A Pivotal Clinical Study to Investigate Efimosfermin Alfa in Participants With Biopsy-confirmed F2- or F3-stage MASH

Официальное название

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study to Investigate the Safety and Efficacy of Efimosfermin Alfa in Participants With Biopsy-Confirmed F2- or F3-Stage Metabolic Dysfunction-Associated Steatohepatitis (MASH) (ZENITH-1)

Обзор

The purpose of this study is to assess the safety and efficacy of efimosfermin alfa in the resolution of steatohepatitis and improvement of liver-related clinical outcome compared to placebo in individuals with MASH and biopsy-confirmed F2- or F3-stage fibrosis.

Вмешательства

• Препарат Efimosfermin alfa
  Efimosfermin alfa will be administered
• Препарат Efimosfermin alfa
  Efimosfermin alfa will be administered
• Препарат Placebo
  Placebo will be administered

Первичные конечные точки

• Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of steatohepatitis at Week 52 [Срок оценки: At Week 52]
• Proportion of participants experiencing resolution of steatohepatitis reading and no worsening of MASH CRN fibrosis score at Week 52 [Срок оценки: At Week 52]
• Time from randomization to an adjudicated composite liver-related clinical outcome [Срок оценки: From Randomization (Day 1) to 48 months]

Вторичные конечные точки (12)

• Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity [Срок оценки: At Week 52 and at Month 48]
• Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity [Срок оценки: At Week 52 and at Month 48]
• Number of participants with Grade 3 and Grade 4 laboratory abnormalities [Срок оценки: At Week 52 and at Month 48]
• Proportion of participants experiencing resolution of steatohepatitis on overall histopathological reading and improvement in liver fibrosis of >=1 stage at Week 52 [Срок оценки: At Week 52]
• Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of Steatohepatitis at Month 48 [Срок оценки: At Month 48]
• Proportion of participants experiencing improvement in fibrosis by >=2 stage and no worsening of Steatohepatitis at Week 52 and Month 48 [Срок оценки: At Week 52 and Month 48]
• Proportion of participants experiencing resolution of steatohepatitis reading and no worsening of MASH CRN score at Month 48 [Срок оценки: At Month 48]
• Absolute change from Baseline in vibration-controlled transient elastography-liver stiffness measurement (VCTE-LSM) [Срок оценки: Baseline (Day 1), Week 52 and Month 48]
• Percent change from Baseline in VCTE-LSM [Срок оценки: Baseline (Day 1), Week 52 and Month 48]
• Absolute change from Baseline in controlled attenuation parameter (CAP) scores [Срок оценки: Baseline (Day 1), Week 52 and Month 48]
• Percent change from Baseline in CAP scores [Срок оценки: Baseline (Day 1), Week 52 and Month 48]
• Proportion of participants achieving Change from Baseline in VCTE-LSM >=30 percent (%) at Week 52 and Month 48 [Срок оценки: Baseline (Day 1), Week 52 and Month 48]

Критерии участия

Критерии включения

• Able and willing to understand and sign a written informed consent form that must be obtained prior to the initiation of study procedures
• Age >=18 and <=75 years at enrollment
• History or presence of 2 or more of the 5 components of metabolic syndrome per American Heart Association definition
• Liver biopsy confirmation of MASH consistent with stage F2 or F3 fibrosis and a NAS score >=4 confirmed by a central pathologist

Критерии исключения

• Contraindication or ineligibility for percutaneous liver biopsy
• ALT or AST >=5 x upper limit of normal (ULN)
• Total bilirubin >=1.3 milligram per deciliter (mg/dL). Individuals with documented Gilbert's syndrome may be enrolled if they experienced an isolated increase in total bilirubin of >=1.3 mg/dL and direct bilirubin is <=20% of total bilirubin; otherwise, the individual will be excluded.
• Serum albumin <=3.5 grams per deciliter (g/dL)
• International normalized ratio (INR) >=1.3 not due to therapeutic anticoagulation. Individuals receiving chronic anticoagulant treatment with higher INR values may be enrolled at the discretion of the Investigator and Study Medical Monitor.
• Alkaline phosphatase (ALP) >=2\*ULN
• Platelet (PLT) count <140,000 per (/) cubic millimeter (mm\^3); individuals with a PLT count between 110,000/mm\^3 and 140,000/mm\^3 may be enrolled after discussion with the Study Medical Monitor.
• Serum creatinine >=1.5 mg/dL or creatinine clearance <=60 milliliter (mL)/minute (min)/1.73 square meter by Chronic Kidney Disease Epidemiology Collaboration equation
• Alpha-fetoprotein >=20 nanogram per milliliter (ng/mL)
• Glycated hemoglobin >=9.0%
• Model for End-Stage Liver Disease score >=12 unless the score is elevated in the absence of liver dysfunction (e.g., Gilbert's syndrome)
• Phosphatidyl ethanol (PEth) >=80 ng/mL at Screening
• Evidence of infection with any of the following:

• Human immunodeficiency virus;
• Hepatitis B virus (detectable HBsAg at Screening);
• Hepatitis C virus (HCV);
• Chronic liver disease from any other cause including, but not limited to, alcoholic liver disease; evidence of portal hypertension; viral hepatitis or any history or evidence of cirrhosis on screening liver biopsy; or decompensated liver disease such as clinical ascites, bleeding gastroesophageal varices, hepatorenal syndrome, or hepatic encephalopathy prior to Screening or Day 1.
• Current or history of excessive alcohol intake for >=3 months within the 12-month period prior to Screening

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 76 центров

• GSK Investigational Site — Chandler
• GSK Investigational Site — Tucson
• GSK Investigational Site — Little Rock
• GSK Investigational Site — Arcadia
• GSK Investigational Site — Covina
• GSK Investigational Site — Folsom
• GSK Investigational Site — Los Angeles
• GSK Investigational Site — Montclair
• … и ещё 68 центров

Япония · 5 центров

Список центров уточняется — проверьте первичный протокол.

Тайвань · 3 центра

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Австралия · 2 центра

• GSK Investigational Site — Broadmeadow
• GSK Investigational Site — Heidelberg

Канада · 1 центр

• GSK Investigational Site — Québec

Гонконг · 1 центр

• GSK Investigational Site — Pokfulam

Новая Зеландия · 1 центр

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Пуэрто-Рико · 1 центр

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Саудовская Аравия · 1 центр

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Идентификаторы

NCT: NCT07221227 · 301160 · 2025-523675-39

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