Alagille SyndromePhase 3ASSERT-EXTNCT05035030
Long-term Safety and Efficacy of Odevixibat in Patients With Alagille Syndrome
A Phase 3 study testing Odevixibat in people with Alagille Syndrome, run by Albireo, an Ipsen Company at 35 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Alagille Syndrome
- What is being tested?
- Odevixibat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 35 sitesin 10 countries
- Study dates
- 3 Sep 2021to 15 Feb 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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 :
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- 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.
Who cannot join
- 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 :
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- 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)
- Chronic kidney disease with an impaired renal function and a glomerular filtration rate <70 mL/min/1.73 m2
- Patient with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to the Screening Visit
- Patient has had a liver transplant, or a liver transplant is planned within 6 months of Study Day 1
- Decompensated liver disease, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy
- 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)
- Serum alanine aminotransferase (ALT) >10 × upper limit of normal (ULN) at Screening
- Serum ALT >15 × ULN at any time point during the last 6 months unless an alternate etiology was confirmed for the elevation
- Total bilirubin >15 × ULN at Screening
- 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.
- Patient exposed to alcohol or substance abuse in utero
- Bile acid or lipid binding resins and medications that slow gastrointestinal motility
- 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
- 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
Trial locations and contacts
35 sites in 10 countries.
35 sites in 10 countries
United States18 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30329
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Boston Children's Hospital
Boston, Massachusetts, 02115
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Childrens Medical Center of Dallas University of Texas Southwestern
Dallas, Texas, 75207
Atrium Health Carolinas Medical
Durham, North Carolina, 27710
Texas Children's Hospital
Houston, Texas, 77030
Riley Hospital for Children at IU Health
Indianapolis, Indiana, 46202
Children's Mercy Hospital and Clinics
Kansas City, Missouri, 64018
Monroe Carell Jr. Childrens Hospital at Vanderbilt
Nashville, Tennessee, 37232
Northwell Health System
New Hyde Park, New York, 11042
Hassenfeld Children's Hospital at NYU Langone
New York, New York, 10016
New York-Presbyterian / Columbia University Irving Medical Center
New York, New York, 10032
Oregon Health Science University School of Medicine
Portland, Oregon, 97239
Texas Liver Institute
San Antonio, Texas, 78215
Rady Children's Hospital
San Diego, California, 92123
UCSF
San Francisco, California, 94158
The Childrens Hospital at Montefiore Albert Einstein School of Medicine
The Bronx, New York, 10467
France3 sites
Hôpital Femme Mère Enfant de Lyon
Bron, 69677
Antenne pediatrique du CIC-Hopital Jeanne De Flandre
Lille
Hopital Necker Enfants Malades
Paris, 75015
Germany3 sites
Charité - Universitätsmedizin Berlin
Berlin, 13353
Medizinische Hochschul
Hanover, 30625
Universitatsklinik fur Kinder-und Jugendmedizin Tubingen
Tübingen, 72076
Italy3 sites
AOU Meyer
Florence
Azienda Ospedale University
Padova, 35128
Ospedale Pediatrico Bambino Gesu
Rome, 00165
Netherlands2 sites
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ
Wilhelmina Children's Hospital UMCU Utrecht
Utrecht
United Kingdom2 sites
Birmingham Women's and Children's NHS Foundation Trust
Birmingham
King's College Hospital NHS Foundation Trust King's College Hospital Paediatric Research
London, SE5 9RS
Turkey (Türkiye)1 site
Istanbul University Istanbul Medical Faculty Hospital
Istanbul
About this study
Official title: 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.
Read the 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:
- 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.
- 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.
- 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.
- Conditions
- Alagille Syndrome
- Being tested
- Odevixibat
- Medical subject headings
- Alagille Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OdevixibatDrug
Also called A4250
Odevixibat is a small molecule and selective inhibitor of IBAT.
| Study group | Role | What they receive |
|---|---|---|
| Odevixibat (A4250) | Experimental | Capsules for oral administration once daily for 72 weeks. Receives: Drug: Odevixibat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in pruritus
Assessed as change in scratching score as measured by measured by the Albireo Observer-Reported Outcome Caregiver Instrument.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to week 12 (cohort 2).
Change from baseline in concomitant medications.
Measured: Baseline to week 12 (cohort 2).
Change from baseline in fat-soluble vitamin levels.
Measured: Baseline to week 12 (cohort 2).
Secondary outcomes (16)
Change from baseline in serum bile acids levels
Measured: 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.
Measured: 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
Measured: 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).
Measured: 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.
Measured: 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").
Measured: 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").
Measured: 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").
Measured: Baseline to Weeks 4, 12, 24, 48 and 72 (cohort 1).
Change from baseline in serum bile acid levels.
Measured: 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.
Measured: Baseline to week 72 (cohort 1).
Number of participants with change from baseline in physical examination
Measured: Baseline to week 72 (cohort 1).
Number of participants with change from baseline in vital signs
Measured: Baseline to week 72 (cohort 1).
Change from baseline in concomitant medications
Measured: 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]
Measured: Baseline to week 72 (cohort 1).
Change from baseline in plasma concentration of study drug
Measured: Day 1, Week 4, Week 8, and Week 12 (cohort 1).
Pharmacodynamic Parameters: Change in serum bile acids levels
Measured: Baseline to Week 12 (cohort 2).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study start3 Sep 2021
- Primary completion15 Feb 2027 (estimated)
- Study completion15 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alagille SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albireo, an Ipsen Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05035030
- Sponsor's protocol ID
- A4250-015
- Other IDs
- 2023-509028-17-00, 2021-000996-36, 2023
- Acronym
- ASSERT-EXT
- Status last verified
- Oct 2026
- First submitted
- 13 Aug 2021
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.