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Recruiting NCT07221227

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

Phase III Interventional Non-alcoholic Fatty Liver Disease

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Efimosfermin alfa, Efimosfermin alfa, Placebo.
Who it may be relevant to
Registry conditions: Non-alcoholic Fatty Liver Disease. Basic parameters: 18 years — 75 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Australia, Canada, Hong Kong, Japan +4
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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)

Overview

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.

Interventions

  • Drug Efimosfermin alfa
    Efimosfermin alfa will be administered
  • Drug Efimosfermin alfa
    Efimosfermin alfa will be administered
  • Drug Placebo
    Placebo will be administered

Primary outcome measures

  • Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of steatohepatitis at Week 52 [Time frame: At Week 52]
  • Proportion of participants experiencing resolution of steatohepatitis reading and no worsening of MASH CRN fibrosis score at Week 52 [Time frame: At Week 52]
  • Time from randomization to an adjudicated composite liver-related clinical outcome [Time frame: From Randomization (Day 1) to 48 months]
Secondary outcome measures (12)
  • Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity [Time frame: At Week 52 and at Month 48]
  • Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity [Time frame: At Week 52 and at Month 48]
  • Number of participants with Grade 3 and Grade 4 laboratory abnormalities [Time frame: 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 [Time frame: At Week 52]
  • Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of Steatohepatitis at Month 48 [Time frame: At Month 48]
  • Proportion of participants experiencing improvement in fibrosis by >=2 stage and no worsening of Steatohepatitis at Week 52 and Month 48 [Time frame: At Week 52 and Month 48]
  • Proportion of participants experiencing resolution of steatohepatitis reading and no worsening of MASH CRN score at Month 48 [Time frame: At Month 48]
  • Absolute change from Baseline in vibration-controlled transient elastography-liver stiffness measurement (VCTE-LSM) [Time frame: Baseline (Day 1), Week 52 and Month 48]
  • Percent change from Baseline in VCTE-LSM [Time frame: Baseline (Day 1), Week 52 and Month 48]
  • Absolute change from Baseline in controlled attenuation parameter (CAP) scores [Time frame: Baseline (Day 1), Week 52 and Month 48]
  • Percent change from Baseline in CAP scores [Time frame: 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 [Time frame: Baseline (Day 1), Week 52 and Month 48]

Eligibility criteria

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Double blind
Primary purpose
Treatment

Study locations

United States · 76 centers
  • 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
  • … and 68 more centers
Japan · 5 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 3 centers

Center list to be confirmed — check the primary protocol.

Australia · 2 centers
  • GSK Investigational Site — Broadmeadow
  • GSK Investigational Site — Heidelberg
Canada · 1 center
  • GSK Investigational Site — Québec
Hong Kong · 1 center
  • GSK Investigational Site — Pokfulam
New Zealand · 1 center

Center list to be confirmed — check the primary protocol.

Puerto Rico · 1 center

Center list to be confirmed — check the primary protocol.

Saudi Arabia · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07221227 · 301160 · 2025-523675-39

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