EMBARK Evaluation of Maralixibat BiliaryAtresia Response post Kasai
Research type
Research Study
Full 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
IRAS ID
287291
Contact name
Lara Longpre
Contact email
Sponsor organisation
Mirum Pharmaceutical Inc.
Eudract number
2020-000974-22
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 1 months, 16 days
Research summary
Summary of Research: The EMBARK Study is a 2-phase trial to assess the safety and effectiveness of maralixibat in infants with biliary atresia who have recently undergone Hepatoportoenterostomy (HPE) surgery, also known as the Kasai procedure.
Biliary atresia is a rare liver disease affecting infants in which a blockage occurs in the ducts that carry bile from the liver to the gallbladder. It presents shortly after birth and can lead to various complications related to bile flow and liver damage. Biliary atresia is the leading cause of liver transplant in children worldwide.
To be eligible for the study, patients must be aged at least 21 days but less than 90 days old at the time of HPE/Kasai surgery. Surgery must be performed within 3 weeks of the start of study treatment and patients must be at least 31 days old at this time.
The first phase of the EMBARK Study will be a double-blind period, where the participants will receive either maralixibat or placebo for a period of 26 weeks. Participants will then proceed to the open-label extension (OLE) period of the study, where all patients will receive maralixibat. Participants will continue in the OLE until they become eligible for a long term maralixibat study, the drug is commercially available, the sponsor stops the program or the study doctor decides to the discontinue the child from the trial.
Maralixibat is a grape flavoured oral solution that will be administered to the child twice a day. More than 1600 individuals have received maralixibat, including more than 120 children with other types of liver disease. Maralixibat may be able to help to reduce the amount of bile acids in a child’s blood, helping prevent liver damage and the need for future liver transplant.
This trial will be conducted in NHS sites within Paediatric departments.
Summary of Results: Plain Language Summary of Clinical Study Results
Mirum Pharmaceuticals
Short Study Title:
Study to Assess the Efficacy and Safety of Maralixibat in the Treatment of Biliary Atresia after Hepatoportoenterostomy (EMBARK Study)
Study Medicine:
Maralixibat (compared with placebo)
Study Identifier:
MRX-701
Date of Summary:
28 March 2025
Mirum Pharmaceuticals, the sponsor, thanks the children (and their parents/caregivers) who took part in this clinical study.
Overview
Infant participants in this study received either maralixibat or placebo (neither the parent/caregiver nor doctor knew which treatment was being given) for up to 26 weeks after their hepatoportoenterostomy (HPE) procedure. This was followed by treatment with maralixibat for all participants, whether they received maralixibat or placebo in the first part of the study, for up to 78 weeks.
Bilirubin levels decreased in the blood for both the maralixibat and placebo groups after the HPE procedure. There was more of a decrease in the maralixibat group, but the difference didn’t meet the level of importance that was set for the study.
The two most common side effects related to maralixibat were diarrhea and increased liver enzymes in the blood.
There were no new safety risks identified in the study.
Reason for Doing the Study
Biliary atresia (BA) is a rare liver disease in infants where the ducts in the liver that drain bile to the intestine are blocked or absent. Bile helps digest fats in the diet. When the bile ducts are blocked, bile builds up in the liver instead and causes liver damage.
The hepatoportoenterostomy procedure (HPE, or sometimes called Kasai) is a surgery to go around the blockage and allow the bile to flow from the liver into the intestine. In many cases, this helps the liver work better and delays the need for a liver transplant, but it is not a cure.
Approximately half of all infants with BA who have had HPE will need a liver transplant before reaching 2 years old. There are currently no approved medicines to treat BA. Bilirubin is a waste substance produced by the breakdown of red blood cells. If bilirubin levels in a person’s blood are high, this is a sign that their liver is not working and may speed up the need for a transplant.
Maralixibat is a drug that has been shown to reduce bilirubin levels in the blood (total serum bilirubin) in participants with other liver diseases similar to BA. Maralixibat is not currently approved to treat BA. This study was done to see if maralixibat could work in participants with BA immediately after receiving HPE.
The main question in this study was:
Is maralixibat better than placebo at reducing bilirubin levels after 26 weeks of treatment? A placebo looks like the investigational medicine but does not contain any active ingredients. The treatment was blinded (neither the parent/caregiver nor doctor knew which treatment was being given).
Who Took Part in this Study?
Text Box 2, Textbox
A total of 75 infants joined the study and were randomly (by chance, like flipping a coin) placed into 1 of 2 groups during the first 26 weeks:
40 received maralixibat
35 received placebo
The average age of participants when they started the study was 76 days, and their ages ranged from 41 to 109 days.
Sex and race of participants are shown in the pie charts below:
Picture 2, Picture Picture 3, Picture
How Long Did the Study Last?
The study started in July 2021 and ended in February 2024.
Where Was the Study Done?
Most participants were in Asian countries (76%); other participants were in Europe (17%) or the United States of America (7%).
What Were the Treatments in the Study?
Maralixibat was given as a liquid by mouth. The amount given was based on the participant’s weight. The drug was diluted in water.
The placebo looked like the maralixibat liquid so that the participant’s caregiver and doctor could not tell them apart.
A total of 40 infants received maralixibat and 35 received placebo during the first 26 weeks of the study.
Overall, 64 infants received maralixibat in the study. This includes those who were on placebo during the first 26 weeks of the study who then received maralixibat in the extension period.
What Were the Main Results of the Study?
There was a screening period to check whether participants could enter the study. Then, participants were randomly (by chance, like flipping a coin) assigned to receive either placebo or maralixibat. This was called the double-blind period (neither the parent/caregiver nor doctor knew which treatment was being given during this period).
During the double-blind period, the dose of study medicine (maralixibat or placebo) was based on body weight. The dose was increased during the first 4 to 8 weeks and then maintained at a stable dose through Week 26.
All participants could then receive maralixibat for 78 more weeks in a part of the study called the open-label extension period. In this part of the study, all participants received maralixibat, whether they had previously received placebo or maralixibat in the first part (the doubleblind period) of the study. Participants received standard treatment for BA as well as maralixibat.
For the main analysis, bilirubin levels in the blood decreased (in other words, they improved) slightly more with maralixibat treatment than with placebo. However, the difference between the groups did not meet the level of importance that was set for the study.
Chart 1, Chart element
What Medical Problems Were Reported as Possibly Related to the Study Treatment?
This section is a summary of the medical problems that the participants experienced during this study that the doctors reported as possibly being related to study treatment. These medical problems are called adverse reactions.
The websites listed at the end of this summary may have other information about adverse reactions or medical problems that happened during the study.
The safety of every participant is important during the development of new medicines. The study doctors keep a record of symptoms and adverse reactions that the participants have during the study. These records are used to identify medical problems associated with treatments and to take steps to ensure patient safety and prevent similar occurrences in other patients.
The table below shows how many infants had adverse reactions during the study that were considered to be possibly related to study treatment (maralixibat or placebo).
Number of Participants Who Had Related Adverse Reactions During the Study
Treatment Period
Entire Study Overall (Treatment Period plus Extension Period)
Maralixibat Group
(Out of 40 Participants)
Placebo Group
(Out of 35 Participants)
Maralixibat Group
(Out of 64 Participants)
How many participants had adverse reactions?
9 (23%)
9 (26%)
17 (27%)
How many participants had serious adverse reactions?
3 (8%)
2 (6%)
3 (5%)
The table below shows the most common adverse reactions that were considered related to study medicine during this study and that happened in more than 1 participant.
Related Adverse Reactions That Happened in More Than 1 Participant
Treatment Period
Entire Study Overall (Treatment Period plus Extension Period)
Maralixibat Group
(Out of 40 Participants)
Placebo Group
(Out of 35 Participants)
Maralixibat Group
(Out of 64 Participants)
Diarrhea
7 (18%)
4 (11%)
13 (20%)
Increased alanine aminotransferase (liver enzyme in the blood)
2 (5%)
4 (11%)
2 (3%)
What Were the Serious Adverse Reactions?
An adverse reaction is considered serious when it is life-threatening, causes lasting problems, requires hospital care, or results in death. Diarrhea was the only treatment-related serious adverse reaction that occurred in more than 1 participant: it occurred in 2 (3%) of the 64 participants taking maralixibat.
What Has This Study Added to What is Known About the Disease?
The study has helped the researchers learn more about the safety of maralixibat in infants with BA.
This summary shows only the main results of this study. Other studies may show new information.
Further studies of maralixibat in infants with BA are not planned by Mirum Pharmaceuticals. Maralixibat is not currently approved for the treatment of BA.
REC name
South Central - Hampshire A Research Ethics Committee
REC reference
20/SC/0400
Date of REC Opinion
23 Apr 2021
REC opinion
Further Information Favourable Opinion