AzTrials
AzTrials

Progressive Familial Intrahepatic Cholestasis (PFIC)Phase 2INDIGONCT02057718

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

A Phase 2 study testing LUM001 (Maralixibat) in people with Progressive Familial Intrahepatic Cholestasis (PFIC), run by Mirum Pharmaceuticals, Inc. at 10 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 12 months to 18 years
What is being tested?
LUM001 (Maralixibat)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
10 sitesin 4 countries
Study dates
1 Mar 2014to 8 May 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 months to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 1. Male or female subjects between the ages of 12 months and 18 years inclusive.
  • 2. 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
Show all 14Show fewer
  • Pathologic evidence of progressive liver disease, or
  • Sibling of known individual affected by PFIC (predicted to be chronic).
  • 3. 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.
  • 5. 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.
  • 9. Subjects expected to have a consistent caregiver(s) for the duration of the first 13 weeks of the study.
  • 10. 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.
  • 11. Caregivers (and age appropriate subjects) using the eDiary must digitally accept the licensing agreement in the eDiary software at the outset of the study.
  • 12. 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

Who cannot join

  • 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).
Show all 17Show fewer
  • 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.
  • History of non-adherence to medical regimens, unreliability, mental instability or incompetence that could compromise the validity of informed consent or lead to non-adherence with the study protocol based on Investigator judgment.
  • Any other conditions or abnormalities which, in the opinion of the Investigator or Medical monitor, may compromise the safety of the subject, or interfere with the subject participating in or completing the study

Trial locations and contacts

10 sites in 4 countries.

10 sites in 4 countries

United States5 sites

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

Other trials in United States

United Kingdom3 sites

  • Birmingham Children's Hospital

    Birmingham, West Midlands, B4 6NH

  • Leeds Teaching Hospital NHS Trust

    Leeds, LS1 3EX

  • Kings College Hospital

    London, SE5 9RS

Other trials in United Kingdom

France1 site

  • Hopital Femme Mere Enfant De Lyon

    Bron, 69677

Other trials in France

Poland1 site

  • The Children's Memorial Health Institute

    Warsaw, 04-730

Other trials in Poland

About this study

Official title: Open Label Study of the Efficacy and Long Term Safety of LUM001 (Maralixibat), an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Pediatric Patients With Progressive Familial Intrahepatic Cholestasis

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.

Read the detailed description

The study is divided into 5 parts: a 4-week dose escalation period, a 4-week stable dosing period, a 5-week stable dosing period, a 59-week long-term exposure period, and an optional follow-up treatment period for eligible participants who continue treatment with LUM001. Participants in the optional follow-up treatment period will continue to receive study drug until they are eligible to enter another LUM001 study or until LUM001 is available commercially, whichever occurs first.

Being tested
LUM001 (Maralixibat)
Keywords
Bile duct diseases, Intrahepatic Cholestasis, Cholestasis, PFIC, Pruritus, Cholestatic Liver Disease
Medical subject headings
Cholestasis, progressive familial intrahepatic 1, Bile Duct Diseases, Cholestasis, Intrahepatic, Cholestasis, Pruritus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LUM001 (Maralixibat)Drug

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

Study groups in NCT02057718
Study groupRoleWhat they receive
LUM001 (Maralixibat)ExperimentalParticipants will receive LUM001, also known as Maralixibat (MRX) twice a day (BID).
Receives: Drug: LUM001 (Maralixibat)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Baseline (Day 0) to Week 13

Secondary outcomes (5)

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

    This secondary efficacy endpoint is the change from baseline to Week 13 in pruritus as measured by ItchRO(Obs) weekly average morning score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe).

    Measured: Baseline (Day 0) to Week 13

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

    This secondary efficacy endpoint is the change from baseline to Week 13 in pruritus as measured by ItchRO(Pt) weekly average morning score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe).

    Measured: Baseline (Day 0) to Week 13

  3. Change From Baseline to Week 13/ET in ALT

    Measured: Baseline (Day 0) to Week 13

  4. Change From Baseline to Week 13/ET in Total Bilirubin

    Measured: Baseline (Day 0) to Week 13

  5. Change From Baseline to Week 13/ET in Direct Bilirubin

    Measured: Baseline (Day 0) to Week 13

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Feb 2014 (estimated)
  2. Study start1 Mar 2014
  3. Primary completion8 May 2020
  4. Study completion8 May 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02057718
Sponsor's protocol ID
LUM001-501
Other IDs
2013-003833-14
Acronym
INDIGO
Status last verified
Oct 2023
First submitted
5 Feb 2014
Last updated
23 Oct 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 35507739

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LUM001 (Maralixibat) in people with Progressive Familial Intrahepatic Cholestasis (PFIC), run by Mirum Pharmaceuticals, Inc. at 10 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, United Kingdom, France, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Endpoint (Week 13) in Fasting sBA Level (time frame: Baseline (Day 0) to Week 13). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02057718, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in