Evaluation of Antibody Persistence & Immune Memory in Subjects Vaccinated During Adolescence With Twinrix™
18 juillet 2018 mis à jour par: GlaxoSmithKline
An Open Multicentre, Multicountry Study to Evaluate Long-term Antibody Persistence and Immune Memory Between Years 11 and 15 After the Primary Study HAB-084 in Which Healthy Adolescents Were Vaccinated With Twinrix™ Adult Following a Two-dose Schedule or Twinrix™ Junior Following a Three-dose Schedule.
This study will evaluate the immune response against Hepatitis-A (HAV) and Hepatitis B surface (HBs) antigen in healthy subjects aged 12 to 15 years (at the time of primary vaccination), who received vaccination course with GSK Biologicals' Twinrix Adult and Twinrix Junior vaccine, approximately 10 years ago in the primary study. The subjects will be invited for blood sampling at 11, 12, 13, 14 and 15 years after primary vaccination to evaluate the persistence of immune response. For subjects detected with decreased immunity, the presence of immune memory against hepatitis A & B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine 6 to 12 months after the Year 15 follow-up time-point.
No new subjects will be recruited during this booster phase of the study.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
210
Phase
- Phase 4
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
12 ans à 15 ans (Enfant)
Accepte les volontaires sains
Oui
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
- A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study
- Written informed consent obtained from the subject.
All subjects must satisfy the following criteria at entry into the challenge dose phase:
- A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study.
- Subjects who participated in the long-term follow-up phase of the primary study and for whom the antibody concentrations were below specified value for anti-HAV antibodies and/ or for anti-HBs antibodies at the last available follow-up time-points.
- Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
- Written informed consent obtained from the subject.
- Healthy subjects as established by medical history and clinical examination before entering into the challenge dose phase of this study.
- If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination.
Exclusion Criteria:
The following criteria should be checked at each follow-up visit. If any apply at study entry, the subject must not be included at that long-term follow-up visit.
- Use of any investigational or non-registered product (drug or vaccine) since the last blood sampling visit.
- Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine since the primary vaccination course of the primary study.
- History of hepatitis A or hepatitis B infection.
- Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within 3 months prior to blood sampling.
The following criteria should be checked before the challenge dose phase. If any apply, the subject must not be included in the challenge dose phase:
- Use of any investigational or non-registered product (drug or vaccine) within 30 days before the administration of the challenge dose or planned use during the study period outside the context of the study.
- Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine between the primary vaccination course of the primary study and the challenge dose visit.
- History of hepatitis A or hepatitis B infection.
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
- Acute disease at the time of.
- Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the challenge dose or planned administration before the final blood sampling point (one month after the challenge dose).
- Pregnant or lactating female.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Twinrix Adult Group
Subjects received 2 doses of Twinrix™ Adult intramuscularly according to a 0, 6 month schedule in the primary study
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Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.
If a subject became seronegative for anti-HAV antibodies (< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.
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Expérimental: Twinrix Junior Group
Subjects received 3 doses of Twinrix™ Junior (= half dose Twinrix™ Adult) intramuscularly according to a 0, 1, 6 month schedule in the primary study
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Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.
If a subject became seronegative for anti-HAV antibodies (< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Anti-HAV Antibody Concentrations
Délai: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084
|
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.
The analysis was performed on anti-HAV seropositive subjects.
Seropositive subjects are subjects with anti-HAV antibody concentrations >= 15 mIU/mL.
|
At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084
|
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Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values
Délai: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084
|
Anti-HBs antibody cut-off values assessed were >= 6.2 mIU/mL and >= 10 mIU/mL.
Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL).
The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by ChemiLuminescence ImmunoAssay (CLIA).
|
At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084
|
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Anti-HBs Antibody Concentrations
Délai: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084.
|
Antibodys concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations >= 6.2 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by CLIA. |
At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084.
|
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Anti-HBs Anamnestic Response.
Délai: One month after the challenge dose.
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Anamnestic response was defined as: Anti-HBs antibody concentrations ≥ 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time-points. At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time-points. |
One month after the challenge dose.
|
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Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value.
Délai: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084.
|
Anti-HAV antibody cut-off value assessed was >= 15 milli-International Units per milliliter (mIU/mL).
|
At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084.
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
Délai: Since the last long-term follow-up visit up to Year 11.
|
SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
|
Since the last long-term follow-up visit up to Year 11.
|
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Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
Délai: Since the last long-term follow-up visit up to Year 12.
|
SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
|
Since the last long-term follow-up visit up to Year 12.
|
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Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
Délai: Since the last long-term follow-up visit up to Year 13.
|
SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
|
Since the last long-term follow-up visit up to Year 13.
|
|
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
Délai: Since the last long-term follow-up visit up to Year 14.
|
SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
|
Since the last long-term follow-up visit up to Year 14.
|
|
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
Délai: Since the last long-term follow-up visit up to Year 15.
|
SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
|
Since the last long-term follow-up visit up to Year 15.
|
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Number of Subjects With Anti-hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-off Value.
