E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-alcoholic Steatohepatitis (NASH) |
Esteatohepatitis no alcohólica (EHNA) |
|
E.1.1.1 | Medical condition in easily understood language |
Fatty liver disease not related to alcohol intake |
Esteatohepatitis no alcohólica (EHNA) y fibrosis hepática |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053219 |
E.1.2 | Term | Non-alcoholic steatohepatitis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
|
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 |
The primary objective of this study is to evaluate the safety and tolerability of tropifexor + CVC in patients with NASH with fibrosis stage F2/F3 by monitoring adverse events, vital signs and laboratory values during 48 weeks of treatment as compared to monotherapy with each of tropifexor and CVC |
El objetivo principal de este estudio es evaluar la seguridad y tolerabilidad de tropifexor + CVC en pacientes con EHNA con fibrosis en estadio F2/F3 mediante la monitorización de los acontecimientos adversos, constantes vitales y valores de laboratorio durante 48 semanas de tratamiento en comparación con tropifexor y CVC en monoterapia |
|
E.2.2 | Secondary objectives of the trial |
To characterize the efficacy of different doses of the combination drug tropifexor + CVC in patients with NASH with fibrosis stage F2/F3 as assessed by histological improvement after 48 weeks of treatment compared to monotherapies (tropifexor and CVC) compared to baseline biopsy. |
Caracterizar la eficacia de diferentes dosis de la combinación de tropifexor + CVC en pacientes con EHNA con fibrosis en estadio F2/F3 según la evaluación de la mejoría histológica después de 48 semanas de tratamiento en comparación con los fármacos en monoterapia (tropifexor y CVC) y en comparación con la biopsia basal. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written informed consent must be obtained before any assessment is performed.
Male and female patients 18 years or older (at the time of the screening visit). Patients must weigh at least 50 kg (110 lb) and no more than 200 kg (440 lb) to participate in the study.
Adequate liver biopsy sample for evaluation by a central reader.
Presence of NASH as demonstrated by histologic evidence based on liver biopsy - NASH with fibrosis stage F2/F3, demonstrated on liver biopsy with evaluation by central reading during the screening period. Alternatively, a historical biopsy can be used if performed within 6 months prior to screening and evaluated by a central reader, if:
- the patient has been receiving any of the therapies listed in Table 5-4, the dose must have been stable (since 1 month before the biopsy up to and including screening) - the patient's weight has been stable (maximum weight loss of 10% since biopsy up to and including screening) |
.Obtención del consentimiento informado por escrito antes de realizar cualquier evaluación. .Pacientes de ambos sexos >/=18 años de edad (en el momento de la visita de selección) con un peso mínimo de 50 kg y máximo de 200 kg .Muestra adecuada para su interpretación a nivel central de biopsia hepática. .Presencia de EHNA demostrada mediante la histología de una biopsia hepática - EHNA con fibrosis en estadio F2/F3 demostrada en la biopsia hepática con evaluación a nivel central durante el período de selección. Alternativamente, se puede utilizar una biopsia anterior si se realizó durante los 6 meses anteriores a la selección y evaluada por un lector central, en caso de que: -El paciente haya estado recibiendo alguno de los tratamientos indicados en la Tabla 5-4, la dosis debe haber sido estable (desde el mes anterior a la biopsia hasta la selección, incluida). - El peso del paciente haya sido estable (pérdida máxima de peso del 10 % desde la biopsia hasta la selección, incluida). |
|
E.4 | Principal exclusion criteria |
Previous exposure to elafibranor, CVC, tropifexor, obeticholic acid (OCA), LMB763 or any other FXR agonist.
Participated in a clinical trial and treated with any investigational product being evaluated for the treatment of liver fibrosis or NASH in the 6 months before screening.
Patients taking medications prohibited by the protocol.
Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more than 20 g/day in females and more than 30 g/day in males, on average) and/or a score on the modified AUDIT questionnaire ≥ 8
Uncontrolled diabetes defined as HbA1c ≥ 9% at screening
Patients who are not candidates for liver biopsy
Presence of cirrhosis on liver biopsy or medical history |
-Exposición previa a elafibranor, CVC, tropifexor, ácido obeticólico (AO), LMB763 o cualquier otro agonista del FXR. -Participación en un ensayo clínico y tratamiento con cualquier producto en investigación para fibrosis hepática o EHNA en los 6 meses anteriores a la selección. -Pacientes que estén recibiendo medicación prohibida por el protocolo. En la Tabla 5-2 se muestra una descripción general de la medicación prohibida y en la Tabla 5-4, un resumen de la medicación permitida solo si se administra en una dosis estable. -Consumo significativo de alcohol o antecedentes durante un periodo superior a 3 meses consecutivos durante un año previo a la selección (se entiende por consumo significativo de alcohol más de 20 g/día en mujeres y más de 30 g/día en hombres, de media) y/o una puntuación en el cuestionario AUDIT modificado >/= 8. -Diabetes no controlada definida como HbA1c >/= 9 % en la selección. -Pacientes que no sean candidatos para una biopsia hepática. -Presencia de cirrosis en biopsia hepática o historia clínica |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Occurrence of adverse events, serious adverse events, adverse events resulting in discontinuation of study treatment, adverse events of special interest and changes in vital signs and laboratory values over 48 weeks of treatment |
La frecuencia de eventos adversos, de eventos adversos serios, de eventos adversos resultantes de la discontinuacion del tratamiento de estudio, eventos adversos de especial interés y cambios en los signos vitalesy labores de laboratorio durante 48 semanas. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Proportion of patients who have at least a one point improvement in fibrosis
Proportion of patients with resolution of steatohepatitis |
Proporción de pacientes que alcancen al menos un punto de mejoría en la fibrosis Proporción de pacientes que alcancen la resolución de la esteatohepatitis |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | 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 | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Argentina |
Belgium |
Canada |
Czech Republic |
Egypt |
Estonia |
France |
Germany |
Hong Kong |
India |
Israel |
Italy |
Latvia |
Portugal |
Russian Federation |
Singapore |
Spain |
Switzerland |
Turkey |
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
|
Last Visit Last Patient Last Site (LPLVLS) |
Última Visita del Último Paciente del Último Centro |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |