Evaluation of Maralixibat in Pruritus Associated With General Cholestatic Liver Disease (EXPAND)
- Conditions
- Cholestatic Liver Disease (Except ALGS, PFIC, PBC and PSC)
- Interventions
- Other: Placebo
- Registration Number
- NCT06553768
- Lead Sponsor
- Mirum Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- Informed consent and assent (as applicable)
- Age ≥6 months at time of baseline visit
- 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.
- 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]).
- Access to email or telephone for scheduled participant contacts and access to smart phone or tablet for PROs.
- 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.
Those who meet any of the following criteria are NOT eligible to participate in the study:
-
Diagnosis of ALGS, ICP, PBC, PFIC, or PSC with native liver.
-
Current or recent history (<1 year) of atopic dermatitis or other non-cholestatic diseases associated with pruritus.
-
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 the post-transplant period only. Patients with compensated cirrhosis with preserved hepatic synthetic function and absence of complications are eligible.
-
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.
-
Laboratory results during the screening visit as follows:
- Platelet count ≤150,000/mm3
- Albumin <30 g/L
- INR ≥1.5 (after intravenous or subcutaneous supplementation of vitamin K)
- Total bilirubin >10 mg/dL
- ALT >10× ULN
-
Use of an IBAT inhibitor within 8 weeks prior to the screening visit.
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 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. Maralixibat Maralixibat Participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 39 weeks.
- Primary Outcome Measures
Name Time Method Mean change in the ItchRO(Obs) severity score From baseline to average of week 13 to week 20 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.
- Secondary Outcome Measures
Name Time Method Mean change in total sBA (serum bile acid) level From baseline to average of week 12 and week 20
Trial Locations
- Locations (32)
Children's Hospital Los Angeles (CHLA)
🇺🇸Los Angeles, California, United States
Stanford Children's Health in Palo Alto
🇺🇸Palo Alto, California, United States
Lurie Children's Hospital
🇺🇸Chicago, Illinois, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
NYU Langone Health
🇺🇸New York, New York, United States
Morgan Stanley Children's Hospital - NewYork Presbyterian
🇺🇸New York, New York, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Hospital de Criança de Brasília (HCB)
🇧🇷Brasília, Brazil
Hospital da Criança Santo Antonio
🇧🇷Porto Alegre, Brazil
Hospital Sírio-Libanês
🇧🇷São Paulo, Brazil
Stollery Children's Hospital
🇨🇦Edmonton, Alberta, Canada
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Hôpital Femme Mère Enfant
🇫🇷Lyon, France
Hôpitaux Universitaires de Marseille Timone
🇫🇷Marseille, France
Hôpital Kremlin Bicêtre
🇫🇷Paris, France
Universitätsklinikum Hamburg Eppendorf - Klinik für Kinder- und Jugendmedizin
🇩🇪Hamburg, Germany
ISMETT - Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione
🇮🇹Palermo, Italy
Hospital Sant Joan de Deu
🇪🇸Barcelona, Spain
LMU Klinikum - Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
🇩🇪Munich, Germany
Ospedale Pediatrico Bambino Gesu
🇮🇹Rome, Italy
Consultario de Joshue David Covarrubias Esquer
🇲🇽Zapopan, Mexico
Azienda Ospedaliera Papa Giovanni XXIII
🇮🇹Bergamo, Italy
Instytut Pomnik Centrum Zdrowia Dziecka
🇵🇱Warsaw, Poland
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hotel Dieu de France
🇱🇧Beirut, Lebanon
Hospital Infantil de México Federico Gómez
🇲🇽Mexico City, Mexico
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom