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Seguridad y eficacia a largo plazo de odevixibat en pacientes con síndrome de Alagille (ASSERT-EXT)

20 de octubre de 2026 actualizado por: Albireo, an Ipsen Company

Un estudio abierto para evaluar la seguridad y eficacia a largo plazo de odevixibat (A4250) en pacientes con síndrome de Alagille (ASSERT-EXT)

The purpose of this study is to assess the long-term safety and effectiveness of odevixibat in participants with Alagille syndrome (ALGS).

The participants of this study will have ALGS a rare genetic disorder that can affect multiple organ systems of the body including the liver, heart, skeleton, eyes and kidneys. Common symptoms, which often develop during the first three months of life, include blockage of the flow of bile from the liver (cholestasis), yellowing of the skin and mucous membranes (jaundice), poor weight gain and growth and severe itching (pruritis).

The drug used for the study is odevixibat and was authorized for the treatment of cholestatic pruritus in infants with ALGS over 12 months of age by the United States Food and Drug Administration on 13 June 2023.

Descripción general del estudio

Estado

Activo, no reclutando

Condiciones

Intervención / Tratamiento

Descripción detallada

This Phase 3, open-label, multi-center extension study will have two groups of participants: Cohort 1 (participants who participated in Study A4250-012 [NCT04674761; ASSERT] and meet the entry criteria for this study) and Cohort 2 (infants under 12 months of age) with ALGS.

The study will consist of 2 or 3 periods:

  1. A 'Treatment period' of 72 weeks (cohort 1) or 12 weeks (cohort 2). Participants will visit the clinic every 4 to 12 weeks and will receive a dose of 120 μg/kg odevixibat daily.
  2. An 'Optional extension period' where participants who wish to continue receiving odevixibat after the 'treatment period' will have the opportunity to remain on treatment with visits every 16 weeks until the drug is commercially available. The optional extension is available provided continued use is supported by the risk-benefit profile, the participant has not been previously withdrawn or discontinued from the study, and the study is not terminated by the Sponsor.
  3. A 'Safety follow-up period' of 4 weeks (cohort 1) or 2 weeks (cohort 2). The Safety Follow-up Period will not occur for those who remain on treatment in the optional extension period.

Participants will need to complete an e-diary and questionnaires throughout the study (cohort 1 only). Participants will undergo blood samplings, urine collections (cohort 1 only), physical examinations, and clinical evaluations. They may continue some other medications, but the details need to be recorded.

Tipo de estudio

Intervencionista

Inscripción (Actual)

62

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Alemania
      • Berlin, Alemania, 13353
        • Charité - Universitätsmedizin Berlin
      • Hanover, Alemania, 30625
        • Medizinische Hochschul
      • Tübingen, Alemania, 72076
        • Universitatsklinik fur Kinder-und Jugendmedizin Tubingen
  • Bélgica
      • Brussels, Bélgica, 1200
        • Cliniques Universitaires Saint-Luc Bruxelles
  • Estados Unidos
    • California
      • San Diego, California, Estados Unidos, 92123
        • Rady Children's Hospital
      • San Francisco, California, Estados Unidos, 94158
        • UCSF
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30329
        • Children's Healthcare of Atlanta
    • Indiana
      • Indianapolis, Indiana, Estados Unidos, 46202
        • Riley Hospital for Children at IU Health
    • Maryland
      • Baltimore, Maryland, Estados Unidos, 21287
        • Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02115
        • Boston Children's Hospital
    • Missouri
      • Kansas City, Missouri, Estados Unidos, 64018
        • Children's Mercy Hospital and Clinics
    • New York
      • New Hyde Park, New York, Estados Unidos, 11042
        • Northwell Health System
      • New York, New York, Estados Unidos, 10016
        • Hassenfeld Children's Hospital at NYU Langone
      • New York, New York, Estados Unidos, 10032
        • New York-Presbyterian / Columbia University Irving Medical Center
      • The Bronx, New York, Estados Unidos, 10467
        • The Childrens Hospital at Montefiore Albert Einstein School of Medicine
    • North Carolina
      • Durham, North Carolina, Estados Unidos, 27710
        • Atrium Health Carolinas Medical
    • Ohio
      • Cincinnati, Ohio, Estados Unidos, 45229
        • Cincinnati Children's Hospital
    • Oregon
      • Portland, Oregon, Estados Unidos, 97239
        • Oregon Health Science University School of Medicine
    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37232
        • Monroe Carell Jr. Childrens Hospital at Vanderbilt
    • Texas
      • Dallas, Texas, Estados Unidos, 75207
        • Childrens Medical Center of Dallas University of Texas Southwestern
      • Houston, Texas, Estados Unidos, 77030
        • Texas Children's Hospital
      • San Antonio, Texas, Estados Unidos, 78215
        • Texas Liver Institute
  • Francia
      • Bron, Francia, 69677
        • Hôpital Femme Mère Enfant de Lyon
      • Lille, Francia
        • Antenne pediatrique du CIC-Hopital Jeanne De Flandre
      • Paris, Francia, 75015
        • Hopital Necker Enfants Malades
  • Italia
      • Florence, Italia
        • AOU Meyer
      • Padova, Italia, 35128
        • Azienda Ospedale University
      • Rome, Italia, 00165
        • Ospedale Pediatrico Bambino Gesu
  • Malasia
      • Kuala Lumpur, Malasia, 59100
        • University of Malaya Medical Center
  • Países Bajos
      • Groningen, Países Bajos, 9713 GZ
        • Universitair Medisch Centrum Groningen
      • Utrecht, Países Bajos
        • Wilhelmina Children's Hospital UMCU Utrecht
  • Polonia
      • Warsaw, Polonia, 04-730
        • Instytut Pomnik-Centrum Zdrowia Dzieck
  • Reino Unido
      • Birmingham, Reino Unido
        • Birmingham Women's and Children's NHS Foundation Trust
      • London, Reino Unido, SE5 9RS
        • King's College Hospital NHS Foundation Trust King's College Hospital Paediatric Research
  • Turquía (Türkiye)
      • Istanbul, Turquía (Türkiye)
        • Istanbul University Istanbul Medical Faculty Hospital

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Niño
  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

Cohort 1 :

  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.

Cohort 2 :

  1. Infant with clinically confirmed ALGS , ≤11 months of age at Study Day 1
  2. Body weight ≥2 kg at Study Day 1
  3. Gestational age ≥36 weeks. For children born with gestational age between 32 and 36 weeks, a postmenstrual age of ≥36 weeks is required .
  4. Signed parent/legal guardian informed consent.

Exclusion Criteria:

Cohort 1 :

  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

Cohort 2 :

  1. Patient with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following:

    1. Biliary atresia of any kind
    2. Progressive familial intrahepatic cholestasis (PFIC)
    3. Benign recurrent intrahepatic cholestasis

  2. Patient with a past medical history or ongoing presence of any other disease or condition known to interfere with the absorption, distribution, metabolism (specifically bile acid metabolism), or excretion of drugs in the intestine, including but not limited to, inflammatory bowel disease

  3. Patient with past medical history or ongoing chronic diarrhea requiring intravenous fluid or nutritional intervention for treatment of the diarrhea and/or its sequelae

  4. Patient has a confirmed past diagnosis of infection with human immunodeficiency virus or other present and active, clinically significant chronic infection

  5. Recent infection requiring hospitalization or treatment with parenteral anti-infective within 4 weeks of Study Day 1 or completion of oral anti-infective treatment within 2 weeks prior to the Screening Visit

  6. Cancer diagnosis (except for basal cell carcinoma)

  7. Chronic kidney disease with an impaired renal function and a glomerular filtration rate <70 mL/min/1.73 m2

  8. Patient with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to the Screening Visit

  9. Patient has had a liver transplant, or a liver transplant is planned within 6 months of Study Day 1

  10. Decompensated liver disease, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy

  11. International normalized ratio (INR) >1.4 (the patient may be treated with Vitamin K, and if INR is ≤1.4 at resampling the patient may be enrolled)

  12. Serum alanine aminotransferase (ALT) >10 × upper limit of normal (ULN) at Screening

  13. Serum ALT >15 × ULN at any time point during the last 6 months unless an alternate etiology was confirmed for the elevation

  14. Total bilirubin >15 × ULN at Screening

  15. Patient suffers from uncontrolled, recalcitrant pruritic condition other than ALGS. Examples include, but not limited to, refractory atopic dermatitis or other primary pruritic skin diseases.

  16. Patient exposed to alcohol or substance abuse in utero

  17. Bile acid or lipid binding resins and medications that slow gastrointestinal motility

  18. Patient has had investigational exposure to a drug, biologic agent, or medical device within 30 days prior to the Screening Visit, or 5 half-lives of the study agent, whichever is longer

  19. 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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Odevixibat (A4250)

Capsules for oral administration once daily for 72 weeks.
Droga: Odevixibat

Odevixibat is a small molecule and selective inhibitor of IBAT.

Otros nombres:
  • A4250

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Cambio desde el inicio en medicamentos concomitantes.
Periodo de tiempo: Línea de base hasta la semana 12 (cohorte 2).
Línea de base hasta la semana 12 (cohorte 2).
Cambio con respecto al valor inicial en los niveles de vitaminas liposolubles.
Periodo de tiempo: Línea de base hasta la semana 12 (cohorte 2).
Línea de base hasta la semana 12 (cohorte 2).
Change from baseline in pruritus
Periodo de tiempo: Baseline to week 72 (cohort 1).

Assessed as change in scratching score as measured by measured by the Albireo Observer-Reported Outcome Caregiver Instrument.
Baseline to week 72 (cohort 1).
Percentage of participants with Treatment Emergent Adverse Event (TEAEs) and Serious Adverse Events (SAEs)
Periodo de tiempo: Baseline to week 12 (cohort 2).

An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is an AE that results in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events. TEAEs included both Serious TEAEs and non-serious TEAEs.
Baseline to week 12 (cohort 2).
Percentage of participants with clinically significant changes from baseline in Physical Examination
Periodo de tiempo: Baseline to week 12 (cohort 2).

The clinical significance will be graded by the investigator.
Baseline to week 12 (cohort 2).
Percentage of participants with clinically significant changes in Laboratory Parameters
Periodo de tiempo: Baseline to week 12 (cohort 2).

The following laboratory parameters will be reported: blood chemistry, hematology and coagulation. The clinical significance will be graded by the investigator.
Baseline to week 12 (cohort 2).
Percentage of participants with clinically significant changes from baseline in Vital Signs.
Periodo de tiempo: Baseline to week 12 (cohort 2).

The clinical significance will be graded by the investigator.
Baseline to week 12 (cohort 2).

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Cambio desde el valor inicial en los niveles de ácidos biliares séricos
Periodo de tiempo: Línea de base hasta la semana 72 (cohorte 1).
Línea de base hasta la semana 72 (cohorte 1).
Cambio desde el valor inicial en los niveles de ácidos biliares séricos.
Periodo de tiempo: Línea de base hasta la semana 72 (cohorte 1).
Línea de base hasta la semana 72 (cohorte 1).
Número de participantes con cambios desde el inicio en el examen físico
Periodo de tiempo: Línea de base hasta la semana 72 (cohorte 1).
Línea de base hasta la semana 72 (cohorte 1).
Número de participantes con cambios desde el inicio en los signos vitales
Periodo de tiempo: Línea de base hasta la semana 72 (cohorte 1).
Línea de base hasta la semana 72 (cohorte 1).
Cambio desde el inicio en medicamentos concomitantes
Periodo de tiempo: Línea de base hasta la semana 72 (cohorte 1).
Línea de base hasta la semana 72 (cohorte 1).
Cambio desde el valor inicial en los resultados de las pruebas de laboratorio Cmax farmacocinética (PK) [Marco de tiempo: día 1, semana 4, semana 8 y semana 12]
Periodo de tiempo: Línea de base hasta la semana 72 (cohorte 1).
Línea de base hasta la semana 72 (cohorte 1).
Cambio desde el valor inicial en la concentración plasmática del fármaco del estudio
Periodo de tiempo: Día 1, Semana 4, Semana 8 y Semana 12 (cohorte 1).
Día 1, Semana 4, Semana 8 y Semana 12 (cohorte 1).
Parámetros farmacodinámicos: cambio en los niveles séricos de ácidos biliares.
Periodo de tiempo: Línea de base hasta la semana 12 (cohorte 2).
Línea de base hasta la semana 12 (cohorte 2).
Change from baseline in patient reported and observer reported itching and scratching severity scores
Periodo de tiempo: Baseline to week 72 (cohort 1).

