E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autoimmune Hepatitis (AIH) |
Epatite Autoimmune (AIH) |
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E.1.1.1 | Medical condition in easily understood language |
AIH is a chronic disease in which your body's immune system attacks the liver and causes inflammation and liver damage |
L'AIH è una malattia cronica in cui il sistema immunitario del tuo corpo attacca il fegato e provoca infiammazione e danni al fegato |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
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 | 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 |
AIH is a chronic disease in which your body's immune system attacks the liver and causes inflammation and liver damage |
• Valutare l'effetto di RO7049665 sul tempo alla recidiva dopo riduzione forzata dei CCS, misurata come il rapporto di rischio tra 7,5 mg di RO7049665 e placebo. |
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E.2.2 | Secondary objectives of the trial |
•To assess changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and IgG over time and by dose •To evaluate the effect of RO7049665 on time to relapse following forced CCS tapering as measured by the hazard ratio between 3.5 mg RO7049665 and placebo •To evaluate the safety and tolerability of RO7049665 in participants with AIH |
• Valutare i cambiamenti nei livelli di alanina aminotransferasi (ALT), aspartato aminotransferasi (AST) e immunoglobulina G (IgG) nel tempo e in base alla dose • Valutare l'effetto di RO7049665 sul tempo alla recidiva dopo riduzione forzata dei CCS, misurata come il rapporto di rischio tra 3,5 mg di RO7049665 e placebo. • Valutare la sicurezza e la tollerabilità di RO7049665 in partecipanti con AIH. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age •Age between 18 to 75 years Type of Participants and Disease Characteristics •Patients with a definite diagnosis of AIH (type 1, 2 and 3) as per simplified or revised original diagnostic criteria •Patients who have been in biochemical remission for > 2 years prior to randomization •Patients who have been on stable treatment for at least 6 months prior to randomization •No signs of liver inflammation on a liver biopsy taken no more than 12 months prior to randomization. •Patients with AIH who have previously not attempted to taper CCS to 0 mg/day Weight •Body mass index within the range of 18-35 kg/m2 (inclusive) Sex and Contraception/Barrier Requirements •Women of childbearing potential, who: agree to remain abstinent or use at least one acceptable contraceptive methods during the treatment period and for at least 28 days after the final dose of study drug |
Età • Età compresa tra 18 e 75 anni
Tipo di partecipanti e caratteristiche della malattia • Pazienti con una diagnosi definita di AIH (tipo 1, 2 e 3) secondo i criteri diagnostici originali semplificati • Pazienti in remissione biochimica da ¿ 2 anni prima della randomizzazione. • Pazienti in trattamento stabile da almeno 6 mesi prima della randomizzazione. • Nessun segno di infiammazione epatica alla biopsia epatica eseguita nei 12 mesi che precedono la randomizzazione. • Pazienti con AIH che in precedenza non hanno tentato una riduzione dei CCS a 0 mg/die. Peso • Indice di massa corporea compreso nell'intervallo 18 35 kg/m2 (compresi). Requisiti relativi ad attività sessuale e contraccezione/barriera • Donne in età fertile che: accetta di astenersi dai rapporti eterosessuali o di usare almeno un metodo contraccettivo accettabile durante il periodo di trattamento e per almeno 28 giorni dopo la dose finale del farmaco in studio. |
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E.4 | Principal exclusion criteria |
Medical Conditions •Patients with cirrhosis (F4 fibrosis by Fibroscan®) with significant impairment of liver function (Child Pugh category B or C) •Any other autoimmune disease requiring immunomodulating treatment •History of infection with hepatitis B, human immunodeficiency virus, active hepatitis C virus (HCV) infection, detection of replicating CMV or Epstein-Barr virus (EBV) •Active infections requiring systemic therapy with antibiotic, antiviral, or antifungal treatment or febrile illness within 7 days before Day-1 •History of primary or acquired immunodeficiency •Female patients: Pregnant or lactating •Symptomatic herpes zoster within 3 months prior to screening •History of active or latent tuberculosis or a positive Quantiferon Gold test •History of clinically significant severe drug allergies, multiple drug allergies, allergy to any constituent of the product, or intolerance to topical steroids •Lymphoma, leukemia, or any malignancy within the past 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years and in situ carcinoma of the cervix that was completely removed surgically. Breast cancer within the past 10 years •Significant uncontrolled comorbidity, such as cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders •Any condition or disease detected during the medical interview/physical examination that would render the patient unsuitable for the study, place the patient at undue risk, or interfere with the ability of the patient to complete the study in the opinion of the Investigator Prior/Concomitant Therapy •CCSs of < 5 mg/day, or < 2.5 mg CCSs plus immune suppressant, or < 3 mg/day budesonide with or without immune suppressant •CCSs > 20 mg/day or > 9 mg/day budesonide •NSI daily dose higher than recommended standard of care therapy •T or B cell-depleting therapy within the last 12 months or T- or B-cell number below normal due to depleting therapy Prior/Concurrent Clinical Study Experience •Leukocyte apheresis within 12 weeks of screening. •Donation of blood or blood products in excess of 500 mL within 3 months prior to screening. •Exposure to any investigational treatment within 6 months prior to Day 1 Laboratory Abnormalities •Abnormal hematologic, hepatic enzyme or hepatic function, biochemistry values Other Exclusions •History of regular alcohol consumption within 2 months of screening •Any suspicion or history of illicit drug use •Patients under judicial supervision, guardianship, or curatorship |
• Pazienti con cirrosi (fibrosi F4 con Fibroscan®) con compromissione significativa della funzionalità epatica (categoria B o C della classificazione Child Pugh). • Qualsiasi altra malattia autoimmune (inclusa sindrome da overlap) che richieda un trattamento immunomodulante. • Storia di infezione da virus dell'epatite B e/o per anti HBc infezione da virus dell'immunodeficienza umana (HIV; test per gli anticorpi anti-HIV positivo), infezione attiva da virus dell'epatite C (HCV) (RNA di HCV rilevabile), identificazione di CMV o virus di Epstein-Barr replicante. • Infezioni attive che richiedano terapia sistemica con antibiotici, antivirali o antifungini o malattia febbrile nei 7 giorni che precedono il giorno ¿1. • Anamnesi di immunodeficienza primaria o acquisita. • Pazienti femmine: gravidanza o allattamento con latte materno. • Herpes zoster sintomatico nei 3 mesi precedenti lo screening. • Anamnesi di tubercolosi attiva o latente o un test Quantiferon¿ Gold positivo. • Anamnesi di gravi allergie ai farmaci clinicamente significative, allergie a più farmaci, allergia a uno qualsiasi dei componenti del farmaco in studio o intolleranza agli steroidi per uso topico. • Linfoma, leucemia o qualsiasi tumore maligno nei precedenti 5 anni, tranne carcinoma a cellule basali o squamose della pelle che è stato resecato e non presenta evidenza di metastasi da 3 anni e carcinoma della cervice in situ che è stato rimosso completamente mediante chirurgia. Carcinoma mammario nei 10 anni precedenti. • Comorbilità significativa non controllata, quali patologie cardiache, polmonari, renali, epatiche, endocrine o gastrointestinali. • Qualsiasi condizione o patologia rilevata durante l'intervista medica/l'esame obiettivo che potrebbe rendere il paziente non idoneo allo studio, porre il paziente a un rischio superfluo o interferire con la capacità del paziente di completare lo studio secondo il parere dello sperimentatore. Terapie precedenti/concomitanti • CCS minore 5 mg/die o CCS < 2,5 mg più immunosoppressore o budesonide < 3 mg/die con o senza immunosoppressore. • CCS maggiore20 mg/die o budesonide > 9 mg/die. • Dose giornaliera di NSI maggiore dello standard di cura raccomandato. • Terapia di deplezione dei linfociti T o B (per es., rituximab) negli ultimi 12 mesi o conta dei linfociti T o B inferiore al normale a causa della terapia di deplezione Precedente/concomitante esperienza in uno studio clinico • Aferesi di linfociti nelle 12 settimane precedenti lo screening. • Donazione di sangue o emoderivati superiore a 500 ml nei 3 mesi che precedono lo screening. • Esposizione a qualsiasi prodotto sperimentale nei 6 mesi che precedono il giorno 1. • Valori ematologici anormali, Valori anormali degli enzimi epatici o della funzionalità epatica, Valori di biochimica anormali: Altre esclusioni • Storia di consumo regolare di alcool nei 2 mesi che precedono lo screening, • Sospetto o storia di consumo di droghe. • Pazienti sottoposti a sorveglianza giudiziaria, custodia o tutela. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to relapse from randomization |
Tempo alla recidiva dall'inizio della randomizzazione |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be assessed when the required number of events has occurred (Approximately 60 months) |
L'endpoint primario sarà valutato quando il numero richiesto di eventi si sono verificatii (Circa 60 mesi) |
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E.5.2 | Secondary end point(s) |
Efficacy 1.ALT, AST, and IgG (for both ¿, absolute and relative [upper limit of normal]) over time 2.Time to relapse from randomization 3.Incidence and severity of adverse events 4.Changes in vital signs, physical examination, ECG parameters, and safety laboratory parameters 5.Anti-drug antibody emergence and neutralizing potential |
Efficacy 1.ALT, AST, and IgG (for both ¿, absolute and relative [upper limit of normal]) over time 2.Time to relapse from randomization 3.Incidence and severity of adverse events 4.Changes in vital signs, physical examination, ECG parameters, and safety laboratory parameters 5.Anti-drug antibody emergence and neutralizing potential |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5. The secondary endpoints will be assessed when the required number of events has occurred (Approximately 60 months) |
1-5. The secondary endpoints will be assessed when the required number of events has occurred (Approximately 60 months) |
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
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 | 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 | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Australia |
Canada |
Korea, Democratic People's Republic of |
Korea, Republic of |
New Zealand |
Germany |
Italy |
Netherlands |
Portugal |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 |