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

NCT03353454 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: SHP625-3062017-003138-99
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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)

Keywords

Cholestasis; Maralixibat; Mutation

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline up to Week 26

Secondary Outcomes (18)

• Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs]) and Serum Bile Acids (sBA)

  Baseline up to Week 26

• Normalization or Reduction From Baseline in Serum Bile Acids (sBA)

  Baseline up to Week 26

• Change Over Time in Daily Average Itch Reported Outcome (ItchRO[Obs]) Score

  Baseline up to Week 26

• Change Over Time in Before Midday (AM) Itch Reported Outcome (ItchRO[Obs]) Score

  Baseline up to Week 26

• Change Over Time in After Midday (PM) Itch Reported Outcome (ItchRO[Obs]) Score

  Baseline up to Week 26

Study Arms (2)

Maralixibat (SHP625)

EXPERIMENTAL

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

Drug: Maralixibat

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Maralixibat DRUG

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

Also known as: SHP625

Maralixibat (SHP625)

Placebo DRUG

Placebo matching to maralixibat orally twice daily for 26 weeks.

Placebo

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

MeSH Terms

Conditions

Cholestasis, progressive familial intrahepatic 1; Cholestasis

Interventions

maralixibat

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Study Director

  Mirum

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2017
• First Posted: November 27, 2017
• Study Start: October 25, 2018
• Primary Completion: June 15, 2020
• Study Completion: June 15, 2020
• Last Updated: March 18, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share