Cholestatic Liver Disease (Except ALGS, PFIC, PBC and PSC)Phase 3NCT06553768
Evaluation of Maralixibat in Pruritus Associated With General Cholestatic Liver Disease (EXPAND)
A Phase 3 study testing Maralixibat in people with Cholestatic Liver Disease (Except ALGS, PFIC, PBC and PSC), run by Mirum Pharmaceuticals, Inc. at 23 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Cholestatic Liver Disease (Except ALGS, PFIC, PBC and PSC)
- What is being tested?
- Maralixibat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 23 sitesin 10 countries
- Study dates
- 14 Oct 2024to 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 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
- Decompensated cirrhosis or complications of cirrhosis (e.g., esophageal or gastric variceal bleeding in the last 6 months, high-risk esophageal or gastric varices [e.g., large, coiled, occupying >1/3 of the esophageal lumen, red varices or red signs], ascites, hepatic encephalopathy, hepatorenal syndrome). Patients with compensated cirrhosis with preserved hepatic synthetic function (see Exclusion Criterion #6) and absence of complications are eligible.
- Suspected or proven cholangiocarcinoma or hepatocellular carcinoma
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- 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
- Use of an IBAT inhibitor within 8 weeks prior to the screening visit
- Use of any other investigational medication within 30 days or 5 times the half-life, whichever is greater, prior to the screening visit Other Exclusions
- Pregnant or nursing
- Known intolerance/hypersensitivity to maralixibat or its excipients
- History of nonadherence to medical regimens, unreliability, medical condition, mental instability, or cognitive impairment that, in the opinion of the investigator, could compromise the validity of informed consent, compromise the safety of the participant, or lead to nonadherence with the study protocol or inability to conduct the study procedures
- Clinically relevant alcohol use disorder or drug abuse within 12 weeks of screening:
- Moderate alcohol consumption as defined for this study by >1 and >2 standard drinks on average per day for women and men, respectively, within 12 weeks prior to the screening visit. A standard drink is defined as 44 mL (1.5 oz, one shot) of liquor, 148 mL (5 oz) of nonfortified wine, or 355 mL (12 oz) of beer (1 oz=29.57 mL; NIAAA)
- Drug abuse within the 12 weeks prior to, or a positive drug screening result at, the screening visit unless it can be explained by a drug prescription. A positive drug screen will exclude participants if the investigator deems the result to be reflective of a pattern of behavior that might impair the participant's ability to participate in the study.
- Use of cannabinoids (legal, prescribed, or otherwise) is allowed, provided use is stable (including as-needed use without need for increased frequency of use) for ≥12 weeks prior to the screening visit and throughout the entire study duration.
Trial locations and contacts
23 sites in 10 countries.
23 sites in 10 countries
United States8 sites
Lurie Children's Hospital
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Baylor College of Medicine
Houston, Texas, 77030
Children's Hospital Los Angeles (CHLA)
Los Angeles, California, 90027
NYU Langone Health
New York, New York, 10016
Morgan Stanley Children's Hospital - NewYork Presbyterian
New York, New York, 10032
Stanford Children's Health in Palo Alto
Palo Alto, California, 94304
University of Utah
Salt Lake City, Utah, 84112
Brazil3 sites
Hospital de Criança de Brasília (HCB)
Brasília
Hospital da Criança Santo Antonio
Porto Alegre
Hospital Sírio-Libanês
São Paulo
Italy3 sites
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, 24127
ISMETT - Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione
Palermo, 90127
Ospedale Pediatrico Bambino Gesu
Rome, 00165
France2 sites
Hôpitaux Universitaires de Marseille Timone
Marseille, 13005
Hôpital Kremlin Bicêtre
Paris
Spain2 sites
Hospital Universitario Vall d'Hebron
Barcelona
Hospital Universitario La Paz
Madrid
Germany1 site
Universitätsklinikum Hamburg Eppendorf - Klinik für Kinder- und Jugendmedizin
Hamburg
United Kingdom1 site
King's College Hospital NHS Foundation Trust
London
About this study
Official title: Randomized Double-Blind Placebo-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Participants With Cholestatic Pruritus
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.
Read the detailed description
This study will be conducted in multiple sites in North America, Europe, Middle East and South America.
- Being tested
- Maralixibat, Placebo
- Keywords
- Pruritus, Cholestatic Liver Disease, Biliary Atresia
- Medical subject headings
- Cholangitis, Sclerosing, Pruritus, Biliary Atresia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MaralixibatDrug
Also called Formerly LUM001, SHP625
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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Maralixibat | Experimental | Participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 39 weeks. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to average of week 13 to week 20
Secondary outcomes (1)
Mean change in total sBA (serum bile acid) level
Measured: From baseline to average of week 12 and week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2024
- Study start14 Oct 2024
- Primary completionOct 2026 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cholestatic Liver Disease (Except ALGS, PFIC, PBC and PSC)Studies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mirum Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06553768
- Sponsor's protocol ID
- MRX-802
- Other IDs
- 2024-511287-85-00
- Status last verified
- Oct 2026
- First submitted
- 8 Aug 2024
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No