- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03353454
A Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)
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 Overview
Status
Intervention / Treatment
Study Type
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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:
|
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
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SHP625-306
- 2017-003138-99 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
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Clinical Trials on Maralixibat
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TakedaActive, not recruiting
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Mirum Pharmaceuticals, Inc.RecruitingAlagille SyndromeUnited States
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Mirum Pharmaceuticals, Inc.CompletedProgressive Familial Intrahepatic Cholestasis (PFIC)United States, United Kingdom, Poland, France
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Mirum Pharmaceuticals, Inc.Clinigen, Inc.Approved for marketingAlagille SyndromeUnited States
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Mirum Pharmaceuticals, Inc.Active, not recruitingProgressive Familial Intrahepatic Cholestasis (PFIC)United States, Argentina, France, Singapore, United Kingdom, Belgium, Turkey, Austria, Brazil, Canada, Colombia, Germany, Italy, Lebanon, Mexico, Poland
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Mirum Pharmaceuticals, Inc.CompletedAlagille SyndromeFrance, Belgium, Poland, Australia, Spain, United Kingdom
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Mirum Pharmaceuticals, Inc.Completed
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Mirum Pharmaceuticals, Inc.Lumena Pharmaceuticals, Inc.; Childhood Liver Disease Research and Education...Completed
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Mirum Pharmaceuticals, Inc.CompletedBiliary AtresiaUnited States, United Kingdom, China, Taiwan, Germany, Poland, Singapore, Vietnam