E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-alcoholic Steatohepatitis (NASH). |
Steatoepatite non alcolica (NASH). |
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E.1.1.1 | Medical condition in easily understood language |
Fatty liver disease not related to alcohol intake. |
Steatoepatite non alcolica. |
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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 | 22.0 |
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 |
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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 |
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. |
L’obiettivo primario di questo studio è valutare la sicurezza e la tollerabilità di tropifexor + CVC nei pazienti con la NASH e fibrosi epatica di grado F2/F3 mediante monitoraggio degli eventi avversi, segni vitali e parametri di laboratorio durante le 48 settimane di terapia rispetto alla monoterapia con ognuna delle due molecole, tropifexor e CVC. |
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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. |
Caratterizzare l’efficacia di differenti dosi nella terapia di combinazione tropifexor + CVC nei pazienti con la NASH e fibrosi epatica di grado F2/F3 valutandone il beneficio tramite valutazione istologica dopo 48 settimane di terapia rispetto alle monoterapie (tropifexor e CVC) confrontando la biopsia finale con la biopsia al baseline. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained before any assessment is performed. 2. 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. 3. Adequate liver biopsy sample for evaluation by a central reader. 4. Presence of NASH as demonstrated by histologic evidence based on liver biopsy - NASH with fibrosis stage F2/F3, demonstrated on liver biopsy during the screening period. Alternatively, a historical biopsy can be used if performed within 6 months prior to screening, 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). |
1. Il consenso informato scritto deve essere ottenuto prima di qualsiasi valutazione 2. Pazienti maschi e femmine di almeno 18 anni (al momento della visita di screening). Per partecipare allo studio i pazienti devono avere un peso di almeno 50 Kg e non superiore a 200 Kg 3.Campione bioptico adeguato per la valutazione da parte del Patologo Centrale 4. Presenza di NASH comprovata istologicamente e fibrosi di grado F2/F3, dimostrata su una biopsia epatica eseguita durante il periodo di screening e valutata dal patologo centrale. In alternativa può essere utilizzata una biopsia epatica storica eseguita nei 6 mesi precedenti lo screening e valutata dal patologo centrale, se: - Il paziente è in terapia con uno qualsiasi dei farmaci elencati nella tabella 5-4 la cui dose è stabile da almeno 1 mese prima della biopsia e fino a e compresa la visita di screening - Il peso del paziente si è mantenuto stabile (perdita di peso pari al massimo al 10% dalla biopsia fino a e compresa la visita di screening). |
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E.4 | Principal exclusion criteria |
1. Previous exposure to elafibranor, CVC, tropifexor, obeticholic acid (OCA), LMB763 or any other FXR agonist. 2. 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 (subjects documented to be assigned to placebo in such trials may be eligible immediately following completion of their participation in the previous trial). 3. Patients taking medications prohibited by the protocol. An overview of prohibited medications is given in Table 5-2, and the summary of medications permitted only if on stable dose is in Table 5-4 4. Current or history of significant alcohol consumption for a period ofmore 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 5. Uncontrolled diabetes defined as glycated hemoglobin (HbA1c) = 9% at screening 6. Patients who are not candidates for liver biopsy 7. Presence of cirrhosis on liver biopsy or medical history |
1. Precedente esposizione a elafibranor, CVC, tropifexor, acido obeticolico, LMB763 o qualsiasi altro agonista del recettore FXR 2. Partecipazione a uno studio clinico e terapia con qualsiasi prodotto sperimentale valutato per il trattamento della fibrosi epatica o della NASH nei 6 mesi precedenti la visita di screening (i soggetti con documentata assegnazione al braccio placebo in questi trials possono essere eleggibili immediatamente dopo aver terminato la loro partecipazione al precedente trial) 3. Pazienti in terapia con farmaci proibiti per lo studio. La tabella 5-2 (nel protocollo) contiene l’elenco dei farmaci proibiti mentre la tabella 5-4 (nel protocollo) contiene un elenco dei farmaci consentiti solo se a dose stabile 4. Storia o uso significativo di alcol per un periodo superiore ai 3M consecutivi nell'anno precedente lo screening (uso significativo di alcol: consumo giornaliero superiore a 20g/day per le donne e superiore a 30g/day per gli uomini, in media) e/o un punteggio del questionario AUDIT modificato =8 5. Diabete non controllato definito come emoglobina glicata (HbA1c) =9% allo screening 6. Pazienti che non possono eseguire la biopsia epatica 7. Presenza di cirrosi sul referto della biopsia epatica o nella storia medica del paziente |
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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. |
Presenza di eventi avversi, eventi avversi gravi, eventi avversi che hanno comportato l'interruzione del trattamento in studio, eventi avversi di particolare interesse e cambiamenti dei segni vitali e dei valori di laboratorio. |
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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) |
1. Proportion of patients who have at least a one point improvement in fibrosis. 2. Proportion of patients with resolution of steatohepatitis. |
1. Proporzione di pazienti che presentano un miglioramento di almeno un punto nella fibrosi. 2. Proporzione di pazienti con risoluzione di steatoepatite. |
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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 | 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 | Information not present in EudraCT |
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 |
Brazil |
Canada |
Chile |
Czechia |
Egypt |
Estonia |
France |
Germany |
Hong Kong |
India |
Israel |
Italy |
Latvia |
Mexico |
Portugal |
Russian Federation |
Singapore |
Spain |
Switzerland |
Turkey |
United Kingdom |
United States |
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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
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Last Visit Last Patient Last Site (LPLVLS) |
Last Visit Last Patient Last Site (LPLVLS) |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |