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

NCT ID: NCT03353454

Last Updated: 2019-03-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-25
• Study Completion Date: 2020-06-15

Brief Summary

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).

Conditions

Progressive Familial Intrahepatic Cholestasis (PFIC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Maralixibat (SHP625)

Participants will be randomized to Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) orally twice daily for 26 weeks.

Group Type: EXPERIMENTAL

Maralixibat

Intervention Type: DRUG

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

Placebo

Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching to maralixibat orally twice daily for 26 weeks.

Interventions

Maralixibat

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

Intervention Type: DRUG

Placebo

Placebo matching to maralixibat orally twice daily for 26 weeks.

Intervention Type: DRUG

Other Intervention Names

SHP625

Eligibility Criteria

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.

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.

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mirum Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Mirum

Other Identifiers

2017-003138-99

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SHP625-306

Identifier Type: -

Identifier Source: org_study_id