E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary biliary cholangitis |
Colangite biliare primaria |
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E.1.1.1 | Medical condition in easily understood language |
A type of long-term liver disease in which the bile ducts in the liver become damaged. |
Un tipo di malattia epatica a lungo termine in cui i dotti biliari nel fegato vengono danneggiati |
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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 | SOC |
E.1.2 | Classification code | 10019805 |
E.1.2 | Term | Hepatobiliary disorders |
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 |
To evaluate the efficacy of 3 doses of RhuDex vs placebo for the treatment of PBC in patients with an inadequate response to UDCA. |
Valutare l'efficacia di 3 dosi di RhuDex vs placebo per il trattamento della CBP in pazienti con una risposta inadeguata all'UDCA. |
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E.2.2 | Secondary objectives of the trial |
- To identify efficacious RhuDex dose(s) for the treatment of PBC for further evaluation in phase III - To study safety and tolerability of RhuDex |
- Identificare la dose(i) di RhuDex efficace per il trattamento della CBP per la valutazione successiva in Fase III - Studiare la sicurezza e la tollerabilità di RhuDex |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient is able to understand the information on the trial and has signed the informed consent form, - Male or female patients = 18 and < 74 years, - PBC verified by at least 2 out of the following 3 criteria (consistent with EASL practice guidelines [2017]): • Chronic cholestatic disease (e.g. elevated serum ALP) of at least 6 months duration, • Positive AMA titer or presence of PBC-specific antibodies, • Liver biopsy compatible with the diagnosis of non-cirrhotic PBC, - UDCA treatment for at least 6 months (with a stable dose for = 3 months of at least 12 mg/kg/day) prior to baseline, - Serum ALP levels between 1.5x and 10x the upper limit of normal (ULN) at screening, - Women of childbearing potential agree to use during the entire duration of the trial and until 4 weeks following the last dose of trial treatment a highly effective method of birth control. |
- Il paziente è in grado di comprendere le informazioni sullo studio e ha firmato il modulo di consenso informato, - Pazienti maschi o femmine di età = 18 e <74 anni, - CBP confermata da almeno 2 dei 3 seguenti criteri (coerenti con le linee guida EASL [2017]): • Colesteasi cronica (ad es. ALP sierica elevata) della durata di almeno 6 mesi, • Titolo anticorpale AMA positivo o presenza di anticorpi specifici per CBP, • Biopsia epatica compatibile con la diagnosi di CBP non cirrotica, - trattamento con UDCA per almeno 6 mesi (con una dose stabile = 3 mesi di almeno 12 mg / kg / giorno) prima del basale, - Livelli sierici di ALP compresi tra 1,5 e 10 volte il limite superiore della norma (ULN) allo screening, - Le donne in età fertile accettano di utilizzare durante l'intera durata della sperimentazione e fino a 4 settimane dopo l'ultima dose di trattamento un metodo di controllo delle nascite altamente efficace. |
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E.4 | Principal exclusion criteria |
- History or presence of other relevant concomitant liver diseases - Liver cirrhosis - History or presence of hepatic decompensation (e.g. variceal bleeding hepatic encephalopathy or poorly controlled ascites), - Serum albumin less than 3.2 g/dL, at screening, - Any known relevant infectious disease (e.g. active tuberculosis, acquired immunodeficiency syndrome [AIDS]-defining diseases), - Abnormal renal function (glomerular filtration rate estimated from cystatin C < 30 mL/min) at screening visit, - Thyroid-stimulating hormone (TSH) > ULN at screening (elevated levels [4.2-10 µU/mL] are acceptable if free thyroxine 4 (fT4) is measured and within the normal range), - Current history of significant alcohol consumption (> 30 g/day in men, > 20 g/day in women on average) for a period of more than 3 consecutive months within 1 year prior to screening, - Any illness or medical conditions that are unstable or could jeopardise the safety of the patient and his/her compliance in the trial or might interfere with the trial results, - Previous or concurrent cancer except cervical carcinoma in situ, treated basal cell carcinoma, or any cancer curatively treated < 3 years before trial entry, - Existing or intended pregnancy or breast-feeding. |
- Storia o presenza di altre malattie epatiche concomitanti rilevanti - Cirrosi epatica - Anamnesi o presenza di scompenso epatico (ad esempio, encefalopatia epatica da sanguinamento da varici o ascite scarsamente controllata), - Albumina sierica inferiore a 3,2 g/dL, allo screening, - Qualsiasi malattia infettiva rilevante nota (ad es. Tubercolosi attiva, sindrome da immunodeficienza acquisita [AIDS]), - Funzionalità renale anormale (velocità di filtrazione glomerulare stimata mediante cistatina C <30 mL / min) alla visita di screening, - Ormone tireostimolante (TSH)> ULN allo screening (livelli elevati [4,2-10 µU / mL] sono accettabili se viene misurata la tiroxina libera 4 (fT4) e rientra nell'intervallo normale), - Storia di consumo significativo di alcol (> 30 g/giorno negli uomini,> 20 g/giorno nelle donne in media) per un periodo di oltre 3 mesi consecutivi nell'anno precedente lo screening, - Qualsiasi malattia o condizione medica instabile o che possa mettere a rischio la sicurezza del paziente e la sua adesione allo studio o che possa interferire con i risultati dello studio, - Precedente o concomitante malattia tumorale ad eccezione del carcinoma cervicale in situ, carcinoma basocellulare trattato o qualsiasi tumore trattato con terapia curativa <3 anni prima dell'ingresso nello studio, - Gravidanza o allattamento in atto o previste. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: • Relative change (%) in Alkaline phosphatase (ALP) from baseline to End Of Trial (EoT).
Safety Endpoints: • Adverse Events, • Vital signs (blood pressure, heart rate), body temperature, body weight and BMI, • Haematology, serum chemistry, urinalysis, coagulation, • ECG parameters (12 leads), • Patient's tolerability of the IMP. |
End point primario di Efficacia: • Variazione relativa (%) della fosfatasi alcalina (ALP) dal basale fino alla fine del periodo di trattamento (EoT).
End point di Sicurezza: • Eventi avversi, • Segni vitali (pressione sanguigna, frequenza cardiaca), temperatura corporea, peso e BMI, • Ematologia, sierologico, analisi delle urine, coagulazione, • Parametri ECG (12 derivazioni), • Tollerabilità dell'IMP da parte del paziente. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the study |
Tutta la durata dello studio |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints: - ALP at each trial visit (screening to follow-up), - Absolute and relative changes (%) of ALP from baseline to each visit up to EOT, and from EOT to the follow-up visit, - gamma-GT, AST, ALT, and total and conjugated bilirubin levels at each trial visit (screening to follow-up), - Absolute and relative changes (%) of gamma-GT, AST, ALT and total and conjugated bilirubin levels from baseline to each visit up to EOT, and from EOT to the follow-up visit.; End point secondari di Efficacia: - ALP ad ogni visita (dallo screening al follow-up) - Variazione assoluta e relativa (%) di ALP dal baseline a ciascuna visita fino all' EOT, e dall' EOT alla visita di follow-up - livelli di gamma-GT, AST, ALT e bilirubina totale e coniugata ad ogni visita di studio (dallo screening al follow-up), - Variazioni assolute e relative (%) di gamma-GT, AST, ALT e livelli di bilirubina totale e coniugata dal basale a ciascuna visita fino all' EOT e dall' EOT alla visita di follow-up. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the study; Tutta la durata dello studio |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | Information not present in EudraCT |
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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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |