Clinical study to evaluate the Efficacy and Safety of Maralixibat used in treatment of Biliary Atresia subjects after Hepatoportoenterostomy
- Conditions
- Biliary atresia (BA) is a rare, inflammatory condition of the biliary tree that presents in the first weeks of life and leads to bile duct obstruction and consequent liver injury, fibrosis and cirrhosis which lead to portal hypertension and a decline in hepatic synthetic function. Untreated, the outcome of BA is uniformly fatal. The 2 most important improvements in the care of BA patients to date are the Kasai hepatoportoenterostomy (HPEKasai procedure) and orthotopic liver transplantation.MedDRA version: 20.0Level: LLTClassification code 10004653Term: Biliary atresiaSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2020-000974-22-PL
- Lead Sponsor
- Mirum Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 72
1.Informed consent (by the legally authorized representative) per the Institutional Review Board/Independent Ethics Committee (EC)
2.Male or female participants with a body weight =2500 g (before or
during the
screening period) who are =21 days old and <90 days old at the time of HPE or Kasai procedure
3.Gestational age =36 weeks at birth (Those with gestational age <36 weeks with no present clinical or developmental preterm complications that could impact participation in the study may be included after evaluation and approval by the Medical Monitor).
4.HPE or Kasai Procedure within 3 weeks prior to randomization
5.Clinical diagnosis of BA at laparotomy (with subsequent confirmation on histology of the biliary remnant)
6.Caregiver willingness to comply with all study visits and requirements, including ability to read and understand the questionnaires and, if applicable, capable of diluting study medication per investigator training and written instructions
7.Caregiver access to email or phone for remote participant contacts
Are the trial subjects under 18? yes
Number of subjects for this age range: 72
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.Chronic diarrhea requiring ongoing IV fluid or nutritional intervention at screening, during the screening period, or during the 30 days prior to screening
2.History of surgical disruption of the enterohepatic circulation other than HPE
3.Has had any of the following: HPE performed by laparoscopy,
undergone a second HPE, or has undergone an exploratory bile duct
procedure
4.Not tolerating enteral feeds at screening or during the screening period
5.Evidence of another pathology involving the intrahepatic bile ducts (e.g., paucity, sclerosing cholangitis)
6.Diagnosis of polysplenia syndrome, including evidence of BA splenic malformation syndrome, or major malformation of another organ system
7.Diagnosis of cystic BA (based on clinician judgment, including but not limited to ultrasonography and cholangiography results)
8.Decompensated cirrhosis (international normalized ratio [INR] >1.5 after correction of possible vitamin K deficiency, history or presence of clinically significant ascites, known varices, variceal hemorrhage, and/or encephalopathy)
9.Previous or imminent need for liver transplantation
10.Known hypersensitivity to maralixibat or any of its excipients
11.Previous use of an IBAT inhibitor, N-acetyl cysteine,
immunoglobulins, or traditional or herbal medicine remedies that are
used to treat liver diseases or with a safety profile known to impact liver
parameters
12.Receipt of investigational drug, biologic, or medical device within 30 days or 5 half-lives (whichever is longer) prior to screening
13.Treatment with other medications containing propylene glycol (PG) or alcohol or any substrate for alcohol dehydrogenase (e.g., ethanol). For participants <1 month of age only.
14.Known caregiver history of unreliability, mental instability, or cognitive impairment that, in the opinion of the investigator or sponsor medical monitor, 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
15.Presence of other significant liver disease or any other conditions or abnormalities which, in the opinion of the investigator or sponsor medical monitor, may compromise the safety of the participant or interfere with participation in or completion of the study (prior or
current cytomegalovirus infection is allowed)
16.History or 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., inflammatory bowel disease), per investigator discretion
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: •To evaluate the efficacy of maralixibat on biliary drainage after hepatoportoenterostomy (HPE) in participants with BA;Secondary Objective: Secondary Objectives and Endpoints of the Double-Blind Period-<br>• To evaluate the rate of clinically relevant reductions in cholestatic <br>biomarkers with maralixibat treatment.<br>• To evaluate the rate of liver-related clinical events.<br>• To evaluate the safety, tolerability, and pharmacokinetics of <br>maralixibat.<br><br>Open-Label Extension Objectives and Endpoints-<br>• To assess all of the above primary and secondary objectives analyzed <br>over the full study duration, including the open-label extension period;Primary end point(s): Primary Efficacy Endpoint:<br>• Mean change in total serum bilirubin levels from baseline through Week 26 ;Timepoint(s) of evaluation of this end point: - From baseline through Week 26
- Secondary Outcome Measures
Name Time Method