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Évaluation du Maralixibat dans le prurit associé à une maladie hépatique cholestatique générale (EXPAND)

1 octobre 2026 mis à jour par: Mirum Pharmaceuticals, Inc.

Étude de phase 3 randomisée en double aveugle contrôlée par placebo pour évaluer l'efficacité et l'innocuité du maralixibat dans le traitement des participants atteints de prurit cholestatique

The purpose of this study is to determine whether the investigational treatment (maralixibat) is safe and effective in pediatric and adult participants who have cholestatic liver disease with pruritus that has been refractory to other therapies, and who have no other treatment options.

Aperçu de l'étude

Statut

Actif, ne recrute pas

Les conditions

Intervention / Traitement

Description détaillée

This study will be conducted in multiple sites in North America, Europe, Middle East and South America.

Type d'étude

Interventionnel

Inscription (Estimé)

90

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Allemagne
      • Hamburg, Allemagne
        • Universitätsklinikum Hamburg Eppendorf - Klinik für Kinder- und Jugendmedizin
  • Brésil
      • Brasília, Brésil
        • Hospital de Criança de Brasília (HCB)
      • Porto Alegre, Brésil
        • Hospital da Criança Santo Antonio
      • São Paulo, Brésil
        • Hospital Sírio-Libanês
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
        • Stollery Children's Hospital
  • Espagne
      • Barcelona, Espagne
        • Hospital Universitario Vall d'Hebron
      • Madrid, Espagne
        • Hospital Universitario La Paz
  • France
      • Marseille, France, 13005
        • Hôpitaux Universitaires de Marseille Timone
      • Paris, France
        • Hôpital Kremlin Bicêtre
  • Italie
      • Bergamo, Italie, 24127
        • Azienda Ospedaliera Papa Giovanni XXIII
      • Palermo, Italie, 90127
        • ISMETT - Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione
      • Rome, Italie, 00165
        • Ospedale Pediatrico Bambino Gesu
  • Liban
      • Beirut, Liban
        • Hotel Dieu de France
  • Pologne
      • Warsaw, Pologne
        • Instytut Pomnik Centrum Zdrowia Dziecka
  • Royaume-Uni
      • London, Royaume-Uni
        • King's College Hospital NHS Foundation Trust
  • États-Unis
    • California
      • Los Angeles, California, États-Unis, 90027
        • Children's Hospital Los Angeles (CHLA)
      • Palo Alto, California, États-Unis, 94304
        • Stanford Children's Health in Palo Alto
    • Illinois
      • Chicago, Illinois, États-Unis, 60611
        • Lurie Children's Hospital
    • New York
      • New York, New York, États-Unis, 10016
        • NYU Langone Health
      • New York, New York, États-Unis, 10032
        • Morgan Stanley Children's Hospital - NewYork Presbyterian
    • Ohio
      • Cincinnati, Ohio, États-Unis, 45229
        • Cincinnati Children's Hospital Medical Center
    • Texas
      • Houston, Texas, États-Unis, 77030
        • Baylor College of Medicine
    • Utah
      • Salt Lake City, Utah, États-Unis, 84112
        • University of Utah

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

6 mois et plus (Enfant, Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  1. Informed consent and assent (as applicable)

  2. Age ≥6 months at time of baseline visit

  3. Diagnosis of a rare cholestatic liver disease with cholestatic pruritus based on the following:

    1. Chronic liver biochemical abnormalities (>90 days) and/or pathological evidence of progressive liver disease. Total sBA >2× ULN is required.
    2. Persistent pruritus (>90 days). An average worst-daily (morning and evening) ItchRO(Obs)/ItchRO(Pt) score ≥1.5 during the 2 consecutive weeks of the screening period leading to the baseline visit. If both instruments are administered, a score ≥1.5 is required only for ItchRO(Obs).

    Participants with the following rare diseases will be enrolled in the study:

    Any rare cholestatic liver disease associated with persistent cholestatic pruritus, including but not limited to the following: alpha-1 antitrypsin deficiency, ARC syndrome, BA, Caroli's disease, ciliopathies, hepatic sarcoidosis, idiopathic amyloidosis, IgG4-related sclerosing cholangitis, ischemic cholangiopathy, metabolic or genetic cholestatic liver diseases (e.g., bile acid synthesis defects, defects of bile acid transport or disorders such as transaldolase deficiency, where chronic cholestasis and pruritus are present), secondary sclerosing cholangitis.

  4. Completion of at least 10 valid daily (morning and evening) ItchRO(Obs)/ItchRO(Pt) entries during 2 consecutive weeks of the screening period, leading to the baseline visit. Each week should have at least 4 valid daily (morning and evening) entries. If both instruments are administered, the completion criterion is required only for ItchRO(Obs).

  5. If taking antipruritics or ursodeoxycholic acid, the participant has to be on a stable dosing regimen (i.e., same dose and frequency in the 30 days prior to the screening visit and will continue this dosing regimen up to Week 40 [adjustment for body weight is allowed]).

  6. Non-pregnant, non-lactating females of childbearing potential who are sexually active must agree to use at least an acceptable effective method of contraception during the study. Females of childbearing potential must have a negative pregnancy test result.

  7. Access to email or telephone for scheduled participant contacts and access to smart phone or tablet for PROs (Exception: Participants who do not use a smart phone or tablet because of cultural restrictions will complete the PROs on paper.)

  8. Ability to read and/or understand the questionnaires (both caregivers and participants ≥9 years of age)

  9. For participants ≤18 years of age: Access to consistent caregiver(s) during the study

  10. Willingness (participant or caregiver) to comply with all study visits and requirements through the end of the study

Exclusion Criteria:

Those who meet any of the following criteria are NOT eligible to participate in the study:

Patient Characteristics

  1. Diagnosis of ALGS, ICP, PBC, PFIC, or PSC

  2. Active atopic dermatitis or other non-cholestatic diseases associated with pruritus that are not controlled by standard treatment and that may interfere with the severity assessment of cholestasis-associated pruritus

  3. Decompensated cirrhosis or complications of cirrhosis (e.g., esophageal or gastric variceal bleeding in the last 6 months, high-risk esophageal or gastric varices [e.g., large, coiled, occupying >1/3 of the esophageal lumen, red varices or red signs], ascites, hepatic encephalopathy, hepatorenal syndrome). Patients with compensated cirrhosis with preserved hepatic synthetic function (see Exclusion Criterion #6) and absence of complications are eligible.

  4. Suspected or proven cholangiocarcinoma or hepatocellular carcinoma

  5. Unstable and/or serious medical disease that is likely to impair the ability to participate in all aspects of the study, confound efficacy and/or safety assessments, or result in substantially shortened life expectancy (e.g., any active malignancy including hematological malignancy, end-stage heart failure, active infection, acute and chronic diarrhea). Exceptionally, previous history of malignancy, adequately treated/in remission, that in opinion of investigator and medical monitor does not impact participant safety and participation in the study, may be allowed. The investigator should contact the medical monitor to discuss these cases and seek approval before the screening period.

  6. Laboratory results during the screening visit as follows:

    1. Platelet count <70,000/mm3

      . Patients with any condition that further increases bleeding risk (e.g., recent clinically relevant bleeding event [6 months], recent major surgery [12 weeks], anticoagulant use, platelet function disorders) are excluded.

    2. Albumin <30 g/L

    3. INR ≥1.5 (after intravenous or subcutaneous supplementation of vitamin K)

    4. Total bilirubin: For participants <18 years of age: total bilirubin >10 mg/dL For participants ≥18 years of age: total bilirubin ≥3× ULN

    5. ALT: For participants <18 years of age: ALT >10× ULN For participants ≥18 years of age: ALT >5× ULN

  7. 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., clinically relevant inflammatory bowel disease involving the terminal ileum), per investigator discretion

  8. History of liver transplant Prior/Concomitant Therapy

  9. Use of an IBAT inhibitor within 8 weeks prior to the screening visit

  10. Use of any other investigational medication within 30 days or 5 times the half-life, whichever is greater, prior to the screening visit Other Exclusions

  11. Pregnant or nursing

  12. Known intolerance/hypersensitivity to maralixibat or its excipients

  13. History of nonadherence to medical regimens, unreliability, medical condition, mental instability, or cognitive impairment that, in the opinion of the investigator, could compromise the validity of informed consent, compromise the safety of the participant, or lead to nonadherence with the study protocol or inability to conduct the study procedures

  14. Clinically relevant alcohol use disorder or drug abuse within 12 weeks of screening:

    1. Moderate alcohol consumption as defined for this study by >1 and >2 standard drinks on average per day for women and men, respectively, within 12 weeks prior to the screening visit. A standard drink is defined as 44 mL (1.5 oz, one shot) of liquor, 148 mL (5 oz) of nonfortified wine, or 355 mL (12 oz) of beer (1 oz=29.57 mL; NIAAA)
    2. Drug abuse within the 12 weeks prior to, or a positive drug screening result at, the screening visit unless it can be explained by a drug prescription. A positive drug screen will exclude participants if the investigator deems the result to be reflective of a pattern of behavior that might impair the participant's ability to participate in the study.
    3. Use of cannabinoids (legal, prescribed, or otherwise) is allowed, provided use is stable (including as-needed use without need for increased frequency of use) for ≥12 weeks prior to the screening visit and throughout the entire study duration.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Maralixibat

Participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 39 weeks.
Médicament: Maralixibat

Maralixibat will be provided as an oral solution along with 0.5-, 1.0-, and 3.0-mL sized dosing dispensers. During the double-blind dose escalation period (4 weeks), the study drug (maralixibat) will be administered once daily for 1 week and then twice daily (BID; morning and evening). During the double-blind stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the double-blind dose-escalation period) of maralixibat. During the open-label dose escalation period (4 weeks), all participants will receive maralixibat treatment once daily for 1 week and then twice daily (BID; morning and evening). During the open-label stable dosing period (at least 16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the open-label dose-escalation period) of maralixibat.

Autres noms:
  • Anciennement LUM001, SHP625
Comparateur placebo: Placebo

Participants will receive placebo matched to maralixibat oral solution orally once daily for 1 week and then twice daily for 19 weeks. After 20 weeks, participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 19 weeks.
Autre: Placebo

Placebo matched to maralixibat will be provided as an oral solution along with 0.5-, 1.0-, and 3.0-mL sized dosing dispensers. During the double-blind dose escalation period (4 weeks), study drug will be administered once daily for 1 week and then twice daily (BID; morning and evening). During the double-blind stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the double-blind dose-escalation period) of study drug. During the open-label dose escalation period (4 weeks), all participants will receive maralixibat treatment once daily for 1 week and then twice daily (BID; morning and evening). During the open-label stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the open-label dose-escalation period) of maralixibat.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Mean change in the ItchRO(Obs) severity score
Délai: From baseline to average of week 13 to week 20

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.
From baseline to average of week 13 to week 20

Mesures de résultats secondaires

Mesure des résultats
Délai
Changement moyen du niveau total de sBA (acide biliaire sérique)
Délai: De la ligne de base à la moyenne de la semaine 12 et de la semaine 20
De la ligne de base à la moyenne de la semaine 12 et de la semaine 20

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Mirum Pharmaceuticals, Inc.

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

14 octobre 2024

Achèvement primaire (Estimé)

1 octobre 2026

Achèvement de l'étude (Estimé)

1 février 2027

Dates d'inscription aux études

Première soumission

8 août 2024

Première soumission répondant aux critères de contrôle qualité

13 août 2024

Première publication (Réel)

14 août 2024

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

6 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

1 octobre 2026

Dernière vérification

1 octobre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • MRX-802
  • 2024-511287-85-00 (Ctis)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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