このページは自動翻訳されたものであり、翻訳の正確性は保証されていません。を参照してください。 英語版 ソーステキスト用。

一般的な胆汁うっ滞性肝疾患に伴うそう痒症におけるマラリキシバットの評価 (EXPAND)

2026年10月1日 更新者：Mirum Pharmaceuticals, Inc.

胆汁うっ滞性そう痒症の参加者の治療におけるマラリキシバットの有効性と安全性を評価するためのランダム化二重盲検プラセボ対照第III相試験

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.

調査の概要

状態

積極的、募集していない

条件

介入・治療

詳細な説明

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

研究の種類

介入

入学 (推定)

90

段階

  • フェーズ 3

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • アメリカ
    • California
      • Los Angeles、California、アメリカ、90027
        • Children's Hospital Los Angeles (CHLA)
      • Palo Alto、California、アメリカ、94304
        • Stanford Children's Health in Palo Alto
    • Illinois
      • Chicago、Illinois、アメリカ、60611
        • Lurie Children's Hospital
    • New York
      • New York、New York、アメリカ、10016
        • NYU Langone Health
      • New York、New York、アメリカ、10032
        • Morgan Stanley Children's Hospital - NewYork Presbyterian
    • Ohio
      • Cincinnati、Ohio、アメリカ、45229
        • Cincinnati Children's Hospital Medical Center
    • Texas
      • Houston、Texas、アメリカ、77030
        • Baylor College of Medicine
    • Utah
      • Salt Lake City、Utah、アメリカ、84112
        • University of Utah
  • イギリス
      • London、イギリス
        • King's College Hospital NHS Foundation Trust
  • イタリア
      • Bergamo、イタリア、24127
        • Azienda Ospedaliera Papa Giovanni XXIII
      • Palermo、イタリア、90127
        • ISMETT - Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione
      • Rome、イタリア、00165
        • Ospedale Pediatrico Bambino Gesu
  • カナダ
    • Alberta
      • Edmonton、Alberta、カナダ、T6G 2B7
        • Stollery Children's Hospital
  • スペイン
      • Barcelona、スペイン
        • Hospital Universitario Vall d'Hebron
      • Madrid、スペイン
        • Hospital Universitario La Paz
  • ドイツ
      • Hamburg、ドイツ
        • Universitätsklinikum Hamburg Eppendorf - Klinik für Kinder- und Jugendmedizin
  • フランス
      • Marseille、フランス、13005
        • Hôpitaux Universitaires de Marseille Timone
      • Paris、フランス
        • Hôpital Kremlin Bicêtre
  • ブラジル
      • Brasília、ブラジル
        • Hospital de Criança de Brasília (HCB)
      • Porto Alegre、ブラジル
        • Hospital da Criança Santo Antonio
      • São Paulo、ブラジル
        • Hospital Sírio-Libanês
  • ポーランド
      • Warsaw、ポーランド
        • Instytut Pomnik Centrum Zdrowia Dziecka
  • レバノン
      • Beirut、レバノン
        • Hotel Dieu de France

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

6ヶ月歳以上 (子、大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：4倍

武器と介入

参加者グループ / アーム
介入・治療
実験的：Maralixibat

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

他の名前：
  • 以前は LUM001、SHP625
プラセボコンパレーター：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.
他の：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.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Mean change in the ItchRO(Obs) severity score
時間枠：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

二次結果の測定

結果測定
時間枠
総sBA（血清胆汁酸）レベルの平均変化
時間枠：ベースラインから 12 週目と 20 週目の平均まで
ベースラインから 12 週目と 20 週目の平均まで

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Mirum Pharmaceuticals, Inc.

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

便利なリンク

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2024年10月14日

一次修了 (推定)

2026年10月1日

研究の完了 (推定)

2027年2月1日

試験登録日

最初に提出

2024年8月8日

QC基準を満たした最初の提出物

2024年8月13日

最初の投稿 (実際)

2024年8月14日

学習記録の更新

投稿された最後の更新 (実際)

2026年10月6日

QC基準を満たした最後の更新が送信されました

2026年10月1日

最終確認日

2026年10月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

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

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

はい

米国FDA規制機器製品の研究

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

購読する