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

RecruitingPhase 3

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)

Who can join

Ages 18 to 75 · All sexes

Full eligibility criteria
Inclusion Criteria:

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

Exclusion Criteria:

1. Contraindication or ineligibility for percutaneous liver biopsy
2. ALT or AST \>=5 x upper limit of normal (ULN)
3. 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.
4. Serum albumin \<=3.5 grams per deciliter (g/dL)
5. 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.
6. Alkaline phosphatase (ALP) \>=2\*ULN
7. 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.
8. 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
9. Alpha-fetoprotein \>=20 nanogram per milliliter (ng/mL)
10. Glycated hemoglobin \>=9.0%
11. Model for End-Stage Liver Disease score \>=12 unless the score is elevated in the absence of liver dysfunction (e.g., Gilbert's syndrome)
12. Phosphatidyl ethanol (PEth) \>=80 ng/mL at Screening
13. Evidence of infection with any of the following:

    1. Human immunodeficiency virus;
    2. Hepatitis B virus (detectable HBsAg at Screening);
    3. Hepatitis C virus (HCV);
14. 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.
15. Current or history of excessive alcohol intake for \>=3 months within the 12-month period prior to Screening

About the study

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.

What is being tested

Sponsor: GlaxoSmithKline · Participants: 1,200 · Started: Oct 24, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT07221227

Locations in the U.S.

ArizonaGSK Investigational Site, Chandler
GSK Investigational Site, Tucson
ArkansasGSK Investigational Site, Little Rock
CaliforniaGSK Investigational Site, Arcadia
GSK Investigational Site, Covina
GSK Investigational Site, Folsom
GSK Investigational Site, Los Angeles
GSK Investigational Site, Montclair
GSK Investigational Site, Riverdale
GSK Investigational Site, San Diego
GSK Investigational Site, Santa Maria
GSK Investigational Site, Van Nuys
ColoradoGSK Investigational Site, Colorado Springs
FloridaGSK Investigational Site, Boynton Beach
GSK Investigational Site, Cape Coral
GSK Investigational Site, Clermont
GSK Investigational Site, Fort Myers
GSK Investigational Site, Hialeah
GSK Investigational Site, Hialeah
GSK Investigational Site, Homestead
GSK Investigational Site, Inverness
GSK Investigational Site, Jacksonville
GSK Investigational Site, Kissimmee
GSK Investigational Site, Lakeland
GSK Investigational Site, Maitland
GSK Investigational Site, Miami
GSK Investigational Site, Miami
GSK Investigational Site, Miami
GSK Investigational Site, Miami
GSK Investigational Site, Miami
GSK Investigational Site, Miami
GSK Investigational Site, Miami
GSK Investigational Site, Miami Lakes
GSK Investigational Site, Ocala
GSK Investigational Site, Palmetto Bay
GSK Investigational Site, Sarasota
GeorgiaGSK Investigational Site, Marietta
KansasGSK Investigational Site, Topeka
LouisianaGSK Investigational Site, Bastrop
GSK Investigational Site, Marrero
MissouriGSK Investigational Site, Kansas City
GSK Investigational Site, Springfield
GSK Investigational Site, St Louis
NevadaGSK Investigational Site, Las Vegas
New YorkGSK Investigational Site, East Syracuse
GSK Investigational Site, New York
GSK Investigational Site, New York
North CarolinaGSK Investigational Site, Fayetteville
GSK Investigational Site, Morehead City
OhioGSK Investigational Site, Akron
GSK Investigational Site, Springboro
GSK Investigational Site, Westlake
TennesseeGSK Investigational Site, Chattanooga
TexasGSK Investigational Site, Arlington
GSK Investigational Site, Austin
GSK Investigational Site, Austin
GSK Investigational Site, Austin
GSK Investigational Site, Bellaire
GSK Investigational Site, Brownsville
GSK Investigational Site, Dallas
GSK Investigational Site, DeSoto
GSK Investigational Site, Houston
GSK Investigational Site, Irving
GSK Investigational Site, Richmond
GSK Investigational Site, San Antonio
GSK Investigational Site, San Antonio
GSK Investigational Site, San Antonio
GSK Investigational Site, Seabrook
GSK Investigational Site, Sugar Land
GSK Investigational Site, Tomball
GSK Investigational Site, Waco
GSK Investigational Site, Waco
UtahGSK Investigational Site, West Jordan
VirginiaGSK Investigational Site, Manassas
GSK Investigational Site, Norfolk
WashingtonGSK Investigational Site, Seattle

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.