A Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)

Mirum Pharmaceuticals, Inc.

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Conditions

Progressive Familial Intrahepatic Cholestasis (PFIC)

Interventions

MaralixibatDRUG

Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.

PlaceboDRUG

Placebo matching to maralixibat orally twice daily for 26 weeks.

Eligibility

Sex: ALLMax age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Informed consent and assent (as applicable for participants less than or equal to (\<=) 18 years per Institutional Review Board/Ethics Committee (IRB)/Ethics Committee (EC) as appropriate. * Male or female participants between the ages of 12 months and 18 years inclusive (primary cohort) or birth to 18 years inclusive (exploratory cohort) at time of consent, with a body weight greater than or equal to (\>=) 5 kilogram (kg). * Cholestasis as manifested by total sBA greater than (\>) 3\*upper limit of normal (ULN) * An average AM ItchRO(Obs) score \>= 1.5 during the 4 weeks leading to the baseline visit * Diagnosis of PFIC based on: a. Primary cohort: i. Participants with 2 documented mutant alleles in ABCB11 (PFIC2); participants without bile salt export pump (BSEP) function (biallelic truncating mutations in ABCB11) will not be enrolled into the primary cohort. b. Exploratory cohort: i. Participants with PFIC1/3/4 or PFIC2 with biallelic truncating mutationsiii.Infants from birth to \<12 months of age with PFIC ii. Participants with PFIC after internal or external (eg, PEBD) biliary diversion surgery with unsatisfactory pruritus control or where biliary diversion was reversed. Key Exclusion Criteria: * Chronic diarrhea requiring intravenous fluid or nutritional intervention for the diarrhea and/or its sequelae. * History of surgical disruption of the enterohepatic circulation (applies to primary cohort only). * Liver transplant * Decompensated cirrhosis (international normalized ratio \[INR\] \>1.5, albumin \<30 gram per liter \[g/L\], history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy). * ALT \>15\*ULN at screening. * History or presence of other liver disease. * History or 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 (example \[eg\], inflammatory bowel disease), per investigator discretion. * Liver mass on imaging * Known diagnosis of human immunodeficiency virus (HIV) infection. * Any prior cancer diagnosis except for in situ carcinoma or cancers treated within 5 years of the screening visit (Visit 0) with no evidence of recurrence.

Outcomes

Primary Outcomes

Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs])

Compare the percentage of participants on active treatment versus (vs.) placebo who meet response criteria which is defined as improvement in before midday (AM) Observer Itch Reported Outcome (ItchRO\[Obs\]) severity decrease from baseline demonstrated on at least 2 of the last 3 study visits.