Clinical trial NCT03353454: A Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Progressive Familial Intrahepatic Cholestasis (PFIC)
Keywords: Cholestasis
Maralixibat
Mutation
Lead sponsor: Mirum Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-11-27
Enrollment: 0
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs])
timeFrame: Baseline up to Week 26
Secondary outcomes:
measure: Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs]) and Serum Bile Acids (sBA)
timeFrame: Baseline up to Week 26
measure: Normalization or Reduction From Baseline in Serum Bile Acids (sBA)
timeFrame: Baseline up to Week 26
measure: Change Over Time in Daily Average Itch Reported Outcome (ItchRO[Obs]) Score
timeFrame: Baseline up to Week 26
measure: Change Over Time in Before Midday (AM) Itch Reported Outcome (ItchRO[Obs]) Score
timeFrame: Baseline up to Week 26
measure: Change Over Time in After Midday (PM) Itch Reported Outcome (ItchRO[Obs]) Score
timeFrame: Baseline up to Week 26
measure: Disappearance of Pruritus as Measured by Observer Itch Reported Outcome (ItchRO[Obs])
timeFrame: Baseline up to Week 26
measure: Improvement in Height
timeFrame: Baseline up to Week 26
measure: Improvement in Weight
timeFrame: Baseline up to Week 26
measure: Change From Baseline in Nutritional Status as Measured by Mid-arm Circumference
timeFrame: Baseline, Week 26
measure: Change From Baseline in Nutritional Status as Measured by Triceps Skin Fold
timeFrame: Baseline, Week 26
measure: Change From Baseline in Clinician Scratch Scale (CSS)
timeFrame: Baseline, Week 26
measure: Change From Baseline in Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL)
timeFrame: Baseline, Week 26
measure: Change From Baseline in Quality of Sleep as Measured by Children's Sleep Habits Questionnaire (CSHQ)
timeFrame: Baseline, Week 26
measure: Normalization or Meaningful Reduction From Baseline of Alanine Aminotransferase (ALT)
timeFrame: Baseline up to Week 26
measure: Normalization or Meaningful Decrease From Baseline of Total Bilirubin
timeFrame: Baseline up to Week 26
measure: Change From Baseline in Biomarkers of Bile Acid Synthesis
timeFrame: Baseline, Week 26
measure: Evaluate the safety of SHP625
timeFrame: Baseline up to Week 26
measure: Plasma Levels of Maralixibat Over Time
timeFrame: Baseline, Week 6, 10, 14, 18, 22 and 26
Other outcomes:
Locations:
Study officials:
affiliation: Mirum
name: Study Director
role: STUDY_DIRECTOR
References: