A Placebo-controlled study of Maralixibat in Subjects with PFIC
Research type
Research Study
Full title
MRX-502: Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Subjects with Progressive Familial Intrahepatic Cholestasis (PFIC) – MARCH-PFIC
IRAS ID
266069
Contact name
Richard Thompson
Contact email
Eudract number
2019-001211-22
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
119916, IND
Duration of Study in the UK
1 years, 10 months, 17 days
Research summary
Summary of Research
Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease that primarily affects children. PFIC taken word for word means:
Progressive: tending to get worse over time;
Familial: passed down to a child from the parents by way of the genes;
Intrahepatic: involves disease inside the liver;
Cholestasis: means poor bile flow and retention of substances in the liver that would normally be excreted into bile.
PFIC is associated with short life expectancy and devastating consequences on patients’ quality of life. There is currently no approved treatment for PFIC and available medical approaches have limited efficacy.
The proposed MARCH study is a multicentre, randomised, double blind, placebo controlled study which is to evaluate the efficacy and safety of study medicine called Maralixibat.
Maralixibat is an investigational medicine (not yet approved by regulatory authorities) which will be given to patients twice a day in the form of oral solution. If the study medicine works as expected, it may help to reduce patients’ PFIC symptoms and pruritus (itching).
Patients between ≥12 months and < 18 years of age with confirmed PFIC diagnosis, who meet all study eligibility criteria can participate in the study.
Patient’s participation will last for approx. 33 weeks and will consist of 4 parts: screening period (up to 6 weeks), Dose Escalation period (4–6 weeks), Stable Dosing period (20–22 weeks) and Safety Follow-up period. Patients will be required to come to the study centre approx. 10 times. Additionally patients will be contacted via phone or email to check on how they are feeling.
Patients will be randomised in a 1:1 ratio to the maralixibat or placebo (look alike treatment without active ingredient) treatment groups.
During the study patients will undergo assessments which will include blood, urine tests, electrocardiogram (ECG), liver ultrasound and questionnaires.Summary of Results
Maralixibat demonstrated statistically significant and clinically meaningful improvements in pruritus severity and serum bile acids in the primary and Progressive Familial Intrahepatic Cholestasis (PFIC) cohorts. Improvements in exploratory endpoints including direct bilirubin, total bilirubin, sleep, fatigue, and growth (weight z-score) were demonstrated in the PFIC cohort participants who received maralixibat. These improvements were all statistically significantly different from placebo in favor of maralixibat. In addition, maralixibat was shown to be well tolerated and demonstrated an acceptable safety profile; the most common treatment emergent Adverse Events in this study were gastrointestinal related, in line with the known mechanism of action. Taken together, the efficacy and safety findings from this study support an overall favorable benefit/risk assessment for maralixibat.
REC name
London - Hampstead Research Ethics Committee
REC reference
19/LO/1428
Date of REC Opinion
29 Oct 2019
REC opinion
Further Information Favourable Opinion