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

March 14, 2019 updated by: Mirum Pharmaceuticals, Inc.

Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat (SHP625) in the Treatment of Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)

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 Overview

Study Type

Interventional

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Experimental: Maralixibat (SHP625)
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 Names:
  • SHP625

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs])
Time Frame: Baseline up to Week 26
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs]) and Serum Bile Acids (sBA)
Time Frame: Baseline up to Week 26
Compare the percentage of participants on active treatment versus (vs.) placebo who meet response criteria which is defined as improvement in average before midday (AM) Observer Itch Reported Outcome (ItchRO[Obs]) severity decrease from baseline and normalization or reduction from baseline sBA demonstrated on at least 2 of the last 3 study visits.
Baseline up to Week 26
Normalization or Reduction From Baseline in Serum Bile Acids (sBA)
Time Frame: Baseline up to Week 26
Compare the percentage of participants on active treatment vs. placebo with normalization or significant reduction from baseline in sBA.
Baseline up to Week 26
Change Over Time in Daily Average Itch Reported Outcome (ItchRO[Obs]) Score
Time Frame: Baseline up to Week 26
Change over time in daily average ItchRO scores will be reported.
Baseline up to Week 26
Change Over Time in Before Midday (AM) Itch Reported Outcome (ItchRO[Obs]) Score
Time Frame: Baseline up to Week 26
Change over time in AM ItchRO scores will be reported.
Baseline up to Week 26
Change Over Time in After Midday (PM) Itch Reported Outcome (ItchRO[Obs]) Score
Time Frame: Baseline up to Week 26
Change over time in PM ItchRO scores will be reported.
Baseline up to Week 26
Disappearance of Pruritus as Measured by Observer Itch Reported Outcome (ItchRO[Obs])
Time Frame: Baseline up to Week 26
Compare the percentage of participants on active treatment vs. placebo of participants who experience disappearance of pruritus as measured by ItchRO(Obs).
Baseline up to Week 26
Improvement in Height
Time Frame: Baseline up to Week 26
Number of participants on active treatment vs. placebo with a height z-score change from baseline >0.
Baseline up to Week 26
Improvement in Weight
Time Frame: Baseline up to Week 26
Number of participants on active treatment vs. placebo with a weight z-score change from baseline >0.
Baseline up to Week 26
Change From Baseline in Nutritional Status as Measured by Mid-arm Circumference
Time Frame: Baseline, Week 26
Compare the change in nutritional status as measured by mid-arm circumference in participants on active treatment vs. placebo.
Baseline, Week 26
Change From Baseline in Nutritional Status as Measured by Triceps Skin Fold
Time Frame: Baseline, Week 26
Compare the change in nutritional status as measured by triceps skin fold in participants on active treatment vs. placebo.
Baseline, Week 26
Change From Baseline in Clinician Scratch Scale (CSS)
Time Frame: Baseline, Week 26
Compare the change in Clinician Scratch Scale score in participants on active treatment vs. placebo.
Baseline, Week 26
Change From Baseline in Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL)
Time Frame: Baseline, Week 26
Compare the change from baseline of PedsQL in participants on active treatment vs. placebo.
Baseline, Week 26
Change From Baseline in Quality of Sleep as Measured by Children's Sleep Habits Questionnaire (CSHQ)
Time Frame: Baseline, Week 26
Compare the change from baseline of CSHQ in participants on active treatment vs. placebo.
Baseline, Week 26
Normalization or Meaningful Reduction From Baseline of Alanine Aminotransferase (ALT)
Time Frame: Baseline up to Week 26
Number of participants whose ALT normalizes on treatment or has decreased >=50%.
Baseline up to Week 26
Normalization or Meaningful Decrease From Baseline of Total Bilirubin
Time Frame: Baseline up to Week 26
Number of participants whose total bilirubin normalizes on treatment or has decreased >=50%.
Baseline up to Week 26
Change From Baseline in Biomarkers of Bile Acid Synthesis
Time Frame: Baseline, Week 26
Change from baseline in biomarkers of bile acid synthesis (serum 7 alpha-hydroxy-4-cholesten-3-one [C4]).
Baseline, Week 26
Evaluate the safety of SHP625
Time Frame: Baseline up to Week 26
Adverse events, changes in vital signs, laboratory, and other safety parameters will be compared between participants on active treatment vs. placebo.
Baseline up to Week 26
Plasma Levels of Maralixibat Over Time
Time Frame: Baseline, Week 6, 10, 14, 18, 22 and 26
Systemic concentrations of maralixibat in plasma will be assessed.
Baseline, Week 6, 10, 14, 18, 22 and 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 25, 2018

Primary Completion (Anticipated)

June 15, 2020

Study Completion (Anticipated)

June 15, 2020

Study Registration Dates

First Submitted

November 14, 2017

First Submitted That Met QC Criteria

November 22, 2017

First Posted (Actual)

November 27, 2017

Study Record Updates

Last Update Posted (Actual)

March 18, 2019

Last Update Submitted That Met QC Criteria

March 14, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Other Study ID Numbers

  • SHP625-306
  • 2017-003138-99 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Progressive Familial Intrahepatic Cholestasis (PFIC)

Clinical Trials on Maralixibat

Subscribe