A Phase 3 Double-blind, Randomized, Placebo-controlled Study of the Safety and Efficacy of Odevixibat (A4250) in Patients with Alagille Syndrome (ASSERT)

1. A male or female patient (of any age) with genetically confirmed diagnosis
of ALGS. A patient may be randomized based on genetic testing results in the
medical record. If genetic testing results are not available, testing will be
performed at Screening Visit 1, and the patient may not be randomized until the
genetic diagnosis is confirmed
2. Patient must have a history of significant pruritus and a caregiver reported
observed scratching or a patient-reported itching score at an average of >=2 (on
0 to 4 scale), as measured by the Albireo ObsRO instrument (for patients <18
years of age) or the PRO instrument (for patients >18 years of age) in the 14
days prior to randomization. For each AM and PM weekly assessment a minimum of
4 out of 7 expected scores must be recorded. The mean of the weekly AM and the
mean of the weekly PM scores will be averaged to determine the pruritus score
as measured by ObsRO or PRO, if the patient is >=18 years of age
3. Patient must have an elevated baseline serum bile acid level. Each of the
serum bile acid levels obtained at Screening Visit 1 and Screening Visit 2 must
be greater than the upper limit of normal (>ULN)
4. Patient and/or legal guardian must sign 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 in order to remain in the study
5. Caregivers must be willing and able to use an eDiary device as required by
the study and patients >=8 years of age must be willing to use an eDiary if able
to do so
6. Sexually active males and females must agree to use a reliable contraceptive
method with <=1% failure rate (such as hormonal contraception, intrauterine
device, or complete abstinence) throughout the duration of the study and 90
days thereafter (from signed informed consent through 90 days after last dose
of study drug).

1. Patient with past medical history or ongoing presence of other types of
liver disease including, but not limited to, the following:
a) Biliary atresia of any kind
b) PFIC
c) Benign recurrent intrahepatic cholestasis
d) Suspected or proven liver cancer or metastasis to the liver on imaging
studies
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 (i.e. >3 months)
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 randomization (Study Day 1) or completion of
oral anti-infective treatment within 2 weeks prior to start of Screening Period
6. Cancer within the last 5 years except for basal cell carcinoma
7. Cancer >5 years prior to screening except for non-liver cancers with no
evidence of recurrence
8. Chronic kidney disease with an impaired renal function and a glomerular
filtration rate <70 mL/min/1.73 m2
9. Patient with surgical history of disruption of the enterohepatic circulation
(biliary diversion surgery) within 6 months prior to start of Screening Period
10. Patient has had a liver transplant or a liver transplant is planned within
6 months of randomization
11. Decompensated liver disease, history or presence of clinically significant
ascites, variceal hemorrhage, and/or encephalopathy
12. INR >1.4 (the patient may be treated with Vitamin K intravenously, and if
INR is <=1.4 at resampling the patient may be randomized)
13. Serum ALT >10 × ULN at Screening
14. Serum ALT >15 × ULN at any time point during the last 6 months unless an
alternate etiology was confirmed for the elevation
15. Total bilirubin >15 × ULN at Screening
16. 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
17. Any patient who is pregnant or lactating or who is planning to become
pregnant within 24 weeks of randomization
18. Patient with a past medical history of alcohol or substance abuse. Patient
must agree to refrain from illicit drug and alcohol use during the study
19. Administration of bile acid or lipid binding resins and medications that
slow gastrointestinal motility
20. Patient has had investigational exposure to a drug, biologic agent, or
medical device within 30 days prior to Screening, or 5 half-lives of the study
agent, whichever is longer
21. 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