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

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
Drug: Placebo
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.
Drug: Maralixibat
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mirum Pharmaceuticals, Inc.

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 25, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 15, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 15, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 14, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 22, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 27, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 18, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 14, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

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