Long-term Safety and Efficacy of Odevixibat in Patients With Alagille Syndrome (ASSERT-EXT)

An Open Label Study to Evaluate the Long-term Safety and Efficacy of Odevixibat (A4250) in Patients With Alagille Syndrome (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.

Study Overview

• Status: Recruiting
• Conditions: Alagille Syndrome
• Intervention / Treatment: Drug: Odevixibat

Detailed Description

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is available provided continued use is supported by the risk-benefit profile, the participant has not been previously withdrawn or discontinued from the study, and the study is not terminated by the Sponsor.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.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ipsen Recruitment enquiries; Phone Number: See e mail; Email: clinical.trials@ipsen.com

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Terminated
      • Children's Hospital Queensland
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Terminated
      • The Royal Children's Hospital Melbourne
• Belgium
  • Brussels, Belgium, 1200
    • Completed
    • Cliniques Universitaires Saint-Luc Bruxelles
• France
  • Bron, France, 69677
    • Terminated
    • Hôpital Femme Mère Enfant de Lyon
  • Lille, France
    • Completed
    • Antenne pediatrique du CIC-Hopital Jeanne De Flandre
  • Paris, France, 75015
    • Completed
    • Hôpital Necker Enfants Malades
• Germany
  • Berlin, Germany, 13353
    • Active, not recruiting
    • Charité - Universitätsmedizin Berlin
  • Hanover, Germany, 30625
    • Active, not recruiting
    • Medizinische Hochschul
  • Tübingen, Germany, 72076
    • Completed
    • Universitatsklinik fur Kinder-und Jugendmedizin Tubingen
• Israel
  • Petah Tikva, Israel
    • Terminated
    • Shaare Zedek Schneider Children Medical
• Italy
  • Florence, Italy
    • Completed
    • AOU Meyer
  • Padova, Italy, 35128
    • Active, not recruiting
    • Azienda Ospedale University
  • Rome, Italy, 00165
    • Active, not recruiting
    • Ospedale Pediatrico Bambino Gesu
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • University of Malaya Medical Center
    • Contact: Yee Siong Chaw; Phone Number: 6017-672-1338; Email: chaw.esther87@gmail.com
    • Principal Investigator: Way Seah Lee
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Completed
    • Universitair Medisch Centrum Groningen
  • Utrecht, Netherlands
    • Completed
    • Wilhelmina Children's Hospital UMCU Utrecht
• Poland
  • Warsaw, Poland, 04-730
    • Active, not recruiting
    • Instytut Pomnik-Centrum Zdrowia Dzieck
• Taiwan
  • Taipei, Taiwan
    • Terminated
    • National Taiwan University Hospital
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye)
    • Active, not recruiting
    • Istanbul University Istanbul Medical Faculty Hospital
• United Kingdom
  • Birmingham, United Kingdom
    • Recruiting
    • Birmingham Women's and Children's NHS Foundation Trust
    • Principal Investigator: Girish Gupte
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • King's College Hospital NHS Foundation Trust King's College Hospital Paediatric Research
    • Contact: Michelle Tran; Phone Number: 7590074458; Email: michelle.tran@nhs.net
    • Principal Investigator: Alastair Baker
• United States
  • California
    • San Diego, California, United States, 92123
      • Recruiting
      • Rady Children's Hospital
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF
      • Principal Investigator: Philip Rosenthal, MD
      • Contact: Joanna Curry; Email: joanna.curry@ucsf.edu
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Children's Healthcare of Atlanta
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Riley Hospital for Children at IU Health
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Trung Van; Phone Number: 410-614-8583; Email: tvan5@jhu.edu
      • Contact: Ashley Thomas; Phone Number: 410-955-9161; Email: ashley_thomas@jhmi.edu
      • Principal Investigator: Wikrom Karnsakul
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Completed
      • Boston Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64018
      • Recruiting
      • Children's Mercy Hospital and Clinics
      • Contact: Heather Wasserkbury; Phone Number: 816-302-9735; Email: hwasserkrug@cmh.edu
      • Principal Investigator: Ryan Fisher
  • New York
    • New Hyde Park, New York, United States, 11042
      • Recruiting
      • Northwell Health System
      • Principal Investigator: Shari Sheflin-Findling
    • New York, New York, United States, 10016
      • Recruiting
      • Hassenfeld Children's Hospital at NYU Langone
      • Principal Investigator: Nadia Ovchinsky, MD
      • Contact: Rozanne Groen; Phone Number: 929-392-4083; Email: rozanne.groen@nyulangone.org
    • New York, New York, United States, 10032
      • Terminated
      • New York-Presbyterian / Columbia University Irving Medical Center
    • The Bronx, New York, United States, 10467
      • Completed
      • The Childrens Hospital at Montefiore Albert Einstein School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Atrium Health Carolinas Medical
      • Principal Investigator: Vani Gopalareddy
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital
      • Principal Investigator: Akihiro Asai
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health Science University School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Monroe Carell Jr. Childrens Hospital at Vanderbilt
  • Texas
    • Dallas, Texas, United States, 75207
      • Recruiting
      • Childrens Medical Center of Dallas University of Texas Southwestern
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Children's Hospital
    • San Antonio, Texas, United States, 78215
      • Recruiting
      • Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Odevixibat (A4250); Capsules for oral administration once daily for 72 weeks.	Drug: Odevixibat; Odevixibat is a small molecule and selective inhibitor of IBAT.; Other Names: A4250

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)	Assessed by the Albireo ObsRO/patient reported outcomes (PRO) instruments	Baseline to week 72 (cohort 1).
Change from baseline in sleep parameters.	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.	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.	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.	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	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).
Change from baseline in serum bile acid levels.		Baseline through 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 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).
Number of participants with change from baseline in physical examination		Baseline to week 72 (cohort 1).
Number of participants with change from baseline in vital signs		Baseline to week 72 (cohort 1).
Change from baseline in concomitant medications		Baseline to week 72 (cohort 1).
Change from baseline in laboratory test results Pharmacokinetic (PK) Cmax [Time Frame: Day 1, Week 4, Week 8, and Week 12]		Baseline to week 72 (cohort 1).
Change from baseline in plasma concentration of study drug		Day 1, Week 4, Week 8, and Week 12 (cohort 1).
Pharmacodynamic Parameters: Change in serum bile acids levels		Baseline to Week 12 (cohort 2).

Collaborators and Investigators

• Sponsor: Albireo, an Ipsen Company
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 13, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Genetic Diseases, Inborn; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Abnormalities, Multiple; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Alagille Syndrome; odevixibat
• Other Study ID Numbers: A4250-015; 2023-509028-17-00 (Ctis); 2021-000996-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing 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.
• IPD Sharing 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/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No