Clinical trial NCT06553768: Evaluation of Maralixibat in Pruritus Associated With General Cholestatic Liver Disease (EXPAND)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cholestatic Liver Disease (Except ALGS, PFIC, PBC and PSC)
Keywords: Pruritus
Cholestatic Liver Disease
Biliary Atresia
Lead sponsor: Mirum Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2024-08-14
Enrollment: 90
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This study will be conducted in multiple sites in North America, Europe, Middle East and South America.

Eligibility criteria: 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 the presence of chronic liver biochemical abnormalities (\>90 days) and/or pathological evidence of progressive liver disease.
4. 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 \[adjustment for body weight is allowed\]).
5. Access to email or telephone for scheduled participant contacts and access to smart phone or tablet for PROs.
6. Ability to read and/or understand the questionnaires (both caregivers and participants ≥9 years of age).
7. For participants ≤18 years of age: Access to consistent caregiver(s) during the study.

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. 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.
3. Decompensated cirrhosis or complications of cirrhosis (e.g., esophageal or gastric variceal bleeding in the last 6 months, high-risk esophageal or gastric varices, ascites, hepatic encephalopathy, hepatorenal syndrome). Patients with compensated cirrhosis with preserved hepatic 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 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.
6. Laboratory results during the screening visit as follows:

   1. Platelet count ≤70,000/mm3. Patients with any condition that further increases bleeding risk are excluded.
   2. Albumin \<30 g/L
   3. INR ≥1.5 (after intravenous or subcutaneous supplementation of vitamin K)
   4. Total bilirubin \>10 mg/dL
   5. ALT \>10× ULN
7. Use of an IBAT inhibitor within 8 weeks prior to the screening visit.
8. Known intolerance/hypersensitivity to maralixibat or its excipients.
9. 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.

Primary outcomes:
measure: Mean change in the ItchRO(Obs) severity score
timeFrame: From baseline to average of week 13 to week 20
Secondary outcomes:
measure: Mean change in total sBA (serum bile acid) level
timeFrame: From baseline to average of week 12 and week 20
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles (CHLA)
state: California
city: Palo Alto
country: United States
facility: Stanford Children's Health in Palo Alto
state: California
city: Chicago
country: United States
facility: Lurie Children's Hospital
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Morgan Stanley Children's Hospital - NewYork Presbyterian
state: New York
city: Morrisville
country: United States
facility: Science 37, Inc (Remote-homebase Telemedicine)
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Brasília
country: Brazil
facility: Hospital de Criança de Brasília (HCB)
city: Porto Alegre
country: Brazil
facility: Hospital da Criança Santo Antonio
city: São Paulo
country: Brazil
facility: Hospital Sírio-Libanês
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Lyon
country: France
facility: Hôpital Femme Mère Enfant
city: Marseille
country: France
facility: Hôpitaux Universitaires de Marseille Timone
city: Paris
country: France
facility: Hôpital Kremlin Bicêtre
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf - Klinik für Kinder- und Jugendmedizin
city: Munich
country: Germany
facility: LMU Klinikum - Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Palermo
country: Italy
facility: ISMETT - Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
city: Beirut
country: Lebanon
facility: Hotel Dieu de France
city: Mexico City
country: Mexico
facility: Hospital Infantil de México Federico Gómez
city: Zapopan
country: Mexico
facility: Consultario de Joshue David Covarrubias Esquer
city: Warsaw
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
Study officials:
References: