Evaluation of Maralixibat in Biliary Atresia Response Post-Kasai

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04524390

Acronym

EMBARK

Enrollment

Registered

2020-08-24

Start date

2021-07-08

Completion date

2024-02-07

Last updated

2025-03-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Biliary Atresia

Keywords

Biliary Atresia, Kasai, Biliary Tract Diseases, Bile Duct Diseases, Congenital Abnormalities

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.

Interventions

DRUGMaralixibat

A small molecule inhibitor of the ileal bile acid transporter (IBAT)

OTHERPlacebo

Identical to maralixibat except for the active drug substance

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

21 Days to 111 Days

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame
Mean Change in Total Serum Bilirubin Levels	From baseline to Week 26

Secondary

Measure	Time frame	Description
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	—
Mean Change in Total Serum Bile Acids	From baseline to Week 26	—
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	—
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)

Countries

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

Participant flow

Recruitment details

A total of 75 participants were enrolled at 19 sites across 8 countries (China, Germany, Poland, Singapore, Taiwan, United Kingdom, United States, and Vietnam).

Pre-assignment details

The screening period starts when informed consent (by the legally authorized representative) is signed. The duration of the screening period is up to 3 weeks, during which all procedures listed for the screening visit in the schedule of assessment must be completed. A total of 77 patients were screened.

Participants by arm

Arm	Count
Double Blind Period - Placebo The double-blind period comprised of 4-8 weeks of dose escalation followed by 18 - 22 weeks of stable dosing treatment.	35
Double Blind - Maralixibat The double-blind period comprised of 4-8 weeks of dose escalation followed by 18 - 22 weeks of stable dosing treatment.	40
Total	75

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Double Blind	Adverse Event	5	3	0
Double Blind	Consent Withdrawal by subject	2	1	0
Double Blind	Disease Progression	0	1	0
Double Blind	Liver Transplant	5	6	0
Open-Label	Adverse Event	0	0	3
Open-Label	Disease Progression	0	0	1
Open-Label	Drug interruption criteria	0	0	1
Open-Label	Liver Transplant	0	0	1
Open-Label	Study Termination by sponsor	0	0	45

Baseline characteristics

Characteristic	Double Blind Period - Placebo	Double Blind - Maralixibat	Total
Age, Customized Infants and toddlers (28 days-23 months)	35 participants	40 participants	75 participants
Race/Ethnicity, Customized Race Asian	28 Participants	31 Participants	59 Participants
Race/Ethnicity, Customized Race More than one race	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Race Not Reported	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Race Other	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Race White	5 Participants	8 Participants	13 Participants
Region of Enrollment China	18 Participants	18 Participants	36 Participants
Region of Enrollment Germany	0 Participants	1 Participants	1 Participants
Region of Enrollment Poland	1 Participants	1 Participants	2 Participants
Region of Enrollment Singapore	0 Participants	1 Participants	1 Participants
Region of Enrollment Taiwan	1 Participants	2 Participants	3 Participants
Region of Enrollment United Kingdom	6 Participants	4 Participants	10 Participants
Region of Enrollment United States	1 Participants	4 Participants	5 Participants
Region of Enrollment Vietnam	8 Participants	9 Participants	17 Participants
Sex: Female, Male Female	15 Participants	21 Participants	36 Participants
Sex: Female, Male Male	20 Participants	19 Participants	39 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 40	0 / 35	0 / 52
other Total, other adverse events	38 / 40	33 / 35	47 / 52
serious Total, serious adverse events	26 / 40	25 / 35	21 / 52

Outcome results

Primary

Mean Change in Total Serum Bilirubin Levels

Time frame: From baseline to Week 26

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Double Blind - Maralixibat	Mean Change in Total Serum Bilirubin Levels	-3.5 mg/dl	Standard Error 0.853
Double Blind - Placebo	Mean Change in Total Serum Bilirubin Levels	-3.11 mg/dl	Standard Error 0.947

p-value: 0.741995% CI: [-2.76, 1.97]MMRM

Secondary

Mean Change in Total Serum Bile Acids

Time frame: From baseline to Week 26

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Double Blind - Maralixibat	Mean Change in Total Serum Bile Acids	-51.19 umol/L	Standard Error 24.436
Double Blind - Placebo	Mean Change in Total Serum Bile Acids	-5.29 umol/L	Standard Error 28.44

p-value: 0.200295% CI: [-116.86, 25.05]MMRM

Secondary