Evaluation of Maralixibat in Biliary Atresia Response Post-Kasai

Biliary Atresia Clinical Trial

— EMBARK  

Official title:

Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Subjects With Biliary Atresia After Hepatoportoenterostomy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04524390
• Other study ID #: MRX-701
• Status: Completed
• Phase: Phase 2
• Start date: July 8, 2021
• Est. completion date: February 7, 2024

Study information

• Verified date: March 2024
• Source: Mirum Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to evaluate the efficacy and safety of maralixibat in infants with Biliary Atresia (BA) after Hepatoportoenterostomy (HPE, also known as the Kasai procedure).

Description:

This is a double-blind randomized, placebo-controlled study in subjects with Biliary Atresia with a primary endpoint at Week 26 followed by long-term open-label period during which all subjects will receive maralixibat to Week 104.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: February 7, 2024
• Est. primary completion date: November 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Days to 111 Days

Eligibility

Inclusion Criteria:

1. Male or female subjects with body weight =2500 g, who are =21 days old and <90 days old at the time of HPE (Kasai)

2. HPE or Kasai Procedure within 3 weeks prior to randomization

3. Clinical diagnosis of biliary atresia

Exclusion Criteria:

1. Subjects with intractable chronic diarrhea at randomization

2. Subjects not tolerating enteral feeds at randomization

3. History of ileal resection

4. Diagnosis of biliary atresia splenic malformation syndrome or cystic biliary atresia

5. Evidence of another non-biliary atresia pathology involving the intrahepatic bile duct (e.g., paucity, sclerosing cholangitis)

6. Evidence of liver failure (e.g. significant ascites)

Related Conditions & MeSH terms

• Biliary Atresia

Intervention

Drug:
• Maralixibat
A small molecule inhibitor of the ileal bile acid transporter (IBAT)

Other:
• Placebo
Identical to maralixibat except for the active drug substance

Locations

Country	Name	City	State
China	Beijing Pediatric Research Institute	Beijing	Beijing
China	Guangzhou Women and Children's Medical Center	Guangzhou	Guangdong
China	The Children's Hospital, Zhejiang University School of Medicine	Hanzhou	Zhejiang
China	Children's Hospital of Fudan University	Shanghai
China	Children's hospital of Shanghai	Shanghai
Germany	Hannover Medical School	Hanover
Poland	Instytut Pomnik-Centrum Zdrowia Dziecka	Warsaw
Singapore	KK women's and Children's hospital	Bukit Timah
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	King's College Hospital NHS	London
United States	Children's Healthcare of Atlanta - Emory University School of Medicine	Atlanta	Georgia
United States	Montefiore Medical Center	Bronx	New York
United States	Texas Children's Hospital	Houston	Texas
United States	New York-Presbyterian - Columbia University Medical Center	New York	New York
United States	NYU Grossman School of Medicine	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Division of Gastroenterology & Hepatology	Phoenix	Arizona
Vietnam	Vietnam National Children's Hospital	Hanoi
Vietnam	Children's Hospital No. 1	Ho Chi Minh City
Vietnam	Hue Central Hospital	Hu?	Th?a Thiên Hu?

Sponsors (1)

Lead Sponsor	Collaborator
Mirum Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Vietnam,  China,  Germany,  Poland,  Singapore,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in total serum bilirubin levels		From baseline to Week 26
Secondary	Mean change in total serum bile acids		From baseline to Week 26
Secondary	Proportion of participants with mean TSB levels <2 mg/dL through Week 26		From baseline to Week 26
Secondary	Proportion of participants observed to have a liver-related clinical event, including liver transplantation, liver decompensation, discontinuations due to liver related events, or death.	Liver decompensation (hepatic encephalopathy, variceal bleeding, new persistent ascites)	From Baseline to Week 26
Secondary	Proportion of participants undergoing liver transplantation or death through Week 26		From Baseline to Week 26
Secondary	Proportion of participants observed to develop clinically evident portal hypertension defined as splenomegaly and thrombocytopenia (platelet count <150 x 109/L) or clinically evident ascites or endoscopic evidence of esophageal or gastric varices.	Splenomegaly => (spleen size >2 cm below the costal margin palpated on physical examination)	From Baseline to Week 26
Secondary	Proportion of participants with mean TSB levels =1.2 mg/dL		From Baseline to Week 26
Secondary	Proportion of participants with mean sBA levels =40 mmol/L		From Baseline to Week 26