Evaluation of Maralixibat in Biliary Atresia Response Post-Kasai

Phase 2

Completed

• Conditions: Biliary Atresia
• Interventions: Drug: Maralixibat; Other: Placebo

• Registration Number: NCT04524390
• Lead Sponsor: Mirum Pharmaceuticals, Inc.

Brief 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).

Detailed 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.

Study Timeline

• Study First Submitted: 2020-08-20
• Study First Submitted QC: 2020-08-20
• Study First Posted: 2020-08-24
• Study Start: 2021-07-08
• Primary Completion: 2023-11-07
• Study Completion: 2024-02-07
• Results First Submitted: 2024-12-20
• Status Verified: 2025-02
• Results First Submitted QC: 2025-02-12
• Results First Posted: 2025-02-17
• Last Update Submitted: 2025-03-10
• Last Update Posted: 2025-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Double Blind - Maralixibat	Maralixibat	The double-blind period comprised of 4-8 weeks of dose escalation followed by 18 - 22 weeks of stable dosing treatment, after which participants were transferred to the open-label arm.
Double Blind - Placebo	Placebo	The double-blind period comprised of 4-8 weeks of dose escalation followed by 18 - 22 weeks of stable dosing treatment, after which participants were transferred to the open-label arm.
Open Label - Maralixibat	Maralixibat	The Open-Label period comprised of 4-8 weeks of dose escalation followed by 70 - 74 weeks of stable dosing treatment. During the OLE, all participants, regardless of treatment assignment in the double-blind period, received maralixibat.

Primary Outcome Measures

Name	Time	Method
Mean Change in Total Serum Bilirubin Levels	From baseline to Week 26

Secondary Outcome Measures

Name	Time	Method
Mean Change in Total Serum Bile Acids	From baseline to Week 26
Proportion of Participants With Mean TSB Levels <2 mg/dL Through Week 26	From baseline to Week 26
Proportion of Participants Observed to Have a Liver-related Clinical Event Transplantation, Liver Decompensation, Discontinuations Due to Liver Related Events, or Death.	From Baseline to Week 26	Liver decompensation (hepatic encephalopathy, variceal bleeding, new persistent ascites)
Proportion of Participants Undergoing Liver Transplantation or Death	From Baseline to Week 26
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.	From Baseline to Week 26	Splenomegaly =\> (spleen size \>2 cm below the costal margin palpated on physical examination)
Proportion of Participants With Mean TSB Levels ≤1.2 mg/dL	From Baseline to Week 26
Proportion of Participants With Mean sBA Levels ≤40 mmol/L	From Baseline to Week 26

Trial Locations

Locations (22)

Vietnam National Children's Hospital; 🇻🇳 Hanoi, Vietnam

Children's Hospital of Fudan University; 🇨🇳 Shanghai, China

The Children's Hospital, Zhejiang University School of Medicine; 🇨🇳 Hanzhou, Zhejiang, China

Children's hospital of Shanghai; 🇨🇳 Shanghai, China

Beijing Pediatric Research Institute; 🇨🇳 Beijing, Beijing, China

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

King's College Hospital NHS; 🇬🇧 London, United Kingdom

Children's Hospital No. 1; 🇻🇳 Ho Chi Minh City, Vietnam

Children's Healthcare of Atlanta - Emory University School of Medicine; 🇺🇸 Atlanta, Georgia, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

NYU Grossman School of Medicine; 🇺🇸 New York, New York, United States

New York-Presbyterian - Columbia University Medical Center; 🇺🇸 New York, New York, United States

Guangzhou Women and Children's Medical Center; 🇨🇳 Guangzhou, Guangdong, China

Hannover Medical School; 🇩🇪 Hanover, Germany

KK women's and Children's hospital; 🇸🇬 Bukit Timah, Singapore

Instytut Pomnik-Centrum Zdrowia Dziecka; 🇵🇱 Warsaw, Poland

Birmingham Children's Hospital; 🇬🇧 Birmingham, United Kingdom

Linkou Chang Gung Memorial Hospital; 🇨🇳 Taoyuan, Taiwan

Hue Central Hospital; 🇻🇳 Huế, Thừa Thiên Huế, Vietnam

Phoenix Children's Division of Gastroenterology & Hepatology; 🇺🇸 Phoenix, Arizona, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States