Délai: Before (PRE) the challenge dose
|
Anti-HAV antibody cut-off value assessed was >= 15 milli-International Units per milliliter (mIU/mL). Note: Since none of the subjects were seronegative for anti-HAV antibody concentration at the pre-challenge time point, subjects received only the HBV vaccine as the challenge dose. |
Before (PRE) the challenge dose
|
|
Anti-HAV Antibody Concentrations
Délai: Before (PRE) the challenge dose
|
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.
The analysis was performed on anti-HAV seropositive subjects.
Seropositive subjects are subjects with anti-HAV antibody concentrations >= 15 mIU/mL.
|
Before (PRE) the challenge dose
|
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Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events.
Délai: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose
|
Solicited local symptoms assessed were pain, redness and swelling.
Any = occurrence of the symptom regardless of intensity grade.
Grade 3 pain = pain that prevented normal activity.
Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.
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During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose
|
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Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values
Délai: Before (PRE) and one month after (POST) the challenge dose
|
Anti-HBs antibody cut-off values assessed were >= 6.2 mIU/mL and >= 10 mIU/mL
|
Before (PRE) and one month after (POST) the challenge dose
|
|
Anti-HBs Antibody Concentrations
Délai: Before (PRE) and one month after (POST) the challenge dose
|
Antibody concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL.
The analysis was performed on anti-HBs seropositive subjects.
Seropositive subjects are subjects with anti-HBs antibody concentrations >= 6.2 mIU/mL.
|
Before (PRE) and one month after (POST) the challenge dose
|
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Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
Délai: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose.
|
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever (axillary temperature).
Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain.
Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination.
Grade 3 symptoms = symptoms that prevented normal activity.
Grade 3 fever = axillary temperature > 39.5°C.
Related = general symptoms which were assessed by the investigator as causally related to vaccination.
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During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose.
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Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms.
Délai: During the 31-day (Day 0 to 30) follow-up period after the challenge dose.
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An unsolicited AE covers 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.
Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study.
Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Grade 3 = AE that prevented normal activity.
Related = AE assessed by the investigator as causally related to the study vaccination.
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During the 31-day (Day 0 to 30) follow-up period after the challenge dose.
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Number of Subjects With Serious Adverse Events (SAEs).
Délai: One month after the administration of the challenge dose (Month 0 to Month 1)
|
Serious adverse events (SAEs) assessed included medical occurrences that resulted in death, were 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.
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One month after the administration of the challenge dose (Month 0 to Month 1)
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Agrawal A, Kolhapure S, Andani A, Ota MOC, Badur S, Karkada N, Mitra M. Long-Term Persistence of Antibody Response with Two Doses of Inactivated Hepatitis A Vaccine in Children. Infect Dis Ther. 2020 Dec;9(4):785-796. doi: 10.1007/s40121-020-00311-8. Epub 2020 Jul 24.
- Beran J, Van Der Meeren O, Leyssen M, D'silva P. Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine. Vaccine. 2016 May 23;34(24):2686-91. doi: 10.1016/j.vaccine.2016.04.033. Epub 2016 Apr 20.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 mai 2009
Achèvement primaire (Réel)
1 juillet 2014
Achèvement de l'étude (Réel)
1 juillet 2014
Dates d'inscription aux études
Première soumission
2 avril 2009
Première soumission répondant aux critères de contrôle qualité
2 avril 2009
Première publication (Estimation)
3 avril 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
20 août 2018
Dernière mise à jour soumise répondant aux critères de contrôle qualité
18 juillet 2018
Dernière vérification
1 juillet 2018
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système digestif
- Infections par virus à ARN
- Maladies virales
- Infections
- Infections transmissibles par le sang
- Maladies transmissibles
- Maladies du foie
- Hépatite, virale, humaine
- Infections à Hépadnaviridae
- Infections par le virus de l'ADN
- Infections à entérovirus
- Infections à Picornaviridae
- Hépatite B
- Hépatite
- Hépatite A
Autres numéros d'identification d'étude
- 110699
- 110700 (Autre identifiant: GSK)
- 110701 (Autre identifiant: GSK)
- 110702 (Autre identifiant: GSK)
- 110703 (Autre identifiant: GSK)
- 110704 (Autre identifiant: GSK)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
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Description du régime IPD
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Données/documents d'étude
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Protocole d'étude
Identifiant des informations: 110699Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
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Ensemble de données de participant individuel
Identifiant des informations: 110699Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
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Rapport d'étude clinique
Identifiant des informations: 110699Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
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Spécification du jeu de données
Identifiant des informations: 110699Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
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Formulaire de consentement éclairé
Identifiant des informations: 110699Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .