Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03353454
Recruitment Status : Withdrawn (The study was withdrawn due to change of ownership of the study drug maralixibat. Future studies of maralixibat will be posted by Mirum Pharmaceuticals.)
First Posted : November 27, 2017
Last Update Posted : March 18, 2019
Sponsor:
Information provided by (Responsible Party):
Mirum Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE November 14, 2017
First Posted Date  ICMJE November 27, 2017
Last Update Posted Date March 18, 2019
Estimated Study Start Date  ICMJE October 25, 2018
Estimated Primary Completion Date June 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 22, 2017)
Treatment Response as measured by the Observer Itch Reported Outcome (ItchRO(Obs) ™) [ Time Frame: Baseline up to Week 26 ]
Compare the percentage of patients on active treatment vs. placebo who meet response criteria which is defined as improvement in average Observer Itch Reported Outcome (ItchRO(Obs) severity decrease from baseline on at least 2 of the last 3 study visits.
Change History Complete list of historical versions of study NCT03353454 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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%.
  • 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%.
  • 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]).
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2017)
  • Normalization or Reduction From Baseline in Serum Bile Acids (sBA) [ Time Frame: Baseline, Week 26 ]
    Compare the percentage of patients on active treatment vs. placebo with normalization or significant reduction from baseline in serum bile acids
  • Disappearance of Pruritus as Measured by Observer Itch Reported Outcome (ItchRO(Obs) [ Time Frame: Baseline up to Week 26 ]
    Compare the percentage of patients on active treatment vs. placebo of participants who experience disappearance of pruritus as measured by ItchRO(Obs)
  • Change in Patient Itch Reported Outcome Instrument (ItchRO[Pt]) [ Time Frame: Baseline, Week 26 ]
    Change in ItchRO(pt) ™, as completed by participants of appropriate age, will be compared between active treatment and placebo
  • Improvement in Height [ Time Frame: Baseline up to Week 26 ]
    Proportion of participants on active treatment vs. placebo with a height z-score change from baseline >0.
  • Improvement in Weight [ Time Frame: Baseline up to Week 26 ]
    Proportion 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 [ Time Frame: Baseline, Week 26 ]
    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 [ Time Frame: Baseline, Week 26 ]
    Compare the change in nutritional status as measured by triceps skin fold in participants on active treatment vs. placebo
  • Mean 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.
  • 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.
  • 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.
  • Normalization or Meaningful Reduction From Baseline of Alanine Aminotransferase (ALT) [ Time Frame: Baseline up to Week 26 ]
    Proportion of participants whose ALT normalizes on treatment or has decreased ≥50%.
  • Normalization or Meaningful Decrease From Baseline of Total Bilirubin [ Time Frame: Baseline up to Week 26 ]
    Proportion of participants whose total bilirubin normalizes on treatment or has decreased ≥50%.
  • 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])
  • Evaluate the safety of SHP625 [ Time Frame: Baseline, week 26 ]
    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 [ Time Frame: Pre-dose through Week 26 ]
    Systemic concentrations of maralixibat in plasma
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)
Official Title  ICMJE 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)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Progressive Familial Intrahepatic Cholestasis (PFIC)
Intervention  ICMJE
  • Drug: Maralixibat
    Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.
    Other Name: SHP625
  • Drug: Placebo
    Placebo matching to maralixibat orally twice daily for 26 weeks.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Maralixibat
  • Placebo Comparator: Placebo
    Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: February 28, 2019)
0
Original Estimated Enrollment  ICMJE
 (submitted: November 22, 2017)
150
Estimated Study Completion Date  ICMJE June 15, 2020
Estimated Primary Completion Date June 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03353454
Other Study ID Numbers  ICMJE SHP625-306
2017-003138-99 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mirum Pharmaceuticals, Inc.
Study Sponsor  ICMJE Mirum Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Mirum
PRS Account Mirum Pharmaceuticals, Inc.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP