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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)

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: NCT03905330
Recruitment Status : Active, not recruiting
First Posted : April 5, 2019
Last Update Posted : August 16, 2022
Sponsor:
Information provided by (Responsible Party):
Mirum Pharmaceuticals, Inc.

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).

Condition or disease Intervention/treatment Phase
Progressive Familial Intrahepatic Cholestasis (PFIC) Drug: Maralixibat Other: Placebo Phase 3

Detailed Description:
This study will be conducted at multiple sites in North America, Europe, Asia, and South America.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 9, 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022


Arm Intervention/treatment
Experimental: Maralixibat
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 Name: Formerly LUM001 and SHP625

Placebo Comparator: Placebo
Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
Other: Placebo
Placebo matching to maralixibat orally twice daily for 26 weeks.




Primary Outcome Measures :
  1. Mean change in the average morning ItchRO(Obs) severity score in the primary cohort. [ Time Frame: Between Baseline and Week 15 through Week 26 ]

Secondary Outcome Measures :
  1. Mean change in total sBA level. [ Time Frame: Between Baseline and Week 18 through Week 26 ]
  2. Mean change in the average morning ItchRO(Obs) severity score in participants with all PFIC subtypes. [ Time Frame: Between Baseline and Week 15 through Week 26 ]
  3. Proportion of ItchRO(Obs) responders. [ Time Frame: Between Baseline and Week 15 to Week 26 ]
  4. Proportion of sBA responders. [ Time Frame: Between Baseline and Week 18 to Week 26 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed consent and assent (as applicable) per Institutional Review Board/Ethics Committee (IRB/EC)
  2. Male or female subjects with a body weight ≥5 kg, who are ≥12 months and <18 years of age at time of baseline
  3. Cholestasis as manifested by total sBA ≥3× ULN (applies to primary cohort only)
  4. An average AM ItchRO(Obs) score ≥1.5 during 4 consecutive weeks of the screening period, leading to the baseline visit (Visit 1)
  5. 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) (*valid = completed and not answered as "I don't know"; maximum allowed invalid reports = 7, no more than 2 invalid reports during the last 7 days before randomization)
  6. Diagnosis of PFIC based on the following:

    • Chronic cholestasis as manifested by persistent (>6 months) pruritus in addition to biochemical abnormalities and/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 standardofcare 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 standardofcare genotyping. ii. Subjects with PFIC phenotype without a known mutation or with another known mutation not described above or with intermittent cholestasis as manifested by fluctuating sBA levels. iii. Subjects with PFIC after internal or external biliary diversion surgery or for whom internal or external biliary diversion surgery was reversed.
  7. Male and females of non-childbearing potential. Males and non-pregnant, non-lactating females of childbearing potential who are sexually active must agree to use acceptable methods of contraception during the study and 30 days following the last dose of the study medication. Females of childbearing potential must have a negative pregnancy test
  8. Access to email or phone for scheduled remote visits
  9. Ability to read and understand the questionnaires (both caregivers and subjects above the age of assent)
  10. Access to consistent caregiver(s) during the study
  11. Subject and caregiver willingness to comply with all study visits and requirements.

Exclusion Criteria:

  1. Predicted complete absence of bile salt excretion pump (BSEP) function based on the type of ABCB11 mutation (PFIC2), as determined by a standardofcare genotyping (applies to primary cohort only). Subjects can enter the study in the Supplemental Cohort (under inclusion criteria 6.ii or 6.iii).
  2. Recurrent intrahepatic cholestasis, indicated by a history of sBA levels <3x ULN or intermittent pruritus (applies to primary cohort only)
  3. Current or recent history (<1 year) of atopic dermatitis or other non-cholestatic diseases associated with pruritus.
  4. History of surgical disruption of the enterohepatic circulation (applies to primary cohort only)
  5. 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
  6. Previous or need for imminent liver transplant
  7. Decompensated cirrhosis (international normalized ratio [INR] >1.5, albumin <30 g/L, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy)
  8. ALT or total serum bilirubin (TSB) >15× ULN at screening
  9. Presence of other liver disease
  10. 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
  11. Possibly malignant liver mass on imaging, including screening ultrasound
  12. Known diagnosis of human immunodeficiency virus (HIV) infection
  13. Any prior cancer diagnosis (except for in situ carcinoma) within 5 years of the screening visit (Visit 0)
  14. Any known history of alcohol or substance abuse
  15. Administration of bile acids or lipid binding resins, or phenylbutyrates during the screening period
  16. Criterion has been deleted as of Amendment 3
  17. Administration of any investigational drug, biologic, or medical device during the screening period
  18. Previous use of an ileal bile acid transporter inhibitor (IBATi)
  19. 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
  20. Known hypersensitivity to maralixibat or any of its excipients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03905330


Locations
Show Show 39 study locations
Sponsors and Collaborators
Mirum Pharmaceuticals, Inc.
Additional Information:
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Responsible Party: Mirum Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03905330    
Other Study ID Numbers: MRX-502
2019-001211-22 ( EudraCT Number )
First Posted: April 5, 2019    Key Record Dates
Last Update Posted: August 16, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mirum Pharmaceuticals, Inc.:
Cholestasis
Maralixibat
Mutation
PFIC
PFIC2
Bile Duct Diseases
Liver Diseases
Biliary Tract Diseases
Digestive System Diseases
Pediatric
Additional relevant MeSH terms:
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Cholestasis
Cholestasis, Intrahepatic
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases