A Phase 3 interventional study of Twinrix™ in Hepatitis B and Hepatitis A, sponsored by GlaxoSmithKline. Completed at 1 site in Belgium. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-08-17.
Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Prevention
The aim of this study is to evaluate the long-term persistence of hepatitis A and B antibodies at Years 11, 12, 13, 14 and 15 after subjects received their first dose of a 3 dose primary vaccination schedule of combined hepatitis A/hepatitis B vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
This protocol posting deals with objectives \& outcome measures of the extension phase at Year 11-15.
This is a long-term follow-up study at Years 11, 12, 13, 14 and 15 after primary vaccination with GSK Biologicals' hepatitis A/hepatitis B vaccine (three-dose schedule with 3 different lots). To evaluate the long-term antibody persistence, volunteers will be bled at Years 11, 12, 13, 14 and 15 after the first vaccine dose of the primary vaccination course to determine their anti-HAV and anti-HBs antibody concentrations.
No additional subjects will be recruited in the course of this extension study. If a subject has become seronegative for anti-HAV antibodies or lost anti-HBs seroprotection concentrations at the long-term blood sampling time point (i.e. Years 11, 12, 13, 14 or 15), he/ she will be offered an additional vaccine dose.
2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.
This study's enrollment of 50 is below the median of 100 across 1,886 interventional studies indexed under Hepatitis A.
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Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.
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Inclusion Criteria:
Was vaccinated with Lot A in the primary study.
Biological: Twinrix™
Was vaccinated with Lot B in the primary study.
Biological: Twinrix™
Was vaccinated with Lot C in the primary study.
Biological: Twinrix™
Intramuscular injection, 3 doses
Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value
Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity.
Time frame: Years 11, 12, 13, 14 and 15
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values
Cut-off values were defined 3.3 mIU/mL for the in-house anti-HBs assay and 6.2 mIU/mL for the ChemiLuminescence ImmunoAssay, which was also considered as seropositivity, and 10 mIU/mL.
Time frame: Years 11, 12, 13, 14 and 15
Anti-HAV and Anti-HBs Antibody Concentrations
Concentrations are expressed as geometric mean concentrations (GMCs) in mIU/mL. The laboratory assay was changed from Year 13 to Year 14 to in-house ELISA and at Year 15 to CLIA for anti-HBs GMCs.Thus for the sake of bridging, blood samples corresponding to Year 14 previously tested with ELISA were re-tested with CLIA (Year 14\*).
Time frame: Years 11, 12, 13, 14 and 15
Anti-HBs Antibody Concentrations
Subjects who lost seroprotective concentrations for anti-HBs (\< 10 mIU/mL) at any of the LT follow-up timepoints received an additional dose of Engerix after year 15. Two subjects were eligible for this after Year 11. 3.29 in the table means a concentration of \< 3.3 mIU/mL. As the concentration was calculated per subject no mean concentration was calculated and also no measure of dispersion.
Time frame: at Year 11, pre-additional vaccine, after additional dose of Engerix
Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response
Anamnestic response was assessed in subjects receiving an additional vaccine dose of Engerix. Two subjects were found eligible at Year 11 for this additional vaccine dose. Anamnestic response was defined as: * post-additional vaccination anti-HBs concentration \>= 10 mIU/mL in subject seronegative before additional dose. * 4-fold increase post-additional dose compared to pre-additional vaccine time point.
Time frame: 30 days post additional dose of Engerix
Number of Subjects With Solicited Local and General Symptoms Assessed
Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, fever, gastrointestinal, headache.
Time frame: During the 4-day follow-up period after additional vaccination with Engerix
Number of Subjects With Unsolicited Symptoms
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.
Time frame: During the 30-day follow-up period after additional Engerix vaccination
Number of Subjects With Serious Adverse Events (SAEs)
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
Time frame: During the 30-day follow-up period after additional Engerix vaccination
Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy
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.
Time frame: up to Year 11, 12, 13, 14, 15
| Milestone | Twinrix Group |
|---|---|
| Started | 37 |
| Completed | 37 |
| Not completed | 0 |
| Milestone | Twinrix Group |
|---|---|
| Started | 40 |
| Completed | 40 |
| Not completed | 0 |
| Milestone | Twinrix Group |
|---|---|
| Started | 37 |
| Completed | 37 |
| Not completed | 0 |
| Milestone | Twinrix Group |
|---|---|
| Started | 43 |
| Completed | 43 |
| Not completed | 0 |
| Milestone | Twinrix Group |
|---|---|
| Started | 50 |
| Completed | 49 |
| Not completed | 1 |
| Withdrew: Withdrawal by subject | 1 |
Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity.
| Participants | Twinrix Group |
|---|---|
| Year 11 | 25 |
| Year 12 | 28 |
| Year 13 | 23 |
| Year 14 | 24 |
| Year 15 | 31 |
Cut-off values were defined 3.3 mIU/mL for the in-house anti-HBs assay and 6.2 mIU/mL for the ChemiLuminescence ImmunoAssay, which was also considered as seropositivity, and 10 mIU/mL.
| Participants | Twinrix Group |
|---|---|
| Year 11 3.3 mIU/mL | 23 |
| Year 12 3.3 mIU/mL | 25 |
| Year 13 3.3 mIU/mL | 20 |
| Year 14 3.3 mIU/mL | 21 |
| Year 14 6.2 mIU/mL | 21 |
| Year 15 6.2 mIU/mL | 28 |
| Year 11 10 mIU/mL | 23 |
| Year 12 10 mIU/mL | 25 |
| Year 13 10 mIU/mL | 20 |
| Year 14 10 mIU/mL | 21 |
| Year 15 10 mIU/mL | 28 |
Concentrations are expressed as geometric mean concentrations (GMCs) in mIU/mL. The laboratory assay was changed from Year 13 to Year 14 to in-house ELISA and at Year 15 to CLIA for anti-HBs GMCs.Thus for the sake of bridging, blood samples corresponding to Year 14 previously tested with ELISA were re-tested with CLIA (Year 14\*).
| mIU/mL | Twinrix Group |
|---|---|
| Year 11 anti-HAV | 680.3 (453.8 to 1019.9) |
| Year 12 anti-HAV | 602.7 (420.8 to 863.2) |
| Year 13 anti-HAV | 601.5 (408.7 to 885.4) |
| Year 14 anti-HAV | 524.7 (368.7 to 746.5) |
| Year 15 anti-HAV | 610.7 (443.1 to 841.6) |
| Year 11 anti-HBs | 458.9 (257.4 to 817.8) |
| Year 12 anti-HBs | 475.8 (284.4 to 795.9) |
| Year 13 anti-HBs | 163.3 (99.7 to 267.3) |
| Year 14 anti-HBs | 149.1 (94.8 to 234.5) |
| Year 14* anti-HBs | 242.8 (127.0 to 464.3) |
| Year 15 anti-HBs | 210.9 (121.5 to 366.2) |
Subjects who lost seroprotective concentrations for anti-HBs (\< 10 mIU/mL) at any of the LT follow-up timepoints received an additional dose of Engerix after year 15. Two subjects were eligible for this after Year 11. 3.29 in the table means a concentration of \< 3.3 mIU/mL. As the concentration was calculated per subject no mean concentration was calculated and also no measure of dispersion.
| mIU/mL | Twinrix Group |
|---|---|
| subject 1 Year 11 | 3.29 |
| subject 2 Year 11 | 3.29 |
| subject 1 before additional dose | 3.29 |
| subject 2 before additional dose | 14.5 |
| subject 1 after additional dose | 6548.1 |
| subject 2 after additional dose | 554.0 |
Anamnestic response was assessed in subjects receiving an additional vaccine dose of Engerix. Two subjects were found eligible at Year 11 for this additional vaccine dose. Anamnestic response was defined as: * post-additional vaccination anti-HBs concentration \>= 10 mIU/mL in subject seronegative before additional dose. * 4-fold increase post-additional dose compared to pre-additional vaccine time point.
| Participants | Twinrix Group |
|---|---|
| Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response | 2 |
Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, fever, gastrointestinal, headache.
| Participants | Twinrix Group |
|---|---|
| Pain | 0 |
| Redness | 0 |
| Swelling | 0 |
| Fatigue | 1 |
| Fever | 0 |
| Gastrointestinal | 1 |
| Headache | 0 |
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.
| Participants | Twinrix Group |
|---|---|
| Number of Subjects With Unsolicited Symptoms | 1 |
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
| Participants | Twinrix Group |
|---|---|
| Number of Subjects With Serious Adverse Events (SAEs) | 0 |
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.
| Participants | Twinrix Group |
|---|---|
| Year 11 | 0 |
| Year 12 | 0 |
| Year 13 | 0 |
| Year 14 | 0 |
| Year 15 | 0 |
Collected over SAEs were collected up to Year 15. Other adverse events were collected within 4-days after additional vaccination (solicited) and 30-days after additional vaccination (unsolicited).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Twinrix Group | — | 0/50 (0%) | 2/2 (100%) |
| Event | Twinrix Group |
|---|---|
| FatigueGeneral disorders | 1/2 |
| GastrointestinalGeneral disorders | 1/2 |
| Heaviness sensation above eyesEye disorders | 1/2 |
| Age, Continuous(Years) | Twinrix Group |
|---|---|
| Mean | 34.4 ± 2.66 |
| Sex: Female, Male(Participants) | Twinrix Group |
|---|---|
| Female | 39 |
| Male | 11 |
Plan to share: Yes — Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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