AzTrials
AzTrials

Progressive Familial Intrahepatic Cholestasis (PFIC)Phase 3MARCH-PFICNCT03905330

A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC)

A Phase 3 study testing Maralixibat in people with Progressive Familial Intrahepatic Cholestasis (PFIC), run by Mirum Pharmaceuticals, Inc. at 31 sites in 17 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

The purpose of this study is to determine whether the investigational treatment (maralixibat) is safe and effective in pediatric participants with Progressive Familial Intrahepatic Cholestasis (PFIC). Read more about this study

Who is it for?
Ages 1 year to 17 years
What is being tested?
Maralixibat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
93 participants
Where
31 sitesin 17 countries
Study dates
9 Jul 2019to 1 Sep 2022
Phase
Phase 3
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 1 year to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Informed consent and assent (as applicable) per Institutional Review Board/Ethics Committee (IRB/EC)
  • Male or female subjects with a body weight ≥5 kg, who are ≥12 months and <18 years of age at time of baseline
  • Cholestasis as manifested by total sBA ≥3× ULN (applies to primary cohort only)
  • 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) (*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)
  • Diagnosis of PFIC based on the following:
Show all 14Show fewer
  • 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 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 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.
  • 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
  • Access to email or phone for scheduled remote visits
  • Ability to read and understand the questionnaires (both caregivers and subjects above the age of assent)
  • Access to consistent caregiver(s) during the study
  • Subject and caregiver willingness to comply with all study visits and requirements.

Who cannot join

  • 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 (applies to primary cohort only)
  • 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
Show all 20Show fewer
  • 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 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 phenylbutyrates during the screening period
  • Criterion has been deleted as of Amendment 3
  • 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
  • Known hypersensitivity to maralixibat or any of its excipients.

Trial locations and contacts

31 sites in 17 countries.

31 sites in 17 countries

United States11 sites
  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Cincinnati Children's Hospital

    Cincinnati, Ohio, 45229

  • Cleveland Clinic - Pediatric Institute

    Cleveland, Ohio, 44195

  • University of Texas - UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Children's Hospital Los Angeles CHLA

    Los Angeles, California, 90027

  • The Children's Hospital at Montefiore Yeshiva University - Montefiore Medical Center

    New York, New York, 10461

  • Advent Health

    Orlando, Florida, 32803

  • UPMC Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15224

  • University of Texas, Health Science Center San Antonio

    San Antonio, Texas, 78229

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Medstar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007-2113

Other trials in United States

France3 sites
  • Hospices Civils de Lyon - Hopital Femme Mere Enfant Service de Gastroenterologie, Hepatologie et Nutrition

    Lyon

  • CHU de Marseille, Hôpital de la Timone

    Marseille

  • CHU de Toulouse - Hôpital des Enfants

    Toulouse, 31059

Other trials in France

Italy2 sites
  • Hospital Papa Giovanni XXIII / Unità di Pediatria

    Bergamo

  • Ospedale Pediatrico Bambino Gesu

    Roma

Other trials in Italy

United Kingdom2 sites
  • Birmingham Children's Hospital

    Birmingham

  • King's College Hospital NHS

    London

Other trials in United Kingdom

Argentina1 site
  • Hospital Italiano de Buenos Aires

    Buenos Aires

Other trials in Argentina

Austria1 site
  • Medizinische Universität Wien, Universitätsklinik für Kinder- und Jugendheilkunde

    Vienna

Other trials in Austria

Belgium1 site
  • Universite Catholique de Louvain (UCLouvain) - Cliniques Universitaires Saint-Luc

    Brussels

Other trials in Belgium

Brazil1 site
  • Sociedade Beneficente de Senhoras Hospital Sírio-Libanês

    São Paulo

Other trials in Brazil

Canada1 site
  • University of Alberta - Women and Children's Health Research Institute

