interval 200.9 to 374.7	—

PRIMARY outcome

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

Population: Analysis was performed on the Long Term Total cohort, on subjects who received an additional vaccine dose. Only 1 subject received an additional dose.

Solicited local symptoms assessed include pain, redness and swelling. Any was defined as occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain was defined as pain that prevented normal everyday activities. Grade 3 swelling was greater than 100 millimeters (mm) i.e. >100mm.

Outcome measures

Measure	Twinrix Group n=1 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. Pain	1 subjects	—
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. Redness	0 subjects	—
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. Swelling	0 subjects	—

PRIMARY outcome

Timeframe: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-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

A seropositive subject was defined as a vaccinated subject who had a anti-HAV antibody titres ≥ 33 mIU/ml.

Outcome measures

Measure	Twinrix Group n=33 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Number of Subjects Seropositive for Anti-HAV Antibodies Year 11 (N=33)	33 Subjects	—
Number of Subjects Seropositive for Anti-HAV Antibodies Year 12 (N=33)	33 Subjects	—
Number of Subjects Seropositive for Anti-HAV Antibodies Year 13 (N=32)	32 Subjects	—
Number of Subjects Seropositive for Anti-HAV Antibodies Year 14 (N=30)	30 Subjects	—
Number of Subjects Seropositive for Anti-HAV Antibodies Year 15 (N=29)	29 Subjects	—

PRIMARY outcome

Timeframe: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-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 GMC expressed as mIU/mL. NOTE: There was a change of assay kit at Year 15 time-point, thus for the sake of bridging, blood samples corresponding to Year 14 were re-tested with ChemiLuminescence ImmunoAssay (CLIA). From Year 11 to Year 14, anti-HBs antibody concentrations were tested with ELISA with cut-off of 3.3 mIU/mL while, Year 14* onwards, anti-HBs antibody concentrations were tested with the CLIA with cut-off of 6.2 mIU/mL.

Outcome measures

Measure	Twinrix Group n=33 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Year 11 (N=33)	123.6 mIU/mL Interval 76.1 to 200.9	—
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Year 12 (N=33)	150.3 mIU/mL Interval 92.9 to 243.0	—
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Year 13 (N=32)	77.8 mIU/mL Interval 48.7 to 124.4	—
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Year 14 (N=30)	71.7 mIU/mL Interval 45.5 to 113.1	—
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Year 14* (N=28)	95.3 mIU/mL Interval 54.1 to 168.1	—
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Year 15 (N=29)	79.2 mIU/mL Interval 45.7 to 137.3	—

PRIMARY outcome

Timeframe: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-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

A seropositive subject was defined as a vaccinated subject who had anti-HB antibody titres ≥ 1 mIU/mL.

NOTE: There was a change of assay kit at Year 15 time-point, thus for the sake of bridging, blood samples corresponding to Year 14 were re-tested with ChemiLuminescence ImmunoAssay (CLIA)

Outcome measures

Measure	Twinrix Group n=33 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Number of Subjects Seropositive for Anti-HB Antibodies YEAR 11 (N=33)	33 Subjects	—
Number of Subjects Seropositive for Anti-HB Antibodies YEAR 12 (N=33)	33 Subjects	—
Number of Subjects Seropositive for Anti-HB Antibodies YEAR 13 (N=32)	32 Subjects	—
Number of Subjects Seropositive for Anti-HB Antibodies YEAR 14 (N=30)	29 Subjects	—
Number of Subjects Seropositive for Anti-HB Antibodies Year 14* (N=28)	27 Subjects	—
Number of Subjects Seropositive for Anti-HB Antibodies YEAR 15 (N=29)	28 Subjects	—

PRIMARY outcome

Timeframe: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-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

A seroprotected subject was defined as a subjects with the anti-HBs titres ≥ 10 mIU/mL.

NOTE: There was a change of assay kit at Year 15 time-point, thus for the sake of bridging, blood samples corresponding to Year 14 were re-tested with ChemiLuminescence ImmunoAssay (CLIA)

Outcome measures

Measure	Twinrix Group n=33 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Number of Subjects Seroprotected for Anti-HBs Antibodies. YEAR 15 (N=29)	28 Subjects	—
Number of Subjects Seroprotected for Anti-HBs Antibodies. YEAR 11 (N=33)	33 Subjects	—
Number of Subjects Seroprotected for Anti-HBs Antibodies. YEAR 12 (N=33)	32 Subjects	—
Number of Subjects Seroprotected for Anti-HBs Antibodies. YEAR 13 (N=32)	32 Subjects	—
Number of Subjects Seroprotected for Anti-HBs Antibodies. YEAR 14 (N=30)	29 Subjects	—
Number of Subjects Seroprotected for Anti-HBs Antibodies. Year 14* (N=28)	27 Subjects	—

PRIMARY outcome

Timeframe: During the follow-up period after additional vaccination (minimum 30 days)

Population: Analysis was performed on the Long Term Total cohort, on subjects who received an additional vaccine dose. Only 1 subject received an additional dose.

A SAE was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of 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 and related was an event assessed by the investigator as causally related to the study vaccination.

Outcome measures

Measure	Twinrix Group n=1 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) n=1 Participants Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Number of Subjects Reporting Serious Adverse Events (SAE)	0 subjects	1 subjects

PRIMARY outcome

Timeframe: Before the additional dose and 1 month after the additional dose

Population: Analysis was performed on the Long Term Total cohort, on subjects who received an additional vaccine dose. Only 1 subject received an additional dose.

Concentrations given as GMC expressed as mIU/mL. If a subject became seronegative (< 10 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose.

Outcome measures

Measure	Twinrix Group n=1 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration before additional dose at Year 12	9.7 mIU/mL	—
Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration 1 month after additional dose at Year 12	NA mIU/mL One subject identified as eligible to receive the additional dose at Year 12 was withdrawn from the LT Cohort for immunogenicity because of non-compliance with the protocol therefore, blood sample was not taken	—
Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration before additional dose at Year 13	9.5 mIU/mL	—
Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration 1 month after additional dose at Year 13	15022.3 mIU/mL	—

PRIMARY outcome

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

Population: Analysis was performed on the Long Term Total cohort, on subjects who received an additional vaccine dose. Only 1 subject received an additional dose.

Solicited general symptoms assessed included fatigue, headache, malaise, nausea, vomiting and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination.

Outcome measures

Measure	Twinrix Group n=1 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Number of Subjects Reporting Any Solicited General Symptoms. Any Fatigue	0 Subjects	—
Number of Subjects Reporting Any Solicited General Symptoms. Any Headache	0 Subjects	—
Number of Subjects Reporting Any Solicited General Symptoms. Any Malaise	0 Subjects	—
Number of Subjects Reporting Any Solicited General Symptoms. Any Nausea	0 Subjects	—
Number of Subjects Reporting Any Solicited General Symptoms. Any Vomiting	0 Subjects	—
Number of Subjects Reporting Any Solicited General Symptoms. Any Fever	0 Subjects	—

PRIMARY outcome

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

Population: Analysis was performed on the Long Term Total cohort, on subjects who received an additional vaccine dose. Only 1 subject received an additional 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.

Outcome measures

Measure	Twinrix Group n=1 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Number of Subjects Reporting Unsolicited Adverse Events (AE)	1 subjects	—

PRIMARY outcome

Timeframe: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination

Population: Analysis was performed on the LT Total Cohort that included all subjects who returned at a specified follow-up study and who belonged to the Total Cohort of the primary vaccination course.

A SAE was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of 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 and related was an event assessed by the investigator as causally related to the study vaccination.

Outcome measures

Measure	Twinrix Group n=51 Participants Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up	Twinrix Group (Lot B) Subjects who received 2 doses of Twinrix™ (lot B) in the primary study.
Number of Subjects Reporting Serious Adverse Events (SAEs)	0 Subjects	—

Adverse Events

Twinrix Group

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Twinrix Group n=1 participants at risk Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up
Musculoskeletal and connective tissue disorders Hallux valgus	100.0% 1/1 • Serious Adverse Events (SAEs):Up to Year 15 and after additional HBV vaccination;Solicited local and general symptoms:During the 4-day follow-up period post additional dose;Unsolicited AEs:During the 30-day follow-up period post additional dose. Safety results were reported for subjects who received an additional vaccine dose. Only one subject received an additional dose

Other adverse events

Measure	Twinrix Group n=1 participants at risk Subjects who received 2 doses of Twinrix™ (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 Twinrix Group for data analyses during the long term follow-up
General disorders Pain	100.0% 1/1 • Serious Adverse Events (SAEs):Up to Year 15 and after additional HBV vaccination;Solicited local and general symptoms:During the 4-day follow-up period post additional dose;Unsolicited AEs:During the 30-day follow-up period post additional dose. Safety results were reported for subjects who received an additional vaccine dose. Only one subject received an additional dose
Infections and infestations Nasopharyngitis	100.0% 1/1 • Serious Adverse Events (SAEs):Up to Year 15 and after additional HBV vaccination;Solicited local and general symptoms:During the 4-day follow-up period post additional dose;Unsolicited AEs:During the 30-day follow-up period post additional dose. Safety results were reported for subjects who received an additional vaccine dose. Only one subject received an additional 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