E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autoimmune Hepatitis (AIH) |
Hepatitis Autoinmunitaria (HAI) |
|
E.1.1.1 | Medical condition in easily understood language |
Autoimmune hepatitis is a disease where your immune system attacks your own liver |
La hepatitis autoinmunitaria es una enfermedad donde su sistema inmune ataca su propio hígado |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003827 |
E.1.2 | Term | Autoimmune hepatitis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of the study is 2-fold: Part 1 - To evaluate whether VAY736 is superior to placebo on alanine aminotransferase (ALT) at Week 24, in patients with AIH who are incomplete responders (i.e. did not achieve normalization of ALT) or intolerant to standard therapy.
Part 2 - To confirm the efficacy (biochemical and histological remission) and safety of the dose determined from Part 1 in this population. |
El propósito del estudio es doble: Parte 1 - Evaluar si VAY736 es superior a placebo con respecto a la alanino aminotransferasa (ALT) en la semana 24, en pacientes con HAI que sean respondedores incompletos (es decir, que no hayan alcanzado la normalización de ALT) o intolerantes al tratamiento estándar. Parte 2 - Confirmar la eficacia (remisión bioquímica e histológica) y seguridad de la dosis determinada en la parte 1 en esta población |
|
E.2.2 | Secondary objectives of the trial |
Part 1 aims to evaluate the dose-response relationship of VAY736 with respect to normalization in ALT at Week 24.
Other protocol-defined secondary objectives may apply |
Parte 1 - Evaluar la relación dosis-respuesta de VAY736 respecto a la normalización de ALT en la semana 24.
Pueden aplicarse otros objetivos secundarios definidos por el protocolo |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- AIH diagnosed per International Autoimmune Hepatitis Group - Liver biopsy with Ishak modified HAI indicating active AIH - Incomplete response to OR intolerance of standard therapy (per AASLD)
Other protocol-defined inclusion criteria may apply |
-HAI diagnosticada de acuerdo con los criterios de diagnóstico del International Autoimmune Hepatitis Group (IAIHG) -Biopsia hepática con Ishak modificado que indica HAI active - Respuesta incompleta o intolerancia al tratamiento estándar (según las guías de la AASLD)
Pueden aplicarse otros criterios de inclusión definidos por el protocolo |
|
E.4 | Principal exclusion criteria |
- Prior use of any B-cell depleting therapy - Required regular use of medications with known hepatotoxicity - Decompensated cirrhosis - Diagnosis of overlap syndrome with AIH (e.g., AIH+PBC, AIH+PSC) - Drug related AIH at screening or a history of drug related AIH - History of drug abuse or unhealthy alcohol use - History of malignancy of any organ system - Pregnant or nursing (lactating) women - Other protocol-defined exclusion criteria may apply |
-El uso previo de algún tratamiento depletivo de células B previo -Necesidad de uso periódico de medicación con hepatotoxicidad conocida - Cirrosis descompensada - Diagnóstico de síndrome de superposición con la hepatitis autoinmunitaria (p. ej., HAI+CBP, HAI+CEP). - HAI relacionada con fármacos en la selección o antecedentes de HAI relacionada con fármacos. - Antecedentes de abuso de drogas o consumo nocivo de alcohol - Historial de malignidad de cualquier sistema de órganos - Mujeres embarazadas o en periodo de lactancia - Pueden aplicarse otros criterios de exclusión definidos por el protocolo |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: ALT normalization |
Parte 1: normalización de ALT |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Part 1: ALT normalization by dose |
Part1: normalización ALT por dosis |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Czech Republic |
Denmark |
Germany |
Japan |
Netherlands |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The study will complete when the last subject completes their Study Completion visit, and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator. |
El estudio se completará cuando el último sujeto complete su visita de finalización del estudio, y todas las evaluaciones repetidas asociadas a esta visita deben ser documentadas y seguidas apropiadamente por el investigador. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |