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Trial record 1 of 1 for:    NCT03905330
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A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC) (MARCH-PFIC)

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ClinicalTrials.gov Identifier: NCT03905330
Recruitment Status : Recruiting
First Posted : April 5, 2019
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
Mirum Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE April 1, 2019
First Posted Date  ICMJE April 5, 2019
Last Update Posted Date November 23, 2020
Actual Study Start Date  ICMJE July 9, 2019
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2019)
Treatment response as measured by the mean change in pruritus severity as assessed by the Observer rated Itch Reported Outcome (ItchRO [Obs]) [ Time Frame: Between Baseline and Week 15 through 26 ]
Compare the average before midday (AM) Observer Itch Reported Outcome (ItchRO[Obs]) pruritus severity score between participants on active treatment versus placebo
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2019)
  • Treatment response as measured by the mean change in pruritus frequency as assessed by the Observer rated Itch Reported Outcome (ItchRO [Obs]) [ Time Frame: Between Baseline and Week 15 through 26 ]
    Compare the average before midday (AM) Observer Itch Reported Outcome (ItchRO[Obs]) pruritus frequency score between participants on active treatment versus placebo
  • Mean change in total serum Bile Acids [ Time Frame: Between Baseline and Week 26 ]
    Compare normalization or reduction in total serum Bile Acids between participants on active treatment versus placebo
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC)
Official Title  ICMJE MRX-502: Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC) - MARCH-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 This study will be conducted at multiple sites in North America, Europe, Asia, and South America.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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: Formerly LUM001 and SHP625
  • Other: Placebo
    Placebo matching to maralixibat orally twice daily for 26 weeks.
Study Arms  ICMJE
  • Experimental: Maralixibat
    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: Other: 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 4, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Informed consent and assent (as applicable) per Institutional Review Board/Ethics Committee (IRB/EC)
  • Male or female subjects with a body weight ≥ 5.0 kg, who are ≥ 12 months and < 18 years of age at time of consent
  • Cholestasis as manifested by total sBA ≥ 3× Upper Limit of Normal (ULN)
  • An average AM ItchRO(Obs) score ≥ 1.5 during 4 consecutive weeks of the screening period, leading to the baseline visit (Visit 1)
  • Completion of at least 21 valid morning ItchRO(Obs) entries during 4 consecutive weeks of the screening period, leading to the baseline visit (Visit 1)
  • Diagnosis of PFIC based on:

    • Chronic cholestasis as manifested by persistent (>6 months) pruritus, biochemical abnormalities or pathological evidence of progressive liver disease and
    • Primary Cohort: Subjects with genetic testing results consistent with biallelic disease-causing variation in ABCB11 (PFIC2), based on standard of care genotyping
    • Supplemental Cohort: i. Subjects with genetic testing results consistent with biallelic disease-causing variation in ATP8B1 (PFIC1), ABCB4 (PFIC3), or TJP2 (PFIC4), based on standard of care genotyping ii. Subjects with PFIC phenotype without a known mutation or with another known mutation not described above iii. Subjects with PFIC after internal or external biliary diversion surgery or for whom internal or external biliary diversion surgery was reversed

Exclusion Criteria:

  • Predicted complete absence of bile salt excretion pump (BSEP) function based on the type of ABCB11 mutation (PFIC2), as determined by a standard of care genotyping (applies to primary cohort only). Subjects can enter the study in the Supplemental Cohort (under inclusion criteria 6.ii or 6.iii).
  • Recurrent intrahepatic cholestasis, indicated by a history of sBA levels <3x ULN or intermittent pruritus
  • Current or recent history (<1 year) of atopic dermatitis or other non-cholestatic diseases associated with pruritus
  • History of surgical disruption of the enterohepatic circulation (applies to primary cohort only)
  • Chronic diarrhea requiring intravenous fluid or nutritional intervention for the diarrhea and/or its sequelae at screening or during the 6 months prior to screening
  • Previous or need for imminent liver transplant
  • Decompensated cirrhosis (international normalized ratio [INR] > 1.5, and/or albumin < 30 g/L, history or presence of clinically significant ascites, and/or variceal hemorrhage, and/or encephalopathy)
  • Alanine aminotransferase (ALT) or total serum bilirubin (TSB) > 15× ULN at screening
  • Presence of other liver disease
  • 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 (e.g., inflammatory bowel disease), per Investigator discretion
  • Possibly malignant liver mass on imaging, including screening ultrasound
  • Known diagnosis of human immunodeficiency virus (HIV) infection
  • Any prior cancer diagnosis (except for in situ carcinoma) within 5 years of the screening visit (Visit 0)
  • Any known history of alcohol or substance abuse
  • Administration of bile acids or lipid binding resins, or sodium phenylbutyrate during the screening period
  • Administration of growth hormones at any time before or during the study
  • Administration of any investigational drug, biologic, or medical device during the screening period
  • Previous use of an ileal bile acid transporter inhibitor (IBATi)
  • History of non-adherence to medical regimens, unreliability, medical condition, mental instability or cognitive impairment that, in the opinion of the Investigator or Sponsor medical monitor, could compromise the validity of informed consent, compromise the safety of the subject, or lead to nonadherence with the study protocol or inability to conduct the study procedures.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials Mirum +16506674085 clinicaltrials@mirumpharma.com
Contact: Medinfo Mirum medinfo@mirumpharma.com
Listed Location Countries  ICMJE Argentina,   Austria,   Belgium,   Brazil,   Canada,   Colombia,   France,   Germany,   Hungary,   Italy,   Lebanon,   Mexico,   Poland,   Singapore,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03905330
Other Study ID Numbers  ICMJE MRX-502
2019-001211-22 ( 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 Not Provided
PRS Account Mirum Pharmaceuticals, Inc.
Verification Date October 2020

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