E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients under immunosuppressant therapy with past hepatitis B infection (HBsAg -/antiHBc +) but low antiHBs titers. |
Pacientes bajo tratamiento inmunosupresor con infección curada por el virus de la hepatitis B (HBsAg -/antiHBc +) pero con títulos bajo de antiHBs. |
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E.1.1.1 | Medical condition in easily understood language |
Patients under immunosuppressant therapy with past hepatitis B infection (HBsAg -/antiHBc +) but low antiHBs antibodies. |
Pacientes bajo tratamiento inmunosupresor con infección curada por el virus de la hepatitis B (HBsAg -/antiHBc +) pero con títulos bajo de anticuerpos contra la infección. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058827 |
E.1.2 | Term | Hepatitis B reactivation |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050542 |
E.1.2 | Term | Hepatitis B surface antigen negative |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052328 |
E.1.2 | Term | Hepatitis B core antigen positive |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068384 |
E.1.2 | Term | Hepatitis immunization |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1) To evaluate the immunogenicity and efficacy of the vaccine against hepatitis B in immunosuppressed patients with past hepatitis B (HBsAg negative / positive antiHBc / undetectable HBV DNA) and antiHBs titles below 100 mIU/mL, according to two groups: - Titles antiHBs <10 mIU / mL - Titles antiHBs 10-100 mIU / mL 2) To estimate the risk of reactivation of immunosuppressed patients with past HBV infection and antiHBs titers below 100 mIU/mL. |
1) Valorar la inmunogenicidad y eficacia de la vacuna contra el VHB en pacientes inmunosuprimidos con infección resuelta (HBsAg negativo/antiHBc positivo/DNA VHB indetectable) y títulos inferiores a 100 mUI/mL, según dos grupos: - Títulos antiHBs <10 mUI/mL - Títulos antiHBs 10-100 mUI/mL 2) Estimar el riesgo de reactivación de los pacientes con infección curada por VHB y títulos inferiores a 100 mUI/mL cuando se someten a tratamiento inmunosupresor, libre de terapia biológica con anticuerpos monoclonales anti-CD20. |
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E.2.2 | Secondary objectives of the trial |
Comparison of risk of Hepatitis B reactivation of immunosuppressed patients with past HBV infection who have received vaccination in contrast with a non-vaccinated control group, stratified by baseline antiHBs titers (<10 mIU / mL vs 10-100 mIU / mL) and type of therapy immunosuppressive (conventional immunosuppressant therapy vs monoclonal antibodies). HBV reactivation will be defined as the presence of detectable HBV DNA or seroreversion surface antigen (HBsAg positive). |
Comparación del riesgo de reactivación de los pacientes inmunosuprimidos con infección resuelta por VHB que han recibido vacunación en contraste con lo que no, estraficados por los títulos basales de antiHBs (<10 mUI/mL vs 10-100 mUI/mL) y tipo de terapia inmunosupresora (anticuerpos monoclonales vs inmunosupresión convencional). La reactivación del VHB se definirá como presencia de DNA VHB detectable ó seroreversión del antígeno de superficie (HBsAg positivo). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Age > 18 year-old. 2) Immunosuppressive therapy (corticosteroids, anticalcineurin, antagonists purines, mTOR inhibitors, monoclonal antibodies). 3) Past hepatitis B (HBsAg negative / positive antiHBc / undetectable HBV DNA) with anti-HBs titers below 100 mIU/mL. 4) At the time of inclusion, the patient will grant consent to participate in the study. 5) No exclusion criteria. |
1) Mayores de 18 años. 2) Tratamiento inmunosupresor (corticoides, anticalcineurínicos, antagonistas de las purinas, inhibidores mTOR, anticuerpos monoclonales). 3) Serología compatible con infección resuelta por VHB (HBsAg negativo/antiHBc positivo/DNA VHB indetectable) y títulos de antiHBs inferiores a 100 mUI/mL.. 4) Adecuadamente informados (Anexo II) otorguen su consentimiento por escrito (Anexo III) para participar en el estudio y someterse a las pruebas y exploraciones que ello comporta. En el momento de inclusión, el paciente otorgará el consentimiento para participar en el estudio. 5) Ausencia de los criterios de exclusión citados a continuación. |
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E.4 | Principal exclusion criteria |
1) Life expectancy of less than 6 months. 2) The following patients will be excluded due to the high risk of reactivation and the need for prophylactic treatment : - AntiCD-20 monoclonal antibody (Rituximab, Ofatumumab). - Chemotherapy. - Transplanted hematopoietic progenitors. 3) Patients with allergy to any component of the vaccine. 4) Patients who have previously received HBV vaccination. 5) Patients with occult hepatitis B (HBsAg negative / antiHBc positive /detectable HBV DNA ). 6) Patients on renal replacement therapy with dialysis. |
1) Enfermedad terminal, con una esperanza de vida esperada inferior a 6 meses. 2) Dado el elevado riesgo de reactivación y la necesidad de tratamiento profiláctico los siguientes pacientes serán excluídos: - Anticuerpos monoclonales antiCD-20 (Rituximab, Ofatumumab). - Quimioterapia. - Trasplantados de progenitores hematopoyéticos. 3) Pacientes alérgicos a algún componente de la vacuna. 4) Pacientes que ya hayan recibido previamente vacunación contra el VHB. 5) Pacientes con infección oculta B (HBsAg negativo/antiHBc positivo/DNA VHB detectable). 6) Pacientes bajo terapia sustitutiva renal con diálisis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Development of antiHBs titers > 100 mIU/mL after vaccination of immunosuppressed patients with past HBV infection (HBsAg - / antiHBc + /undetectable HBV DNA) and baseline low antiHBs titers. 2) Incidence of hepatitsi B reactivation in immunosuppressed patients with past HBV infection. |
1) Desarrollo de tíulos de antiHBs > 100 mUI/mL tras vacunación de los pacientes inmunosuprimidos con infección resuelta por VHB (HBsAg -/antiHBc +/DNA VHB indetectable) con niveles bajos de antiHBs. 2) Cálculo de la incidencia de reactivación del virus de la hepatitis B en pacientes inmunosuprimidos con infección curada por el VHB. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) 1 month after the administration of the last dose of HBV vaccine. 2) Follow-up during 2 years. |
1) 1 mes después de la administración de la última dosis de la vacuna. 2) Seguimiento de 2 años. |
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E.5.2 | Secondary end point(s) |
To contrast the incidence of hepatitis B reactivation in immunosuppresed patients with past hepatitis B who received vaccination in order to increase the antiHBs titers, in comparison with a non-vaccinated control group. |
Comparar la incidencia de casos de reactivación del VHB en pacientes inmunosuprimidos con infección curada por el VHB que reciban vacuna para aumentar los títulos de antiHBs, en comparación con un grupo control no vacunado. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity |
Inmunogenicidad |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Sin intervención |
No intervention |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS |
Última visita de control del último paciente incluído en el estudio. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |