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Trial details
A Placebo-controlled study of Maralixibat in Subjects with Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC)
Current status:
Approved
|
Date registered:
18/06/2020
Trial version(s)
Current: 03/03/2020
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2020063422
Protocol number
MRX-502
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
05/04/2019
Primary sponsor
Mirum Pharmaceuticals Inc
Primary sponsor: Country of origin
California
Public title
A Placebo-controlled study of Maralixibat in Subjects with Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC)
Acronym
N/A
Scientific 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
Acronym
N/A
Brief summary of the study: English
This is a 6-month, international, multicenter, randomized, double-blind, placebo-controlled Phase 3 study in subjects with PFIC. The study will be followed by the long-term extension study MRX-503, during which all subjects who complete study MRX-502 will have the opportunity to be treated with maralixibat. The purpose of this study is to determine if the investigational treatment (maralixibat) is safe and effective in pediatric participants with Progressive Familial Intrahepatic Cholestasis (PFIC).
Brief summary of the study: Arabic
دراسة لمده سته اشهر مرحلة ثالثة عشوائية مزدوجة التعمية محكومة بدواء وهمي لتقييم أمان ماراليكسيبات وفعاليته في علاج المرضى موضوع الدراسة المصابين بمرض الركود الصفراوي العائلي التقدمي داخل الكبد(PFIC)) الهدف منها تحديد اذا كان الدواء ماراليكسابات امن و فعال على المرضى الاطفال ام لا.
Health conditions/problem studied: Specify
Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Subjects with Progressive Familial Intrahepatic Cholestasis (PFIC)
Interventions: Specify
Drug: Maralixibat Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks. Other Name: Formerly LUM001 and SHP625 Other: Placebo Placebo matching to maralixibat orally twice daily for 26 weeks.
Key inclusion and exclusion criteria: Inclusion criteria
Informed consent and assent (as applicable) per Institutional Review Board/Ethics Committee (IRB/EC) 2. Male or female subjects with a body weight ≥ 5 kg, who are ≥12 months and < 18 years of age at time of consent 3. Cholestasis as manifested by total sBA ≥ 3× ULN 4. An average AM ItchRO(Obs) score ≥ 1.5 during 4 consecutive weeks of the screening period, leading to the baseline visit (Visit 1) 5. Completion of at least 21 valid* morning ItchRO(Obs) entries during 4 consecutive weeks of the screening period, leading to the baseline visit (Visit 1) (*valid = completed and not answered as “I don’t know”; maximum allowed invalid reports = 7, no more than 2 invalid reports during the last 7 days before randomization) 6. Diagnosis of PFIC based on the following: Chronic cholestasis as manifested by persistent (>6 months) pruritus, biochemical abnormalities or pathological evidence of progressive liver disease and Primary Cohort: Subjects with genetic testing results consistent with biallelic disease-causing variation in ABCB11 (PFIC2), based on standard of care genotyping Supplemental Cohort: i. Subjects with genetic testing results consistent with biallelic disease-causing variation in ATP8B1 (PFIC1), ABCB4 (PFIC3), or TJP2 (PFIC4), based on standard of care genotyping ii. Subjects with PFIC phenotype without a known mutation or with another known mutation not described above iii. Subjects with PFIC after internal or external biliary diversion surgery or for whom internal or external biliary diversion surgery was reversed 7. Male and females of non-childbearing potential. Males and non-pregnant, non-lactating females of childbearing potential who are sexually active must agree to use acceptable contraception during the study and 30 days following the last dose of the study medication. Females of childbearing potential must have a negative pregnancy test 8. Access to email or phone for scheduled remote visits 9. Ability to read and understand the questionnaires (both caregivers and subjects above the age of assent) 10. Access to consistent caregiver(s) during the study 11. Subject and caregiver willingness to comply with all study visits and requirements
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
1
Key inclusion and exclusion criteria: Age maximum
17
Key inclusion and exclusion criteria: Exclusion criteria
Predicted complete absence of bile salt excretion pump (BSEP) function based on the type of ABCB11 mutation (PFIC2), as determined by a standard of care genotyping (applies to primary cohort only). History of surgical disruption of the enterohepatic circulation (applies to primary cohort only) 3. Chronic diarrhea requiring intravenous fluid or nutritional intervention for the diarrhea and/or its sequelae at screening or during the 6 months prior to screening 4. Previous or planned liver transplant 5. Decompensated cirrhosis (international normalized ratio [INR] > 1.5, albumin < 30 g/L, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy) 6. ALT or total serum bilirubin (TSB) > 15× ULN at screening 7. Presence of other liver disease 8. Presence of any other disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs, including bile salt metabolism in the intestine (e.g., inflammatory bowel disease), per Investigator discretion 9. Liver mass on imaging, including screening ultrasound 10. Known diagnosis of human immunodeficiency virus (HIV) infection 11. Any prior cancer diagnosis (except for in situ carcinoma) within 5 years of the screening visit (Visit 0) 12. Any known history of alcohol or substance abuse 13. Administration of bile acids or lipid binding resins, or sodium phenylbutyrate during the screening period 14. Administration of growth hormones at any time before or during the study 15. Administration of any investigational drug, biologic, or medical device during the screening period 16. Previous use of an ileal bile acid transporter inhibitor (IBATi) 17. History of non-adherence to medical regimens, unreliability, medical condition, mental instability or cognitive impairment that, in the opinion of the Investigator or Sponsor medical monitor, could compromise the validity of informed consent, compromise the safety of the subject, or lead to nonadherence with the study protocol or inability to conduct the study procedures 18. Known hypersensitivity to maralixibat or any of its excipients
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Placebo
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
Maralixibat
Year of authorization
2019
Month of authorization
4
Type of IMP
Others
Type of IMP: Specify
Pharmaceutical – Chemical
Pharmaceutical class
Maralixibat is an inhibitor of the apical sodium-dependent bile acid transporter/ileal bile acid transporter/solute carrier family 10 (sodium/bile acid cotransporter family) member 2 (ASBT/IBAT/SLC10A2), a transmembrane protein localized on the luminal surface of ileal enterocytes.
Therapeutic indication
Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Subjects with Progressive Familial Intrahepatic Cholestasis (PFIC).
Therapeutic benefit
Maralixibat was designed to be minimally absorbed, therefore maximizing the local exposure of the molecule to the receptor and minimizing systemic exposure of the drug and limiting drug-drug interactions and systemic toxicity. These characteristics include a high molecular weight of 740 Da, and the addition of a positively charged quaternary amino moiety that can interact with the negatively charged surface of the enterocyte cell membrane and prevent absorption. Also The pharmacokinetics (PK), safety, and efficacy of maralixibat were assessed in a previous clinical development program that evaluated maralixibat as a potential lipid-lowering agent in patients with hypercholesterolemia. The efficacy and long term safety of maralixibat in the treatment of cholestatic liver disease in pediatric subjects with PFIC) indicate that a subgroup of subjects with PFIC2 experienced clinically significant improvements on maralixibat treatment as manifested by a large reduction or normalization of sBA, reduction in pruritus (ItchRO[Obs]), and normalization of elevated bilirubin, alanine and aspartate aminotransferase (ALT andAST) for those subjects with elevated baseline values.
Biospecimen retention
Samples without DNA
Biospecimen description
Blood Samples
Target sample size
30
Actual enrollment target size
3
Date of first enrollment: Type
Actual
Date of first enrollment: Date
09/07/2019
Date of study closure: Type
Actual
Date of study closure: Date
31/12/2020
Recruitment status
Recruiting
Date of completion
IPD sharing statement plan
Yes
IPD sharing statement description
The Sponsor and/or its representatives accessing the records and data will take all reasonable precautions in accordance with applicable laws, regulations, and guidelines to maintain the confidentiality of subjects’ identities. Subjects are assigned a unique identifying number; however, their initials and date of birth may also be collected, if permitted under local laws governing privacy
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
US NCT
NCT03905330
Sources of Monetary or Material Support
Name
Mirum Pharmaceuticals Inc. 950 Tower LaneFoster City, CA 94404
Secondary Sponsors
Name
N/A
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Chadi
Safa
Beirut
Lebanon
0096171251819
chadi.safa@clinart.net
Clinart
Scientific
Adib
Moukarzel
HDF
Lebanon
009613516060
adib.moukarzel@usj.edu.lb
Hotel Dieu De France
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Hotel Dieu De France
Adib Moukarzel
Gastroenterology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Hotel Dieu de France
01/10/2019
Nancy Choucair Alam
nancy.alam@usj.edu.lb
961 1 421 000 ext 2335
Countries of Recruitment
Name
Lebanon
Argentina
Austria
Belgium
Brazil
Canada
Colombia
France
Germany
Hungary
Italy
Mexico
Poland
Singapore
Turkey
United Kingdom
United States of America
Health Conditions or Problems Studied
Condition
Code
Keyword
Progressive Familial Intrahepatic Cholestasis
Pruritus (L29)
PFIC
Interventions
Intervention
Description
Keyword
Maralixibat Chloride
Inhibitor of the apical sodium-dependent bile acid transporter/ileal bile acid transporter/solute carrier family 10 (sodium/bile acid cotransporter family) member 2 (ASBT/IBAT/SLC10A2)
Maralixibat
Placebo
Placebo contain only the following excipient :lactose monohydrate, microcrystalline methylcellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate.
Placebo
Primary Outcomes
Name
Time points
Measure
To evaluate the efficacy of maralixibat vs placebo on the severity of pruritus in the primary cohort
Normalisation of sBA
PIS, CIS and IchRO
Key Secondary Outcomes
Name
Time points
Measure
To evaluate the efficacy of maralixibat vs. placebo on the frequency of pruritus in the primary cohort
Stop of Pruritis
PIS,CIS and ICHro
To evaluate the efficacy of maralixibat vs. placebo on total serum bile acid (sBA) levels in the primary cohort
Normalisation of sBA
sBA
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial