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

NCT06553768 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: MRX-8022024-511287-85-00
• Study Type: interventional
• Target: 90
• Locations: 10 countries
• Sites: 24

Brief Summary

The purpose of this study is to determine whether the investigational treatment (maralixibat) is safe and effective in pediatric and adult participants who have cholestatic liver disease with pruritus that has been refractory to other therapies, and who have no other treatment options.

Conditions

Cholestatic Liver Disease (Except ALGS, PFIC, PBC and PSC)

Keywords

Pruritus; Cholestatic Liver Disease; Biliary Atresia

Outcome Measures

Primary Outcomes (1)

• Mean change in the ItchRO(Obs) severity score

  ItchRO(Obs) severity score = Itch Reported Outcome Observer assessment severity score; scale between 0 (not itchy at all) and 4 (extremely itchy); the lower the score the better.

  From baseline to average of week 13 to week 20

Secondary Outcomes (1)

• Mean change in total sBA (serum bile acid) level

  From baseline to average of week 12 and week 20

Study Arms (2)

Maralixibat

EXPERIMENTAL

Participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 39 weeks.

Drug: Maralixibat

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matched to maralixibat oral solution orally once daily for 1 week and then twice daily for 19 weeks. After 20 weeks, participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 19 weeks.

Other: Placebo

Interventions

Maralixibat DRUG

Maralixibat will be provided as an oral solution along with 0.5-, 1.0-, and 3.0-mL sized dosing dispensers. During the double-blind dose escalation period (4 weeks), the study drug (maralixibat) will be administered once daily for 1 week and then twice daily (BID; morning and evening). During the double-blind stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the double-blind dose-escalation period) of maralixibat. During the open-label dose escalation period (4 weeks), all participants will receive maralixibat treatment once daily for 1 week and then twice daily (BID; morning and evening). During the open-label stable dosing period (at least 16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the open-label dose-escalation period) of maralixibat.

Also known as: Formerly LUM001, SHP625

Maralixibat

Placebo OTHER

Placebo matched to maralixibat will be provided as an oral solution along with 0.5-, 1.0-, and 3.0-mL sized dosing dispensers. During the double-blind dose escalation period (4 weeks), study drug will be administered once daily for 1 week and then twice daily (BID; morning and evening). During the double-blind stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the double-blind dose-escalation period) of study drug. During the open-label dose escalation period (4 weeks), all participants will receive maralixibat treatment once daily for 1 week and then twice daily (BID; morning and evening). During the open-label stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the open-label dose-escalation period) of maralixibat.

Placebo

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent and assent (as applicable)
• Age ≥6 months at time of baseline visit
• Diagnosis of a rare cholestatic liver disease with cholestatic pruritus based on the following:
• Chronic liver biochemical abnormalities (\>90 days) and/or pathological evidence of progressive liver disease. Total sBA \>2× ULN is required.
• Persistent pruritus (\>90 days). An average worst-daily (morning and evening) ItchRO(Obs)/ItchRO(Pt) score ≥1.5 during the 2 consecutive weeks of the screening period leading to the baseline visit. If both instruments are administered, a score ≥1.5 is required only for ItchRO(Obs).
• Participants with the following rare diseases will be enrolled in the study:
• Any rare cholestatic liver disease associated with persistent cholestatic pruritus, including but not limited to the following: alpha-1 antitrypsin deficiency, ARC syndrome, BA, Caroli's disease, ciliopathies, hepatic sarcoidosis, idiopathic amyloidosis, IgG4-related sclerosing cholangitis, ischemic cholangiopathy, metabolic or genetic cholestatic liver diseases (e.g., bile acid synthesis defects, defects of bile acid transport or disorders such as transaldolase deficiency, where chronic cholestasis and pruritus are present), secondary sclerosing cholangitis.
• Completion of at least 10 valid daily (morning and evening) ItchRO(Obs)/ItchRO(Pt) entries during 2 consecutive weeks of the screening period, leading to the baseline visit. Each week should have at least 4 valid daily (morning and evening) entries. If both instruments are administered, the completion criterion is required only for ItchRO(Obs).
• If taking antipruritics or ursodeoxycholic acid, the participant has to be on a stable dosing regimen (i.e., same dose and frequency in the 30 days prior to the screening visit and will continue this dosing regimen up to Week 40 \[adjustment for body weight is allowed\]).
• Non-pregnant, non-lactating females of childbearing potential who are sexually active must agree to use at least an acceptable effective method of contraception during the study. Females of childbearing potential must have a negative pregnancy test result.
• Access to email or telephone for scheduled participant contacts and access to smart phone or tablet for PROs (Exception: Participants who do not use a smart phone or tablet because of cultural restrictions will complete the PROs on paper.)
• Ability to read and/or understand the questionnaires (both caregivers and participants ≥9 years of age)
• For participants ≤18 years of age: Access to consistent caregiver(s) during the study
• Willingness (participant or caregiver) to comply with all study visits and requirements through the end of the study

You may not qualify if:

• Those who meet any of the following criteria are NOT eligible to participate in the study:
• Patient Characteristics
• Diagnosis of ALGS, ICP, PBC, PFIC, or PSC
• Active atopic dermatitis or other non-cholestatic diseases associated with pruritus that are not controlled by standard treatment and that may interfere with the severity assessment of cholestasis-associated pruritus
• Suspected or proven cholangiocarcinoma or hepatocellular carcinoma
• Unstable and/or serious medical disease that is likely to impair the ability to participate in all aspects of the study, confound efficacy and/or safety assessments, or result in substantially shortened life expectancy (e.g., any active malignancy including hematological malignancy, end-stage heart failure, active infection, acute and chronic diarrhea). Exceptionally, previous history of malignancy, adequately treated/in remission, that in opinion of investigator and medical monitor does not impact participant safety and participation in the study, may be allowed. The investigator should contact the medical monitor to discuss these cases and seek approval before the screening period.
• Laboratory results during the screening visit as follows:
• Platelet count \<70,000/mm3
• Patients with any condition that further increases bleeding risk (e.g., recent clinically relevant bleeding event \[6 months\], recent major surgery \[12 weeks\], anticoagulant use, platelet function disorders) are excluded.
• Albumin \<30 g/L
• INR ≥1.5 (after intravenous or subcutaneous supplementation of vitamin K)
• Total bilirubin: For participants \<18 years of age: total bilirubin \>10 mg/dL For participants ≥18 years of age: total bilirubin ≥3× ULN
• ALT: For participants \<18 years of age: ALT \>10× ULN For participants ≥18 years of age: ALT \>5× ULN
• Presence of any other disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, including bile salt metabolism in the intestine (e.g., clinically relevant inflammatory bowel disease involving the terminal ileum), per investigator discretion
• History of liver transplant Prior/Concomitant Therapy

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (24)

Children's Hospital Los Angeles (CHLA)

Los Angeles, California, 90027, United States

Location

Stanford Children's Health in Palo Alto

Palo Alto, California, 94304, United States

Location

Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Morgan Stanley Children's Hospital - NewYork Presbyterian

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Hospital de Criança de Brasília (HCB)

Brasília, Brazil

Location

Hospital da Criança Santo Antonio

Porto Alegre, Brazil

Location

Hospital Sírio-Libanês

São Paulo, Brazil

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Hôpitaux Universitaires de Marseille Timone

Marseille, 13005, France

Location

Hôpital Kremlin Bicêtre

Paris, France

Location

Universitätsklinikum Hamburg Eppendorf - Klinik für Kinder- und Jugendmedizin

Hamburg, Germany

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

ISMETT - Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione

Palermo, 90127, Italy

Location

Ospedale Pediatrico Bambino Gesu

Rome, 00165, Italy

Location

Hotel Dieu de France

Beirut, Lebanon

Location

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, Poland

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

King's College Hospital NHS Foundation Trust

London, United Kingdom

Location

Related Links

• Mirum Pharmaceuticals homepage

MeSH Terms

Conditions

Cholangitis, Sclerosing; Pruritus; Biliary Atresia

Interventions

maralixibat

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2024
• First Posted: August 14, 2024
• Study Start: October 14, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1); PL (1); IT (3); US (9); BR (3); DE (1); FR (2); CA (1); ES (2); GB (1)