| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Alagille Syndrome |
| Sindrome di Alagille |
|
| E.1.1.1 | Medical condition in easily understood language |
| Alagille syndrome is a childhood disease that affects the liver and different parts of the body. These children have buildup of a fluid made by the liver called bile which can cause severe itch. |
| La sindrome di Alagille è una malattia infantile che colpisce il fegato e varie parti del corpo.Questi bambini hanno un accumulo di un fluido prodotto dal fegato(bile)che può causare un forte prurito. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
| 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 | 10053870 |
| E.1.2 | Term | Alagille syndrome |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
| 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 demonstrate a sustained effect of odevixibat on pruritus in patients with ALGS who have completed study A4250-012 (ASSERT). |
| Dimostrare un effetto prolungato di odevixibat sul prurito in pazienti affetti da ALGS che hanno completato lo studio A4250-012 (ASSERT). |
|
| E.2.2 | Secondary objectives of the trial |
- To demonstrate a sustained effect of odevixibat on serum bile acids in patients with ALGS who have completed study A4250-012;
- To evaluate an effect of odevixibat on parameters related to quality of life;
- To evaluate the long-term safety and tolerability of repeated daily doses of odevixibat in patients with ALGS. |
- Dimostrare un effetto prolungato di odevixibat sui livelli sierici di acidi biliari in pazienti affetti da ALGS che hanno completato lo studio A4250-012;
- Valutare l’effetto di odevixibat sui parametri relativi alla qualità della vita;
- Valutare la sicurezza e la tollerabilità a lungo termine di dosi giornaliere ripetute di odevixibat in pazienti affetti da ALGS. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Completion of the 24-week Treatment Period of Study A4250-012;
2. Signed informed consent and assent as appropriate. Patients who turn 18 years of age (or legal age per country) during the study will be required to re-consent to remain on the study;
3. Caregivers (and age-appropriate patients) must be willing and able to use an electronic diary (eDiary) device as required by the study;
4. Sexually active males and females must agree to use a reliable contraceptive method with = 1% failure rate (such as hormonal contraception, intra-uterine device, or complete abstinence) from signed informed consent through 90 days after last dose of study drug. |
1.Completamento del periodo di trattamento di 24 settimane dello studio A4250-012;
2.Firma del consenso informato e dell'assenso, ove appropriato. I pazienti che compiono 18 anni (o l'età legale secondo il Paese) durante lo studio dovranno rinnovare il consenso per rimanere nello studio;
3.I caregiver (e i pazienti di età appropriata) devono essere disposti a, e in grado di utilizzare un diario elettronico (eDiary) come richiesto dallo studio;
4.I soggetti di sesso maschile e femminile sessualmente attivi devono accettare di utilizzare un metodo contraccettivo affidabile con un tasso di insuccesso = 1% (come contraccezione ormonale, dispositivo intrauterino o astinenza completa) a partire dalla firma del consenso informato e per 90 giorni dopo l’ultima dose del farmaco in studio. |
|
| E.4 | Principal exclusion criteria |
1. Decompensated liver disease, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy;
2. Patients who were not compliant with study drug treatment or procedures in Study A4250-012;
3. Any other conditions or abnormalities which, in the opinion of the investigator, may compromise the safety of the patient, or interfere with the patient participating in or completing the study;
4. Known hypersensitivity to any components of odevixibat. |
1.Malattia epatica scompensata, anamnesi o presenza di ascite clinicamente significativa, emorragia da varici e/o encefalopatia;
2.Pazienti che non hanno seguito il trattamento o le procedure con il farmaco in studio durante lo studio A4250-012;
3.Altra condizione o anomalia che, a giudizio dello sperimentatore, possa compromettere la sicurezza del/la paziente o interferire con la partecipazione o il completamento dello studio da parte del/la paziente;
4.Ipersensibilità nota a uno dei componenti di odevixibat. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in scratching through Week 72 as measured by the Albireo ObsRO caregiver instrument. |
| Variazione del grattarsi dal basale alla settimana 72 misurata mediante lo strumento Albireo ObsRO (esiti riferiti dall’osservatore). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Change from baseline in scratching through Week 72. |
| Variazione del grattarsi dal basale alla settimana 72. |
|
| E.5.2 | Secondary end point(s) |
• Change in serum bile acid levels from baseline to Week 72;
• Change from baseline through Week 72 in patient reported and observer reported itching and scratching severity scores, respectively, for the morning and evening assessment;
• Percentage of patients achieving a clinically meaningful decrease in pruritus (pruritus responders) as measured by the Albireo ObsRO/patient reported outcomes (PRO) instruments;
• Change from baseline to Week 72 in sleep parameters as measured with the Albireo ObsRO/PRO instruments (e.g. tiredness and number of awakenings);
• Change from baseline to Week 72 in Pediatric Quality of Life Inventory (PedsQL) scores;
• Assessment of Global Symptom Relief from baseline to Weeks 4, 12, 24, 48, and 72 as measured by patient, caregiver, and clinician Global impression of Symptoms (PGIS, CaGIS, CGIS) items;
• Assessment of Global Symptom Relief as measured by patient, caregiver, and clinician Global Impression of Change (PGIC, CaGIC, CGIC) items at Weeks 4, 12, 24, 48, and 72;
• Change in serum bile acid levels from baseline through Week 72. |
• Variazione dei livelli sierici di acidi biliari dal basale alla settimana 72;
• Varazione dal basale alla settimana 72 dei punteggi di gravità del prurito e del grattarsi riferiti dal/la paziente e dall’osservatore, rispettivamente, per la valutazione mattutina e serale;
• Percentuale di pazienti che raggiungono una riduzione clinicamente significativa del prurito (responder per prurito) misurata dagli strumenti Albireo ObsRO/PRO (esiti riferiti dal paziente);
• Variazione dal basale alla settimana 72 dei parametri del sonno misurati con gli strumenti Albireo ObsRO/PRO (ad es. stanchezza e numero di risvegli);
• Variazione dal basale alla settimana 72 dei punteggi del PedsQL (Pediatric Quality of Life Inventory);
• Valutazione del sollievo globale dei sintomi dal basale alle settimane 4, 12, 24, 48 e 72 secondo la misurazione effettuata dal paziente, dal caregiver e dal medico in base all’impressione globale dei sintomi (PGIS, CaGIS, CGIS);
• Valutazione del sollievo globale dei sintomi effettuata dal paziente, dal caregiver e dal medico in base all’impressione globale del cambiamento (PGIC, CaGIC, CGIC) alle settimane 4, 12, 24, 48 e 72;
• Variazione dei livelli sierici di acidi biliari dal basale alla settimana 72. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Change in serum bile acid levels from baseline through Week 72;
• Change from baseline through Week 72;
• Assessment of Global Symptom Relief from baseline to Weeks 4, 12, 24, 48, and 72. |
• Variazione dei livelli sierici di acidi biliari dal basale alla settimana 72;
• Varazione dal basale alla settimana 72;
• Valutazione del sollievo globale dei sintomi dal basale alle settimane 4, 12, 24, 48 e 72. |
|
| 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 | No |
| 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) | No |
| 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 | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | 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 |
| Belgium |
| Canada |
| France |
| Germany |
| Israel |
| Italy |
| Malaysia |
| Netherlands |
| New Zealand |
| Poland |
| 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
|
The end of the study is defined as follows:
• End of study for a patient: last study visit by the patient, either at the clinic or via telephone, whichever comes latest;
• End of study in one country: last patient last visit (LPLV) in the country and sites in the country are closed
• End of study globally: LPLV globally and all study sites closed. |
La fine dello studio è definita come segue:
• Fine dello studio per un paziente: ultima visita di studio del paziente, in ambulatorio o telefonicamente, a seconda di quale si verifica per ultima;
• Fine dello studio in un paese: l'ultima visita dell'ultimo paziente (LPLV) nel paese e i centri nel paese sono chiusi;
• Fine dello studio a livello globale: LPLV a livello globale e tutti i centri studio chiusi. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| 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 | 15 |
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