A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC) (MARCH-PFIC)
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|ClinicalTrials.gov Identifier: NCT03905330|
Recruitment Status : Completed
First Posted : April 5, 2019
Last Update Posted : October 27, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Progressive Familial Intrahepatic Cholestasis (PFIC)||Drug: Maralixibat Other: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||93 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official 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|
|Actual Study Start Date :||July 9, 2019|
|Actual Primary Completion Date :||September 1, 2022|
|Actual Study Completion Date :||September 1, 2022|
Participants will be randomized to Maralixibat oral solution (up to 600 microgram per kilogram [mcg/kg]) orally twice daily for 26 weeks.
Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.
Other Name: Formerly LUM001 and SHP625
Placebo Comparator: Placebo
Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
Placebo matching to maralixibat orally twice daily for 26 weeks.
- Mean change in the average morning ItchRO(Obs) severity score in the primary cohort. [ Time Frame: Between Baseline and Week 15 through Week 26 ]
- Mean change in total sBA level. [ Time Frame: Between Baseline and Week 18 through Week 26 ]
- Mean change in the average morning ItchRO(Obs) severity score in participants with all PFIC subtypes. [ Time Frame: Between Baseline and Week 15 through Week 26 ]
- Proportion of ItchRO(Obs) responders. [ Time Frame: Between Baseline and Week 15 to Week 26 ]
- Proportion of sBA responders. [ Time Frame: Between Baseline and Week 18 to Week 26 ]
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|Ages Eligible for Study:||1 Year to 17 Years (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Informed consent and assent (as applicable) per Institutional Review Board/Ethics Committee (IRB/EC)
- Male or female subjects with a body weight ≥5 kg, who are ≥12 months and <18 years of age at time of baseline
- Cholestasis as manifested by total sBA ≥3× ULN (applies to primary cohort only)
- An average AM ItchRO(Obs) score ≥1.5 during 4 consecutive weeks of the screening period, leading to the baseline visit (Visit 1)
- 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)
Diagnosis of PFIC based on the following:
- Chronic cholestasis as manifested by persistent (>6 months) pruritus in addition to biochemical abnormalities and/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 standardofcare 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 standardofcare genotyping. ii. Subjects with PFIC phenotype without a known mutation or with another known mutation not described above or with intermittent cholestasis as manifested by fluctuating sBA levels. iii. Subjects with PFIC after internal or external biliary diversion surgery or for whom internal or external biliary diversion surgery was reversed.
- 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 methods of 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
- Access to email or phone for scheduled remote visits
- Ability to read and understand the questionnaires (both caregivers and subjects above the age of assent)
- Access to consistent caregiver(s) during the study
- Subject and caregiver willingness to comply with all study visits and requirements.
- Predicted complete absence of bile salt excretion pump (BSEP) function based on the type of ABCB11 mutation (PFIC2), as determined by a standardofcare genotyping (applies to primary cohort only). Subjects can enter the study in the Supplemental Cohort (under inclusion criteria 6.ii or 6.iii).
- Recurrent intrahepatic cholestasis, indicated by a history of sBA levels <3x ULN or intermittent pruritus (applies to primary cohort only)
- Current or recent history (<1 year) of atopic dermatitis or other non-cholestatic diseases associated with pruritus.
- History of surgical disruption of the enterohepatic circulation (applies to primary cohort only)
- 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
- Previous or need for imminent liver transplant
- Decompensated cirrhosis (international normalized ratio [INR] >1.5, albumin <30 g/L, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy)
- ALT or total serum bilirubin (TSB) >15× ULN at screening
- Presence of other liver disease
- 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
- Possibly malignant liver mass on imaging, including screening ultrasound
- Known diagnosis of human immunodeficiency virus (HIV) infection
- Any prior cancer diagnosis (except for in situ carcinoma) within 5 years of the screening visit (Visit 0)
- Any known history of alcohol or substance abuse
- Administration of bile acids or lipid binding resins, or phenylbutyrates during the screening period
- Criterion has been deleted as of Amendment 3
- Administration of any investigational drug, biologic, or medical device during the screening period
- Previous use of an ileal bile acid transporter inhibitor (IBATi)
- 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
- Known hypersensitivity to maralixibat or any of its excipients.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03905330
|Responsible Party:||Mirum Pharmaceuticals, Inc.|
|Other Study ID Numbers:||
2019-001211-22 ( EudraCT Number )
|First Posted:||April 5, 2019 Key Record Dates|
|Last Update Posted:||October 27, 2022|
|Last Verified:||October 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases