Evaluation of Maralixibat in Pruritus Associated With General Cholestatic Liver Disease (EXPAND)

Inclusion Criteria:

1. Informed consent and assent (as applicable)

2. Age ≥6 months at time of baseline visit

3. Diagnosis of cholestatic liver disease with cholestatic pruritus based on thepresence of chronic liver biochemical abnormalities (>90 days) and/or pathologicalevidence of progressive liver disease.

4. If taking antipruritics or ursodeoxycholic acid, the participant has to be on astable dosing regimen (i.e., same dose and frequency in the 30 days prior to thescreening visit and will continue this dosing regimen up to Week 40 [adjustment forbody weight is allowed]).

5. Access to email or telephone for scheduled participant contacts and access to smartphone or tablet for PROs.

6. Ability to read and/or understand the questionnaires (both caregivers andparticipants ≥9 years of age).

7. For participants ≤18 years of age: Access to consistent caregiver(s) during thestudy.

Exclusion Criteria:

Those who meet any of the following criteria are NOT eligible to participate in the study:

1. Diagnosis of ALGS, ICP, PBC, PFIC, or PSC with native liver.

2. Current or recent history (<1 year) of atopic dermatitis or other non-cholestaticdiseases associated with pruritus.

3. History of decompensated cirrhosis or complications of cirrhosis (e.g.,esophageal/gastric varices, ascites, hepatic encephalopathy, hepatorenal syndrome).In patients who have had a liver transplant, this exclusion criterion applies to thepost-transplant period only. Patients with compensated cirrhosis with preservedhepatic synthetic function and absence of complications are eligible.

4. Suspected or proven cholangiocarcinoma or hepatocellular carcinoma.

5. Unstable and/or serious medical disease that is likely to impair the ability toparticipate in all aspects of the study, confound efficacy and/or safetyassessments, or result in substantially shortened life expectancy (e.g., any activemalignancy including hematological malignancy, end-stage heart failure, activeinfection, acute and chronic diarrhea). Exceptionally, previous history ofmalignancy, adequately treated/in remission, that in opinion of investigator andmedical monitor does not impact participant safety and participation in the study,may be allowed.

6. Laboratory results during the screening visit as follows:

7. Platelet count ≤150,000/mm3

8. Albumin <30 g/L

9. INR ≥1.5 (after intravenous or subcutaneous supplementation of vitamin K)

10. Total bilirubin >10 mg/dL

11. ALT >10× ULN

12. Use of an IBAT inhibitor within 8 weeks prior to the screening visit.

13. Known intolerance/hypersensitivity to maralixibat or its excipients.

14. History of nonadherence to medical regimens, unreliability, medical condition,mental instability, or cognitive impairment that, in the opinion of theinvestigator, could compromise the validity of informed consent, compromise thesafety of the participant, or lead to nonadherence with the study protocol orinability to conduct the study procedures.