    Edmonton

Other trials in Canada

Colombia1 site
  • Fundacion Cardioinfantil - Departamento de Investigaciones

    Bogotá

Other trials in Colombia

Germany1 site
  • Medizinische Hochschule Hannover

    Hanover

Other trials in Germany

Hungary1 site
  • Semmelweis Egyetem - Altalanos Orvostudomanyi Kar (SE AOK)

    Budapest, 1083

Other trials in Hungary

Lebanon1 site
  • Hotel Dieu de France

    Beirut

Other trials in Lebanon

Mexico1 site
  • Consultario de Joshue David Covarrubias Esquer

    Zapopan

Other trials in Mexico

Poland1 site
  • Instytut Pomnik Centrum Zdrowia Dziecka

    Warsaw

Other trials in Poland

Singapore1 site
  • KK Women's and Children's Hospital

    Singapore

Other trials in Singapore

Turkey (Türkiye)1 site
  • Koc University Hospital

    Istanbul

Other trials in Turkey (Türkiye)

About this study

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

The purpose of this study is to determine whether the investigational treatment (maralixibat) is safe and effective in pediatric participants with Progressive Familial Intrahepatic Cholestasis (PFIC).

Read the detailed description

This study was conducted at multiple sites in North America, Europe, Asia and South America.

Being tested
Maralixibat, Placebo
Keywords
Cholestasis, Maralixibat, Mutation, PFIC, PFIC2, Bile Duct Diseases, Liver Diseases, Biliary Tract Diseases, Digestive System Diseases, Pediatric
Medical subject headings
Cholestasis, progressive familial intrahepatic 1, Cholestasis, Bile Duct Diseases, Liver Diseases, Biliary Tract Diseases, Digestive System Diseases

What participants receive

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

  • MaralixibatDrug

    Also called Formerly LUM001 and SHP625

    Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.

  • PlaceboOther

    Placebo matching to maralixibat orally twice daily for 26 weeks.

Study groups in NCT03905330
Study groupRoleWhat they receive
MaralixibatExperimentalParticipants will receive Maralixibat oral solution (up to 600 microgram per kilogram [mcg/kg]) orally twice daily for 26 weeks.
Receives: Drug: Maralixibat
PlaceboPlacebo comparatorParticipants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
Receives: Other: Placebo

What is being measured

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

  1. Mean Change in the Average Morning ItchRO(Obs) Severity Score in the Primary Cohort

    The primary efficacy endpoint is the mean change in the average morning ItchRO(Obs) severity score between baseline and Weeks 15-26, using 4-week average morning ItchRO(Obs) severity scores (Mixed Model Repeated Measures). The baseline average morning ItchRO(Obs) severity score is defined as the 4-week average morning ItchRO(Obs) severity score prior to the first dose of the study medication.

    ItchRo(Obs) Severity Score = Itch Reported Outcome Observer assessment severity score; scale between 0 (not itchy at all) and 4 (extremely itchy); the lower the score the better.

    Measured: MMRM model was used with inputs of the average changes from baseline (BL) to Weeks 1-6, 7-10, 11-14, 15-18, 19-22, 23-26, and other covariates. The average change from BL over Weeks 15-26 is calculated in the model and presented as a single number.

Secondary outcomes (7)
  1. Mean Change in Total sBA Level in the Primary Cohort.

    Mean change in total sBA level between baseline and average of Weeks 18, 22 and 26.

    Measured: Baseline and average of Weeks 18, 22 and 26

  2. Mean Change in the Average Morning ItchRO(Obs) Severity Score in Participants With PFIC (PFIC1, Nt-PFIC2, PFIC3, PFIC4 and PFIC6)

    Mean change in the average morning ItchRO(Obs) severity score between baseline and Week 15 through Week 26 in participants with PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6).

    ItchRo(Obs) Severity Score = Itch Reported Outcome Observer assessment severity score; scale between 0 (not itchy at all) and 4 (extremely itchy); the lower the score the better.

    Measured: Between Baseline and Week 15 through Week 26

  3. Mean Change in Total sBA Level in Participants With PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6)

    Mean change in total sBA level between baseline and average of Weeks 18, 22, and 26 in participants with PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6)

    Measured: Between Baseline and average of Weeks 18, 22 and 26

  4. Proportion of ItchRO(Obs) Responders in the Primary Cohort

    Proportion of ItchRO(Obs) responders from Week 15 to Week 26 in participants with PFIC2 using the average value from the three 4-week periods (Weeks 15-18, 19-22 and 23-26). The number in the Subject Analysis Set refers to the number of responders.

    ItchRO responders are defined as a subject having a 4-week average morning ItchRO(Obs) severity change from baseline of ≤-1.0 or an average severity score of ≤1.0.

    Measured: Week 15 to Week 26 using the average value from the three 4-week periods (Weeks 15-18, 19-22 and 23-26)

  5. Proportion of sBA Responders in the Primary Cohort

    Proportion of sBA responders from Week 18 to Week 26 in participants with PFIC2, using the average value from Weeks 18, 22 and 26 values. The number in the Subject Analysis Set refers to the number of responders.

    sBA responders are defined as a subject having an average sBA level of <102 umol/L (applies only if baseline sBA level was ≥102 umol/L), OR a ≤-75% average percent change from baseline.

    Measured: Average value from Weeks 18, 22 and 26

  6. Proportion of ItchRO(Obs) Responders PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6)

    Proportion of ItchRO(Obs) responders from Week 15 to Week 26 in participants with PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6). The number in the Subject Analysis Set refers to the number of responders.

    ItchRO responders are defined as a subject having a 4-week average morning ItchRO(Obs) severity change from baseline of ≤-1.0 OR an average severity score of ≤1.0.

    Measured: From Week 15 to Week 26

  7. Proportion of sBA Responders PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6)

    Proportion of sBA responders from Week 18 to Week 26 in participants with PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6). The number in the Subject Analysis Set refers to the number of responders.

    sBA responders are defined as a subject having an average sBA level of <102 umol/L (applies only if baseline sBA level was ≥102 umol/L), or a ≤-75% average percent change from baseline.

    Measured: Week 18 to Week 26

Timeline

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

  1. First posted5 Apr 2019
  2. Study start9 Jul 2019
  3. Primary completion1 Sep 2022
  4. Study completion1 Sep 2022

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03905330
Sponsor's protocol ID
MRX-502
Other IDs
2019-001211-22, 2019
Acronym
MARCH-PFIC
Status last verified
Dec 2023
First submitted
1 Apr 2019
Last updated
11 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Miethke AG, Moukarzel A, Porta G, Covarrubias Esquer J, Czubkowski P, Ordonez F, Mosca A, Aqul AA, Squires RH, Sokal E, D'Agostino D, Baumann U, D'Antiga L, Kasi N, Laborde N, Arikan C, Lin CH, Gilmour S, Mittal N, Chiou FK, Horslen SP, Huber WD, Jaecklin T, Nunes T, Lascau A, Longpre L, Mogul DB, Garner W, Vig P, Hupertz VF, Gonzalez-Peralta RP, Ekong U, Hartley J, Laverdure N, Ovchinsky N, Thompson RJ. Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2024 Jul;9(7):620-631. doi: 10.1016/S2468-1253(24)00080-3. Epub 2024 May 6.

    PubMed 38723644

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Maralixibat in people with Progressive Familial Intrahepatic Cholestasis (PFIC), run by Mirum Pharmaceuticals, Inc. at 31 sites in 17 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 20 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 11 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, France, Italy, United Kingdom, Argentina and 12 more countries. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 11 Dec 2023). 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?

Mean Change in the Average Morning ItchRO(Obs) Severity Score in the Primary Cohort (time frame: MMRM model was used with inputs of the average changes from baseline (BL) to Weeks 1-6, 7-10, 11-14, 15-18, 19-22, 23-26, and other covariates. The average change from BL over Weeks 15-26 is calculated in the model and presented as a single number.). 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 NCT03905330, 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 11 Dec 2023.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in