Back to resultsA Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)
Primary Purpose
Progressive Familial Intrahepatic Cholestasis (PFIC)
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Maralixibat
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Progressive Familial Intrahepatic Cholestasis (PFIC) focused on measuring Cholestasis, Maralixibat, Mutation
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Maralixibat (SHP625)
Placebo
Arm Description
Participants will be randomized to Maralixibat oral solution (up to 600 microgram per kilogram [mcg/kg]) orally twice daily for 26 weeks.
Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs]) and Serum Bile Acids (sBA)
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.
Normalization or Reduction From Baseline in Serum Bile Acids (sBA)
Compare the percentage of participants on active treatment vs. placebo with normalization or significant reduction from baseline in sBA.
Change Over Time in Daily Average Itch Reported Outcome (ItchRO[Obs]) Score
Change over time in daily average ItchRO scores will be reported.
Change Over Time in Before Midday (AM) Itch Reported Outcome (ItchRO[Obs]) Score
Change over time in AM ItchRO scores will be reported.
Change Over Time in After Midday (PM) Itch Reported Outcome (ItchRO[Obs]) Score
Change over time in PM ItchRO scores will be reported.
Disappearance of Pruritus as Measured by Observer Itch Reported Outcome (ItchRO[Obs])
Compare the percentage of participants on active treatment vs. placebo of participants who experience disappearance of pruritus as measured by ItchRO(Obs).
Improvement in Height
Number of participants on active treatment vs. placebo with a height z-score change from baseline >0.
Improvement in Weight
Number of participants on active treatment vs. placebo with a weight z-score change from baseline >0.
Change From Baseline in Nutritional Status as Measured by Mid-arm Circumference
Compare the change in nutritional status as measured by mid-arm circumference in participants on active treatment vs. placebo.
Change From Baseline in Nutritional Status as Measured by Triceps Skin Fold
Compare the change in nutritional status as measured by triceps skin fold in participants on active treatment vs. placebo.
Change From Baseline in Clinician Scratch Scale (CSS)
Compare the change in Clinician Scratch Scale score in participants on active treatment vs. placebo.
Change From Baseline in Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL)
Compare the change from baseline of PedsQL in participants on active treatment vs. placebo.
Change From Baseline in Quality of Sleep as Measured by Children's Sleep Habits Questionnaire (CSHQ)
Compare the change from baseline of CSHQ in participants on active treatment vs. placebo.
Normalization or Meaningful Reduction From Baseline of Alanine Aminotransferase (ALT)
Number of participants whose ALT normalizes on treatment or has decreased >=50%.
Normalization or Meaningful Decrease From Baseline of Total Bilirubin
Number of participants whose total bilirubin normalizes on treatment or has decreased >=50%.
Change From Baseline in Biomarkers of Bile Acid Synthesis
Change from baseline in biomarkers of bile acid synthesis (serum 7 alpha-hydroxy-4-cholesten-3-one [C4]).
Evaluate the safety of SHP625
Adverse events, changes in vital signs, laboratory, and other safety parameters will be compared between participants on active treatment vs. placebo.
Plasma Levels of Maralixibat Over Time
Systemic concentrations of maralixibat in plasma will be assessed.
Full Information
NCT ID
NCT03353454
First Posted
November 14, 2017
Last Updated
March 14, 2019
Sponsor
Mirum Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03353454
Brief Title
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
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Withdrawn
Why Stopped
The study was withdrawn due to change of ownership of the study drug maralixibat. Future studies of maralixibat will be posted by Mirum Pharmaceuticals.
Study Start Date
October 25, 2018 (Anticipated)
Primary Completion Date
June 15, 2020 (Anticipated)
Study Completion Date
June 15, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirum Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Familial Intrahepatic Cholestasis (PFIC)
Keywords
Cholestasis, Maralixibat, Mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Maralixibat (SHP625)
Arm Type
Experimental
Arm Description
Participants will be randomized to Maralixibat oral solution (up to 600 microgram per kilogram [mcg/kg]) orally twice daily for 26 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
Intervention Type
Drug
Intervention Name(s)
Maralixibat
Other Intervention Name(s)
SHP625
Intervention Description
Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matching to maralixibat orally twice daily for 26 weeks.
Primary Outcome Measure Information:
Title
Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs])
Description
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.
Time Frame
Baseline up to Week 26
Secondary Outcome Measure Information:
Title
Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs]) and Serum Bile Acids (sBA)
Description
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.
Time Frame
Baseline up to Week 26
Title
Normalization or Reduction From Baseline in Serum Bile Acids (sBA)
Description
Compare the percentage of participants on active treatment vs. placebo with normalization or significant reduction from baseline in sBA.
Time Frame
Baseline up to Week 26
Title
Change Over Time in Daily Average Itch Reported Outcome (ItchRO[Obs]) Score
Description
Change over time in daily average ItchRO scores will be reported.
Time Frame
Baseline up to Week 26
Title
Change Over Time in Before Midday (AM) Itch Reported Outcome (ItchRO[Obs]) Score
Description
Change over time in AM ItchRO scores will be reported.
Time Frame
Baseline up to Week 26
Title
Change Over Time in After Midday (PM) Itch Reported Outcome (ItchRO[Obs]) Score
Description
Change over time in PM ItchRO scores will be reported.
Time Frame
Baseline up to Week 26
Title
Disappearance of Pruritus as Measured by Observer Itch Reported Outcome (ItchRO[Obs])
Description
Compare the percentage of participants on active treatment vs. placebo of participants who experience disappearance of pruritus as measured by ItchRO(Obs).
Time Frame
Baseline up to Week 26
Title
Improvement in Height
Description
Number of participants on active treatment vs. placebo with a height z-score change from baseline >0.
Time Frame
Baseline up to Week 26
Title
Improvement in Weight
Description
Number of participants on active treatment vs. placebo with a weight z-score change from baseline >0.
Time Frame
Baseline up to Week 26
Title
Change From Baseline in Nutritional Status as Measured by Mid-arm Circumference
Description
Compare the change in nutritional status as measured by mid-arm circumference in participants on active treatment vs. placebo.
Time Frame
Baseline, Week 26
Title
Change From Baseline in Nutritional Status as Measured by Triceps Skin Fold
Description
Compare the change in nutritional status as measured by triceps skin fold in participants on active treatment vs. placebo.
Time Frame
Baseline, Week 26
Title
Change From Baseline in Clinician Scratch Scale (CSS)
Description
Compare the change in Clinician Scratch Scale score in participants on active treatment vs. placebo.
Time Frame
Baseline, Week 26
Title
Change From Baseline in Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL)
Description
Compare the change from baseline of PedsQL in participants on active treatment vs. placebo.
Time Frame
Baseline, Week 26
Title
Change From Baseline in Quality of Sleep as Measured by Children's Sleep Habits Questionnaire (CSHQ)
Description
Compare the change from baseline of CSHQ in participants on active treatment vs. placebo.
Time Frame
Baseline, Week 26
Title
Normalization or Meaningful Reduction From Baseline of Alanine Aminotransferase (ALT)
Description
Number of participants whose ALT normalizes on treatment or has decreased >=50%.
Time Frame
Baseline up to Week 26
Title
Normalization or Meaningful Decrease From Baseline of Total Bilirubin
Description
Number of participants whose total bilirubin normalizes on treatment or has decreased >=50%.
Time Frame
Baseline up to Week 26
Title
Change From Baseline in Biomarkers of Bile Acid Synthesis
Description
Change from baseline in biomarkers of bile acid synthesis (serum 7 alpha-hydroxy-4-cholesten-3-one [C4]).
Time Frame
Baseline, Week 26
Title
Evaluate the safety of SHP625
Description
Adverse events, changes in vital signs, laboratory, and other safety parameters will be compared between participants on active treatment vs. placebo.
Time Frame
Baseline up to Week 26
Title
Plasma Levels of Maralixibat Over Time
Description
Systemic concentrations of maralixibat in plasma will be assessed.
Time Frame
Baseline, Week 6, 10, 14, 18, 22 and 26
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Mirum
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)
We'll reach out to this number within 24 hrs