Long-term Safety and Efficacy of Odevixibat in Patients With Alagille Syndrome

NCT05035030 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: A4250-0152023-509028-17-002021-000996-36
• Study Type: interventional
• Target: 70
• Locations: 13 countries
• Sites: 39

Brief Summary

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.

Conditions

Alagille Syndrome

Outcome Measures

Primary Outcomes (7)

• Change from baseline in pruritus

  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)

  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

  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

  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.

  The clinical significance will be graded by the investigator.

  Baseline to week 12 (cohort 2).

• Change from baseline in concomitant medications.

  Baseline to week 12 (cohort 2).

• Change from baseline in fat-soluble vitamin levels.

  Baseline to week 12 (cohort 2).

Secondary Outcomes (16)

• Change from baseline in serum bile acids levels

  Baseline to week 72 (cohort 1).

• Change from baseline in patient reported and observer reported itching and scratching severity scores

  Baseline to week 72 (cohort 1).

• Percentage of participants achieving a clinically meaningful decrease in pruritus (pruritus responders)

  Baseline to week 72 (cohort 1).

• Change from baseline in sleep parameters.

  Baseline to week 72 (cohort 1).

• Change from baseline in Pediatric Quality of Life Inventory (PedsQL) scores.

  Baseline to week 72 (cohort 1).

Study Arms (1)

Odevixibat (A4250)

EXPERIMENTAL

Capsules for oral administration once daily for 72 weeks.

Drug: Odevixibat

Interventions

Odevixibat DRUG

Odevixibat is a small molecule and selective inhibitor of IBAT.

Also known as: A4250

Odevixibat (A4250)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1 :
• Completion of the 24-week Treatment Period of Study A4250-012
• 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
• Caregivers (and age-appropriate patients) must be willing and able to use an electronic diary (eDiary) device as required by the study
• 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 :
• Infant with clinically confirmed ALGS , ≤11 months of age at Study Day 1
• Body weight ≥2 kg at Study Day 1
• Gestational age ≥36 weeks. For children born with gestational age between 32 and 36 weeks, a postmenstrual age of ≥36 weeks is required .
• Signed parent/legal guardian informed consent.

You may not qualify if:

• Cohort 1 :
• Decompensated liver disease, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy
• Patients who were not compliant with study drug treatment or procedures in Study A4250-012
• 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
• Known hypersensitivity to any components of odevixibat
• Cohort 2 :
• Patient with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following:
• Biliary atresia of any kind
• Progressive familial intrahepatic cholestasis (PFIC)
• Benign recurrent intrahepatic cholestasis
• 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
• Patient with past medical history or ongoing chronic diarrhea requiring intravenous fluid or nutritional intervention for treatment of the diarrhea and/or its sequelae
• Patient has a confirmed past diagnosis of infection with human immunodeficiency virus or other present and active, clinically significant chronic infection
• 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
• Cancer diagnosis (except for basal cell carcinoma)

Sponsors & Collaborators

• Albireo, an Ipsen Company: lead

Study Sites (39)

Rady Children's Hospital

San Diego, California, 92123, United States

RECRUITING

UCSF

San Francisco, California, 94158, United States

RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

RECRUITING

Riley Hospital for Children at IU Health

Indianapolis, Indiana, 46202, United States

RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

COMPLETED

Children's Mercy Hospital and Clinics

Kansas City, Missouri, 64018, United States

RECRUITING

Northwell Health System

New Hyde Park, New York, 11042, United States

RECRUITING

Hassenfeld Children's Hospital at NYU Langone

New York, New York, 10016, United States

RECRUITING

New York-Presbyterian / Columbia University Irving Medical Center

New York, New York, 10032, United States

NOT YET RECRUITING

The Childrens Hospital at Montefiore Albert Einstein School of Medicine

The Bronx, New York, 10467, United States

COMPLETED

Atrium Health Carolinas Medical

Durham, North Carolina, 27710, United States

RECRUITING

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

RECRUITING

Oregon Health Science University School of Medicine

Portland, Oregon, 97239, United States

RECRUITING

Monroe Carell Jr. Childrens Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

RECRUITING

Childrens Medical Center of Dallas University of Texas Southwestern

Dallas, Texas, 75207, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Texas Liver Institute

San Antonio, Texas, 78215, United States

RECRUITING

Children's Hospital Queensland

South Brisbane, Queensland, 4101, Australia

NOT YET RECRUITING

The Royal Children's Hospital Melbourne

Parkville, Victoria, 3052, Australia

NOT YET RECRUITING

Cliniques Universitaires Saint-Luc Bruxelles

Brussels, 1200, Belgium

COMPLETED

Hôpital Femme Mère Enfant de Lyon

Bron, 69677, France

TERMINATED

Antenne pediatrique du CIC-Hopital Jeanne De Flandre

Lille, France

COMPLETED

Hopital Necker Enfants Malades

Paris, 75015, France

COMPLETED

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

ACTIVE NOT RECRUITING

Medizinische Hochschul

Hanover, 30625, Germany

ACTIVE NOT RECRUITING

Universitatsklinik fur Kinder-und Jugendmedizin Tubingen

Tübingen, 72076, Germany

COMPLETED

Shaare Zedek Schneider Children Medical

Petah Tikva, Israel

NOT YET RECRUITING

AOU Meyer

Florence, Italy

COMPLETED

Azienda Ospedale University

Padova, 35128, Italy

ACTIVE NOT RECRUITING

Ospedale Pediatrico Bambino Gesu

Rome, 00165, Italy

ACTIVE NOT RECRUITING

University of Malaya Medical Center

Kuala Lumpur, 59100, Malaysia

RECRUITING

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

COMPLETED

Wilhelmina Children's Hospital UMCU Utrecht

Utrecht, Netherlands

COMPLETED

Instytut Pomnik-Centrum Zdrowia Dzieck

Warsaw, 04-730, Poland

ACTIVE NOT RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

NOT YET RECRUITING

Istanbul University Istanbul Medical Faculty Hospital

Istanbul, Turkey (Türkiye)

ACTIVE NOT RECRUITING

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, United Kingdom

RECRUITING

King's College Hospital NHS Foundation Trust King's College Hospital Paediatric Research

London, SE5 9RS, United Kingdom

RECRUITING

MeSH Terms

Conditions

Alagille Syndrome

Interventions

odevixibat

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Central Study Contacts

Ipsen Recruitment enquiries

CONTACT

See e mail; clinical.trials@ipsen.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2021
• First Posted: September 5, 2021
• Study Start: September 3, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: 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.
• Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Locations

BE (1); MY (1); NL (2); DE (3); PL (1); TU (1); GB (2); TW (1); IL (1); IT (3); FR (3); AU (2); US (18)