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NCT03905330: MARCH-PFIC

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

Completed Phase 3 Results posted Last updated 11 December 2023
What this trial tests

Phase 3 trial testing Maralixibat in Progressive Familial Intrahepatic Cholestasis (PFIC) in 93 participants. Completed in 1 September 2022.

Timeline
9 July 2019
Primary endpoint
1 September 2022
1 September 2022

Quick facts

Lead sponsorMirum Pharmaceuticals, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment93
Start date9 July 2019
Primary completion1 September 2022
Estimated completion1 September 2022
Sites31 locations across France, Colombia, Italy, Belgium, Austria, United Kingdom, Germany, Hungary

Drugs / interventions tested

Conditions studied

Sponsor

Mirum Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 1 to 17, any sex, with Progressive Familial Intrahepatic Cholestasis (PFIC). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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.

GroupValue95% CI
Primary Cohort Maralixibat-1.718-2.272 – -1.163
Primary Cohort Placebo-0.628-1.136 – -0.121
Mean Change in Total sBA Level in the Primary Cohort. Secondary · Baseline and average of Weeks 18, 22 and 26

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

GroupValue95% CI
Primary Cohort Maralixibat-175.536-256.716 – -94.356
Primary Cohort Placebo11.187-58.073 – 80.446
Mean Change in the Average Morning ItchRO(Obs) Severity Score in Participants With PFIC (PFIC1, Nt-PFIC2, PFIC3, PFIC4 and PFIC6) Secondary · Between Baseline and Week 15 through Week 26

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.

GroupValue95% CI
PFIC Cohort Maralixibat-1.811-2.178 – -1.444
PFIC Cohort Placebo-0.610-1.000 – -0.221
Mean Change in Total sBA Level in Participants With PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6) Secondary · Between Baseline and average of Weeks 18, 22 and 26

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)

GroupValue95% CI
PFIC Cohort Maralixibat-157.489-200.276 – -114.703
PFIC Cohort Placebo2.913-42.320 – 48.146
Proportion of ItchRO(Obs) Responders in the Primary Cohort Secondary · Week 15 to Week 26 using the average value from the three 4-week periods (Weeks 15-18, 19-22 and 23-26)

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.

GroupValue95% CI
Primary Cohort Maralixibat8
Primary Cohort Placebo4
Proportion of sBA Responders in the Primary Cohort Secondary · Average value from Weeks 18, 22 and 26

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.

GroupValue95% CI
Primary Cohort Maralixibat5
Primary Cohort Placebo1
Proportion of ItchRO(Obs) Responders PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6) Secondary · From Week 15 to Week 26

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.

GroupValue95% CI
PFIC Cohort Maralixibat21
PFIC Cohort Placebo8
Proportion of sBA Responders PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6) Secondary · Week 18 to Week 26

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.

GroupValue95% CI
PFIC Cohort Maralixibat15
PFIC Cohort Placebo2

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Maralixibat
Serious: 5/47 (11%)
Deaths: 0/47
Placebo
Serious: 3/46 (7%)
Deaths: 0/46

Serious adverse events (10 terms)

ReactionSystemMaralixibatPlacebo
Urinary tract infectionInfections and infestations
Accidental exposure to productInjury, poisoning and procedural complications
Blood bilirubin increasedInvestigations
CholestasisHepatobiliary disorders
CoagulopathyBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Gastroenteritis viralInfections and infestations
Idiopathic pneumonia syndromeRespiratory, thoracic and mediastinal disorders
SeizureNervous system disorders
Vitamin K deficiencyMetabolism and nutrition disorders
Other adverse events (22 terms — click to expand)

ReactionSystemMaralixibatPlacebo
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
Abdominal painGastrointestinal disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Blood bilirubin increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Alanine aminotransferase increasedInvestigations
Upper respiratory tract infectionInfections and infestations
InfluenzaInfections and infestations
VomitingGastrointestinal disorders
HyperbilirubinaemiaHepatobiliary disorders
NasopharyngitisInfections and infestations
Vitamin E decreasedInvestigations
Vitamin D decreasedInvestigations
International normalised ratio increasedInvestigations
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
Coronavirus infectionInfections and infestations
Vitamin D deficiencyMetabolism and nutrition disorders
Vitamin E deficiencyMetabolism and nutrition disorders
GastroenteritisInfections and infestations

Most-reported serious reactions: Urinary tract infection, Accidental exposure to product, Blood bilirubin increased, Cholestasis, Coagulopathy, Constipation, Gastroenteritis viral, Idiopathic pneumonia syndrome.

Data from ClinicalTrials.gov NCT03905330 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.
    Fleishman JS, Kumar S. · · 2024 · cited 267× · PMID 38664391 · DOI 10.1038/s41392-024-01811-6
  2. Membrane transporters in drug development and as determinants of precision medicine.
    Galetin A, Brouwer KLR, Tweedie D, Yoshida K, et al · · 2024 · cited 169× · PMID 38267543 · DOI 10.1038/s41573-023-00877-1
  3. Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis.
    Kamath BM, Stein P, Houwen RHJ, Verkade HJ. · · 2020 · cited 53× · PMID 32492754 · DOI 10.1111/liv.14553
  4. Pediatric Cholestatic Liver Disease: Review of Bile Acid Metabolism and Discussion of Current and Emerging Therapies.
    Kriegermeier A, Green R. · · 2020 · cited 40× · PMID 32432119 · DOI 10.3389/fmed.2020.00149
  5. Bile acid-mediated signaling in cholestatic liver diseases.
    Zeng J, Fan J, Zhou H. · · 2023 · cited 39× · PMID 37120573 · DOI 10.1186/s13578-023-01035-1
  6. Maralixibat: First Approval.
    Shirley M. · · 2022 · cited 38× · PMID 34813049 · DOI 10.1007/s40265-021-01649-0
  7. Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
    Miethke AG, Moukarzel A, Porta G, Covarrubias Esquer J, et al · · 2024 · cited 32× · PMID 38723644 · DOI 10.1016/s2468-1253(24)00080-3
  8. Recent updates on progressive familial intrahepatic cholestasis types 1, 2 and 3: Outcome and therapeutic strategies.
    Alam S, Lal BB. · · 2022 · cited 24× · PMID 35126842 · DOI 10.4254/wjh.v14.i1.98

Verify or expand the search:

Other trials of Maralixibat

Trials testing the same drug.

Other recruiting trials for Progressive Familial Intrahepatic Cholestasis (PFIC)

Currently open trials in the same condition.

Other Mirum Pharmaceuticals, Inc. trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03905330.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing