Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 (Maralixibat) in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis

NCT02057718 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: LUM001-5012013-003833-14
• Study Type: interventional
• Target: 33
• Locations: 4 countries
• Sites: 10

Brief Summary

This is an open label study in children with Progressive Familial Intrahepatic Cholestasis (PFIC) designed to evaluate the safety and efficacy of LUM001, also known as Maralixibat (MRX). Efficacy will be assessed by evaluating the effect of LUM001 on pruritus and the biochemical markers of pruritus associated with PFIC.

Conditions

Progressive Familial Intrahepatic Cholestasis (PFIC)

Keywords

Bile duct diseases; Intrahepatic Cholestasis; Cholestasis; PFIC; Pruritus; Cholestatic Liver Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Endpoint (Week 13) in Fasting sBA Level

  Baseline (Day 0) to Week 13

Secondary Outcomes (5)

• Change From Baseline to Week 13/ET in Pruritus as Measured by ItchRO(Obs)

  Baseline (Day 0) to Week 13

• Change From Baseline to Week 13/ET in Pruritus as Measured by ItchRO(Pt)

  Baseline (Day 0) to Week 13

• Change From Baseline to Week 13/ET in ALT

  Baseline (Day 0) to Week 13

• Change From Baseline to Week 13/ET in Total Bilirubin

  Baseline (Day 0) to Week 13

• Change From Baseline to Week 13/ET in Direct Bilirubin

  Baseline (Day 0) to Week 13

Study Arms (1)

LUM001 (Maralixibat)

EXPERIMENTAL

Participants will receive LUM001, also known as Maralixibat (MRX) twice a day (BID).

Drug: LUM001 (Maralixibat)

Interventions

LUM001 (Maralixibat) DRUG

LUM001 also known as Maralixibat (MRX) oral dose up to twice a day (BID).

LUM001 (Maralixibat)

Eligibility Criteria

• Age: 12 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. Male or female subjects between the ages of 12 months and 18 years inclusive.
• \. Diagnosis of PFIC based on:
• Intrahepatic cholestasis manifest by total serum bile acid \>3x upper limit of normal (ULN) for age and, b or c:
• Two documented mutant alleles in ATP8B1, or ABCB11.
• Evidence of chronic liver disease, excluding those listed in (see Section 16.3), with one or more of the following criteria:
• Duration of biochemical or clinical abnormalities of \>6 months, or
• Pathologic evidence of progressive liver disease, or
• Sibling of known individual affected by PFIC (predicted to be chronic).
• \. GGTP \<100 IU/L at screening. 4. Females of childbearing potential must have a negative urine or serum pregnancy test \[β human chorionic gonadotropin (β-hCG)\] during screening and a negative urine pregnancy test at the Baseline (Day 0) visit.
• \. Males and females of child-bearing potential who are sexually active, or are not currently sexually active during the study, but become sexually active during the period of the study and 30 days following the last dose of study drug, must agree and use acceptable contraception during the trial, as described in Section 8.7.1. of the protocol 6. Informed consent and assent (per IRB/EC) as appropriate. 7. Access to phone for scheduled calls from study site. 8. Caregivers and children above the age of assent must have the ability to read and understand one of the following languages: English, Spanish, US Spanish, French, German or Polish.
• \. Subjects expected to have a consistent caregiver(s) for the duration of the first 13 weeks of the study.
• \. Caregivers (and age appropriate subjects) must be willing and able to use an eDiary device as required by the study. To accommodate potential cultural restrictions within the FIC1 affected population a paper version of the ItchRO diary will be made available.
• \. Caregivers (and age appropriate subjects) using the eDiary must digitally accept the licensing agreement in the eDiary software at the outset of the study.
• \. Caregivers (and age appropriate subjects) must complete at least 10 eDiary reports (morning or evening) during each of two consecutive weeks of the screening period, prior to assignment (maximum possible reports = 14 per week). Subjects using a paper diary must complete the same number of reports within the same timeframe

You may not qualify if:

• Chronic diarrhea requiring specific intravenous fluid or nutritional intervention for the diarrhea and/or its sequelae.
• Surgical disruption of the enterohepatic circulation at the time at screening. Subjects who have undergone reversal of a prior surgical procedure intended to disrupt enterohepatic circulation and who and have a permanently restored flow of bile acids from the liver to the terminal ileum may be eligible for the study upon consultation with the Medical Monitor.
• Liver transplant.
• Decompensated cirrhosis \[international normalized ratio (INR) \> 1.5, albumin \< 30 g/L, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy\].
• ALT \>15×ULN at screening.
• History or presence of other liver disease (see Section 16.3).
• 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 (e.g., inflammatory bowel disease).
• Liver mass on imaging.
• Known diagnosis of human immunodeficiency virus (HIV) infection.
• Cancers except for in situ carcinoma, or cancers treated at least 5 years prior to screening with no evidence of recurrence.
• Any female who is pregnant or lactating or who is planning to become pregnant within 20 weeks of assignment.
• Any known history of alcohol or substance abuse.
• Administration of bile acid or lipid binding resins within 30 days prior to Baseline / Day 0 and throughout the trial.
• Administration of sodium phenylbutyrate within 30 days prior to Baseline / Day 0 and throughout the trial.
• Investigational drug, biologic, or medical device within 30 days prior to screening, or 5 half-lives of the study agent, whichever is longer.

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (10)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Hopital Femme Mere Enfant De Lyon

Bron, 69677, France

Location

The Children's Memorial Health Institute

Warsaw, 04-730, Poland

Location

Birmingham Children's Hospital

Birmingham, West Midlands, B4 6NH, United Kingdom

Location

Leeds Teaching Hospital NHS Trust

Leeds, LS1 3EX, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• Loomes KM, Squires RH, Kelly D, Rajwal S, Soufi N, Lachaux A, Jankowska I, Mack C, Setchell KDR, Karthikeyan P, Kennedy C, Dorenbaum A, Desai NK, Garner W, Jaecklin T, Vig P, Miethke A, Thompson RJ. Maralixibat for the treatment of PFIC: Long-term, IBAT inhibition in an open-label, Phase 2 study. Hepatol Commun. 2022 Sep;6(9):2379-2390. doi: 10.1002/hep4.1980. Epub 2022 May 4.

  PMID: 35507739 DERIVED

MeSH Terms

Conditions

Cholestasis, progressive familial intrahepatic 1; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Pruritus

Interventions

maralixibat

Condition Hierarchy (Ancestors)

Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Limitations of the trial such as small numbers of subjects analyzed or technical problems leading to unreliable data.

Results Point of Contact

• Title: Mirum Clinical Trials
• Organization: Mirum Pharmaceuticals

medinfo@mirumpharma.com

650-667-4085

Study Officials

• Study Director

  Mirum

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2014
• First Posted: February 7, 2014
• Study Start: March 1, 2014
• Primary Completion: May 8, 2020
• Study Completion: May 8, 2020
• Last Updated: October 23, 2023
• Results First Posted: July 12, 2021

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); US (5); GB (3); FR (1)