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지보텐탄 및 다파글리플로진 조합, 간경변증에서 평가(ZEAL 연구) (ZEAL)

2026년 8월 31일 업데이트: AstraZeneca

간경변 환자에서 Zibotentan과 Dapagliflozin, Dapagliflozin 단일 요법과 위약의 병용 요법의 효능, 안전성 및 내약성을 평가하기 위한 2단계 IIa/b상 다기관, 무작위, 이중 맹검, 위약 대조, 병렬 그룹 용량 범위 연구 문맥 고혈압의 특징

This is a two part Phase IIa/b multicentre, randomised, double-blind, placebo-controlled, parallel group dose-ranging study to assess the efficacy, safety, and tolerability of the combination of zibotentan and dapagliflozin, and dapagliflozin monotherapy versus placebo in participants with cirrhosis with features of portal hypertension.

연구 개요

상태

종료됨

정황

개입 / 치료

상세 설명

Part A will assess the efficacy, safety, and tolerability of the combination of B mg zibotentan and 10 mg dapagliflozin versus placebo in participants with Child-Pugh A cirrhosis with features of portal hypertension and with no history of decompensation events.

If the safety profile is determined to be acceptable at the conclusion of Part A, Part B will investigate efficacy, safety, and tolerability of A mg, B mg, or C mg zibotentan combined with 10 mg dapagliflozin and of 10 mg dapagliflozin monotherapy versus placebo in participants with cirrhosis with features of portal hypertension. Part B will include a broader range of Child- Pugh A and Child-Pugh B cirrhosis participants, including those with more severe disease, a history of decompensation events, or current ascites.

The study will be conducted in approximately 30 to 45 study centres in North America, Asia, and Europe.

연구 유형

중재적

등록 (실제)

205

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 네덜란드
      • Amsterdam, 네덜란드, 1081 HV
        • Research Site
  • 대만
      • Taipei, 대만, 10002
        • Research Site
      • Taipei, 대만, 112
        • Research Site
  • 덴마크
      • Aarhus N, 덴마크, 8200
        • Research Site
      • Esbjerg, 덴마크, 6700
        • Research Site
      • Hvidovre, 덴마크, 2650
        • Research Site
      • Køge, 덴마크, 4600
        • Research Site
  • 독일
      • Dresden, 독일, 01307
        • Research Site
      • Landshut, 독일, 84034
        • Research Site
      • Mainz, 독일, 55131
        • Research Site
      • Münster, 독일, 48149
        • Research Site
      • Wiesbaden, 독일, 65189
        • Research Site
  • 루마니아
      • Cluj-Napoca, 루마니아, 400162
        • Research Site
  • 미국
    • Alabama
      • Birmingham, Alabama, 미국, 35233
        • Research Site
    • California
      • Pasadena, California, 미국, 91105
        • Research Site
      • San Francisco, California, 미국, 94115
        • Research Site
      • West Hollywood, California, 미국, 90048
        • Research Site
    • Minnesota
      • Rochester, Minnesota, 미국, 55905
        • Research Site
    • New York
      • The Bronx, New York, 미국, 10467
        • Research Site
    • South Carolina
      • Charleston, South Carolina, 미국, 29425
        • Research Site
    • Texas
      • Dallas, Texas, 미국, 75246
        • Research Site
    • Virginia
      • Charlottesville, Virginia, 미국, 22903
        • Research Site
      • Richmond, Virginia, 미국, 23249
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, 미국, 53226
        • Research Site
  • 벨기에
      • Edegem, 벨기에, 2650
        • Research Site
  • 스위스
      • Bern, 스위스, 3010
        • Research Site
      • Lucerne, 스위스, 6000
        • Research Site
      • Lugano, 스위스, 6900
        • Research Site
  • 스페인
      • Barcelona, 스페인, 08035
        • Research Site
      • Barcelona, 스페인, 08036
        • Research Site
      • Barcelona, 스페인, 08041
        • Research Site
      • Madrid, 스페인, 28034
        • Research Site
      • Madrid, 스페인, 28007
        • Research Site
      • Majadahonda, 스페인, 28222
        • Research Site
      • Santander, 스페인, 39008
        • Research Site
  • 영국
      • Birmingham, 영국, B9 5SS
        • Research Site
      • Cambridge, 영국, CB2 0XY
        • Research Site
      • London, 영국, SE5 9RS
        • Research Site
  • 오스트리아
      • Vienna, 오스트리아, 1090
        • Research Site
  • 중국
      • Beijing, 중국, 100057
        • Research Site
      • Chengdu, 중국, 610000
        • Research Site
      • Guangzhou, 중국, 510515
        • Research Site
      • Hangzhou, 중국, 310015
        • Research Site
  • 체코
      • Prague, 체코, 128 00
        • Research Site
      • Prague, 체코, 169 02
        • Research Site
  • 프랑스
      • Angers, 프랑스, 49933
        • Research Site
      • Clichy, 프랑스, 92110
        • Research Site
      • Paris, 프랑스, 75651
        • Research Site
      • Toulouse, 프랑스, 31059
        • Research Site
  • 호주
      • Heidelberg, 호주, 3084
        • Research Site

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Study principal inclusion criteria For both Part A and Part B

  1. No current or prior (within 1 month of enrolment) medical treatment with an SGLT2 inhibitor or ERAs.

  2. On no or a stable dose of beta blockers, with no major dose changes within 1 month prior to the first dose of study intervention.

  3. Provision of signed and dated, written ICF prior to any mandatory study-specific procedures, sampling, and analyses.

  4. Female participants of non-childbearing potential confirmed at screening by fulfilling one of the following criteria:

    1. Post-menopausal: defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments; and also, FSH levels in the post-menopausal range by central laboratory.
    2. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

  5. Female participants must have a negative pregnancy test at screening and must not be lactating

Part A participants who have the following:

  1. Clinical and/or histological diagnosis of cirrhosis with either (i) features of portal hypertension or (ii) liver stiffness ≥ 21 kPa.
  2. MELD score < 15.
  3. Child-Pugh score ≤ 6.
  4. No clinically evident ascites.
  5. No evidence of worsening of hepatic function (eg, no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status) within the last month prior to dosing, as determined by the investigator or usual practitioner.
  6. HVPG recording of good enough quality as judged by a central reader.

Part B participants who have the following:

  1. Clinical and/or histological diagnosis of cirrhosis and either history of decompensation or compensated cirrhosis with signs of clinically significant portal hypertension.
  2. HVPG recording of good enough quality and HVPG > 10 mmHg, as judged by a central reader.
  3. MELD score < 15.
  4. Child-Pugh score < 10.
  5. No ascites or ascites up to grade 2 without change in diuretic treatment within the last month prior to first dose and no paracentesis within the last month or planned paracentesis in the next 4 months at screening.
  6. No evidence of worsening of hepatic function (eg, no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status) within the last month prior to dosing, as determined by the investigator or usual practitioner.

Study principal exclusion criteria:

  1. Any evidence of a clinically significant disease which in the investigator's opinion makes it undesirable for the participant to participate in the study.
  2. Liver cirrhosis caused by chronic cholestatic liver disease
  3. ALT or AST ≥ 150 U/L and/or total bilirubin ≥ 3 × ULN
  4. Acute liver injury caused by drug toxicity or by an infection.
  5. Any history of hepatocellular carcinoma.
  6. Liver transplant or expected liver transplantation within 6 months of screening.
  7. History of TIPS or a planned TIPS within 6 months from enrolment into the study.
  8. Active treatment for HCV within the last 1 year or HBV antiviral therapy for less than 1 year.
  9. Participants with T1DM.

Medical Conditions (Part A only)

  1. INR > 1.5.
  2. Serum/plasma levels of albumin ≤ 35 g/L.
  3. Platelet count < 75 × 109/L.
  4. History of ascites
  5. History of hepatic hydrothorax
  6. History of portopulmonary syndrome
  7. History of hepatic encephalopathy
  8. History of variceal haemorrhage
  9. History of acute kidney injury
  10. History of heart failure, including high output heart failure (eg, due to hyperthyroidism or Paget's disease)

Medical Conditions (Part B only)

  1. INR > 1.7.
  2. Serum/plasma levels of albumin ≤ 28 g/L.
  3. Platelet count < 50 × /109L.
  4. Acute kidney injury within 3 months of screening.
  5. History of encephalopathy of West Haven grade 2 or higher within 6 months prior to screening.
  6. History of variceal haemorrhage within 6 months prior to screening.
  7. NYHA functional heart failure class III or IV or with unstable heart failure requiring hospitalisation for optimisation of heart failure treatment and who are not yet stable on heart failure therapy within 6 months prior to screening.
  8. Heart failure due to cardiomyopathies that would primarily require specific other treatment: eg, cardiomyopathy due to pericardial disease, amyloidosis or other infiltrative diseases, cardiomyopathy related to congenital heart disease, primary hypertrophic cardiomyopathy, cardiomyopathy related to toxic or infective conditions (ie, chemotherapy, infective myocarditis, septic cardiomyopathy).
  9. High output heart failure (eg, due to hyperthyroidism or Paget's disease).
  10. Heart failure due to primary cardiac valvular disease/dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 상영
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 삼루타

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Part A: Treatment Group 1

Participants will receive once daily dose of placebo matching zibotentan capsule + placebo matching dapagliflozin tablet for 6 weeks.
의약품: Part A: Placebo (matching zibotentan capsule & matching dapagliflozin tablet)

placebo capsule (matching zibotentan capsule)

placebo tablet (matching dapagliflozin tablet)
실험적: Part A: Treatment Group 2

Participants will receive once daily dose of zibotentan capsule + dapagliflozin tablet for 6 weeks.
의약품: Part A: zibotentan (dose B) + dapagliflozin

zibotentan capsule

dapagliflozin tablet
실험적: Part B: Treatment Group 1

Participants will receive once daily dose of placebo matching zibotentan capsule + placebo matching dapagliflozin tablet for 16 weeks.
의약품: Part B: Placebo (matching zibotentan capsule & matching dapagliflozin tablet)

placebo capsule (matching zibotentan capsule)

placebo tablet (matching dapagliflozin tablet)
실험적: Part B: Treatment Group 2

Participants will receive once daily dose of placebo matching zibotentan capsule + dapagliflozin tablet for 16 weeks.
의약품: Part B: placebo (matching zibotentan capsule) + dapagliflozin

placebo capsule (matching zibotentan capsule)

dapagliflozin tablet
실험적: Part B: Treatment Group 3

Participants will receive once daily dose of zibotentan capsule + dapagliflozin tablet for 16 weeks.
의약품: Part B: zibotentan (dose A) + dapagliflozin

zibotentan capsule

dapagliflozin tablet
실험적: Part B: Treatment Group 4

Participants will receive once daily dose of zibotentan capsule + dapagliflozin tablet for 16 weeks.
의약품: Part B: zibotentan (dose B) + dapagliflozin

zibotentan capsule

dapagliflozin tablet
실험적: Part B: Treatment Group 5

Participants will receive once daily dose of zibotentan capsule + dapagliflozin tablet for 16 weeks.
의약품: Part B: zibotentan (dose C) + dapagliflozin

zibotentan capsule

dapagliflozin tablet

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Absolute Change in HVPG From Baseline to Week 6, Part A
기간: From Baseline to Week 6

Absolute change in Hepatic venous pressure gradient from baseline to week 6.
From Baseline to Week 6
Absolute Change in HVPG From Baseline to Week 6, Part B
기간: From Baseline to Week 6

Absolute change in Hepatic venous pressure gradient from baseline to week 6.
From Baseline to Week 6

2차 결과 측정

결과 측정
측정값 설명
기간
HVPG Percentage Change From Baseline to Week 6, Part A
기간: From Baseline to Week 6

Hepatic venous pressure gradient percentage change from baseline to week 6, Part A.
From Baseline to Week 6
HVPG Percentage Change From Baseline to Week 6, Part B
기간: From baseline to week 6

Hepatic venous pressure gradient percentage change from baseline to week 6, Part B.
From baseline to week 6
Number of Participants With HVPG Response at Week 6, Part A
기간: From baseline to week 6

A HVPG responder is defined as a subject having <10 mmHg at week 6 if baseline HVPG >=10 or a reduction of >=1.5 mmHg from baseline to week 6. n: Number of subjects in analysis. N: Number of subjects per treatment group.
From baseline to week 6
Number of Participants With HVPG Response at Week 6, Part B
기간: From baseline to Week 6

A HVPG responder in Part B is defined as a subject having at least 20% decrease or a reduction to or below 12 mmHg if baseline HVPG > 12 mmHG from baseline to Week 6.
From baseline to Week 6
Change in Body Weight (kg) Over Time Course of Study, Part A
기간: From baseline to Week 6

The analysis is performed using MMRM. The model includes the continuous covariate of the Baseline measurements as the fixed effect covariate and fixed categorical effects of treatment group, visit, and treatmentby-visit interaction.
From baseline to Week 6
Change in Body Weight (kg) Over Time Course of Study, Part B
기간: From baseline to Week 6 and Week 16

The analysis is performed using MMRM. The model includes the continuous covariate of the Baseline measurements as the fixed effect covariate and fixed categorical effects of treatment group, visit, and treatmentby-visit interaction.
From baseline to Week 6 and Week 16
Change in Total Dosage of Loop-diuretic Equivalents Use From Baseline to Week 6, Part A
기간: From baseline to Week 6

Change in total dosage of loop-diuretic equivalents use from baseline to Week 6, Part A. A loop-diuretic equivalent is based on 40 mg furosemide = 1 mg bumetanide = 20 mg torsemide = 50 mg ethacrynic acid.
From baseline to Week 6
Change in Total Dosage of Loop-diuretic Equivalents Use From Baseline to Week 6 and Week 16, Part B
기간: From Baseline to Week 6 and Week 16

Change in total dosage of loop-diuretic equivalents use from baseline to Week 6, Part B. A loop-diuretic equivalent is based on 40 mg furosemide = 1 mg bumetanide = 20 mg torsemide = 50 mg ethacrynic acid.
From Baseline to Week 6 and Week 16
Change in Total Body Water From Baseline to Week 6, Part A
기간: From Baseline to Week 6

Change in total body water from baseline to Week 6, Part A. The analysis is performed using MMRM.
From Baseline to Week 6
Change in Total Body Water From Baseline to Week 6 and Week 16, Part B
기간: From Baseline to Week 6 and Week 16

Change in total body water from baseline to Week 6 and Week 16, Part B. The analysis is performed using MMRM.
From Baseline to Week 6 and Week 16
Change in Extracellular Water From Baseline to Week 6, Part A
기간: From baseline to Week 6

Change in extracellular water from baseline to Week 6, Part A. The analysis is performed using MMRM. Bioimpedance spectroscopy (BIS) was performed at the study centre to monitor body water volumes and body fat mass.
From baseline to Week 6
Change in Extracellular Water From Baseline to Week 6 and Week 16, Part B
기간: From Baseline to Week 6 and to Week 16

Change in extracellular water from baseline to Week 6 and Week 16, Part B. The analysis is performed using MMRM. Bioimpedance spectroscopy (BIS) was performed at the study centre to monitor body water volumes and body fat mass.
From Baseline to Week 6 and to Week 16
Change in Intracellular Water From Baseline to Week 6, Part A
기간: From Baseline to Week 6

Change in intracellular water from Baseline to Week 6, Part A. The analysis is performed using MMRM. Bioimpedance spectroscopy (BIS) was performed at the study centre to monitor body water volumes and body fat mass.
From Baseline to Week 6
Change in Intracellular Water From Baseline to Week 6 and Week 16, Part B
기간: From Baseline to Week 6 and Week 16

Change in intracellular water from Baseline to Week 6 and Week 16, Part B. The analysis is performed using MMRM. Bioimpedance spectroscopy (BIS) was performed at the study centre to monitor body water volumes and body fat mass.
From Baseline to Week 6 and Week 16
Change in Total Body Fat Mass From Baseline to Week 6, Part A
기간: From baseline to Week 6

Change in total body fat mass from Baseline to Week 6, Part A. The analysis is performed using MMRM. Bioimpedance spectroscopy (BIS) was performed at the study centre to monitor body water volumes and body fat mass.
From baseline to Week 6
Change in Total Body Fat Mass From Baseline to Week 6 and Week 16, Part B
기간: From Baseline to Week 6 and Week 16

Change in total body fat mass from Baseline to Week 6 and Week 16, Part B. The analysis is performed using MMRM. Bioimpedance spectroscopy (BIS) was performed at the study centre to monitor body water volumes and body fat mass.
From Baseline to Week 6 and Week 16
Change in Systolic Blood Pressure From Baseline to Week 6, Part A
기간: From Baseline to Week 6

Change in systolic blood pressure from baseline to Week 6, Part A. The analysis is performed using MMRM.
From Baseline to Week 6
Change in Systolic Blood Pressure From Baseline to Week 6 and Week 16, Part B
기간: From baseline to Week 6 and Week 16

Change in systolic blood pressure from baseline to Week 6 and Week 16, Part B. The analysis is performed using MMRM.
From baseline to Week 6 and Week 16
Change in Diastolic Blood Pressure From Baseline to Week 6, Part A
기간: From Baseline to Week 6

Change in diastolic blood pressure from baseline to Week 6, Part A. The analysis is performed using MMRM.
From Baseline to Week 6
Change in Diastolic Blood Pressure From Baseline to Week 6 and Week 16, Part B
기간: From baseline to Week 6 and Week 16

Change in diastolic blood pressure from baseline to Week 6 and Week 16, Part B. The analysis is performed using MMRM.
From baseline to Week 6 and Week 16

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

AstraZeneca

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

유용한 링크

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2022년 10월 31일

기본 완료 (실제)

2025년 5월 22일

연구 완료 (실제)

2025년 7월 17일

연구 등록 날짜

최초 제출

2022년 8월 24일

QC 기준을 충족하는 최초 제출

2022년 8월 24일

처음 게시됨 (실제)

2022년 8월 25일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 25일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 8월 31일

마지막으로 확인됨

2026년 8월 1일

추가 정보

이 연구와 관련된 용어

추가 관련 MeSH 약관

기타 연구 ID 번호

  • D4326C00003
  • 2021-006577-30 (EudraCT 번호)

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD 공유 기간

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD 공유 액세스 기준

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD 공유 지원 정보 유형

  • 연구_프로토콜
  • 수액

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다