Assessed by the the Albireo ObsRO/ Patient Reported Outcomes (PRO) instruments. The Albireo ObsRO/PRO scratching and itch severity items use 0 to 4 response scales, where each response is distinguished by a unique facial expression, verbal anchor, number, and color code.
Baseline to week 72 (cohort 1).
Percentage of participants achieving a clinically meaningful decrease in pruritus (pruritus responders)
Periodo de tiempo: Baseline to week 72 (cohort 1).

Assessed by the Albireo ObsRO/patient reported outcomes (PRO) instruments
Baseline to week 72 (cohort 1).
Change from baseline in sleep parameters.
Periodo de tiempo: Baseline to week 72 (cohort 1).

Assessed with the Albireo ObsRO/PRO instruments (e.g: tiredness and number of awakenings).
Baseline to week 72 (cohort 1).
Change from baseline in Pediatric Quality of Life Inventory (PedsQL) scores.
Periodo de tiempo: Baseline to week 72 (cohort 1).

The PedsQL instrument consists of 36 questions and uses a 5-point response scales, where higher scores indicates worst symptoms.
Baseline to week 72 (cohort 1).
Change from baseline in in Global Symptom Relief: Patient Global Impression of Improvement (PGIC) score.
Periodo de tiempo: Baseline to Weeks 4, 12, 24, 48 and 72 (cohort 1).

The Patient Global Impression of Change (PGIC) is a patient-reported instrument that measures change in overall status on a scale ranging from one ("very much improved") to seven ("very much worse").
Baseline to Weeks 4, 12, 24, 48 and 72 (cohort 1).
Change from baseline in in Global Symptom Relief: Clinical Global Impression of Improvement (CGIC) score.
Periodo de tiempo: Baseline to Weeks 4, 12, 24, 48 and 72 (cohort 1).

The Clinical Global Impression of Change (CGIC) is a clinician-reported instrument that measures change in overall status on a scale ranging from one ("very much improved") to seven ("very much worse").
Baseline to Weeks 4, 12, 24, 48 and 72 (cohort 1).
Change from baseline in in Global Symptom Relief: Caregiver Global Impression of Change (CaGIC) score
Periodo de tiempo: Baseline to Weeks 4, 12, 24, 48 and 72 (cohort 1).

The caregiver Global Impression of Change is a caregiver-reported instrument that measures change in overall status on a scale ranging from one ("very much improved") to seven ("very much worse").
Baseline to Weeks 4, 12, 24, 48 and 72 (cohort 1).
Percentage of participants with Treatment Emergent Adverse Event (TEAEs) and Serious Adverse Events (SAEs)
Periodo de tiempo: Baseline to week 72 (cohort 1).

An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is an AE that resultes in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events. TEAEs included both Serious TEAEs and non-serious TEAEs.
Baseline to week 72 (cohort 1).

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Albireo, an Ipsen Company

Investigadores

  • Director de estudio: Ipsen Medical Director, Ipsen

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

3 de septiembre de 2021

Finalización primaria (Estimado)

15 de febrero de 2027

Finalización del estudio (Estimado)

15 de febrero de 2027

Fechas de registro del estudio

Enviado por primera vez

13 de agosto de 2021

Primero enviado que cumplió con los criterios de control de calidad

1 de septiembre de 2021

Publicado por primera vez (Actual)

5 de septiembre de 2021

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

23 de octubre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

20 de octubre de 2026

Última verificación

1 de octubre de 2026

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • A4250-015
  • 2023-509028-17-00 (Ctis)
  • 2021-000996-36 (Número EudraCT)
  • 2023 (Subvención/contrato del NIH de EE. UU.)

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Descripción del plan IPD

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications.

Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

Marco de tiempo para compartir IPD

Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU.

Criterios de acceso compartido de IPD

Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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