A Clinical Study to Investigate the Safety and Tolerability of Efimosfermin Alfa Injection in Participants With Known or Suspected F2- or F3-stage MASH (ZENITH-2)

April 13, 2026 updated by: GlaxoSmithKline

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study to Investigate the Safety and Tolerability of Efimosfermin Alfa in Participants With Known or Suspected F2- or F3-Stage Metabolic Dysfunction-Associated Steatohepatitis (MASH) (ZENITH-2)

This study will evaluate the safety and tolerability of Efimosfermin Alfa for participants with known or suspected MASH with fibrosis consistent with stage F2 or F3.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

1250

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Arcadia, California, United States, 91006
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Elias Tarakji
      • Covina, California, United States, 91723
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Masoud Azizad
      • Los Angeles, California, United States, 90057
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Joseph Lamb
      • Santa Maria, California, United States, 93458
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Keval Shah
    • Florida
      • Cape Coral, Florida, United States, 33914
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Paige Kreegel
      • Doral, Florida, United States, 33016
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jorge Diaz
      • Hialeah, Florida, United States, 33016
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Isaac Bassan, MD
        • Contact:
        • Contact:
      • Inverness, Florida, United States, 34452
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Paul Hellstern Jr.
      • Jacksonville, Florida, United States, 32216
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jeffry Jacqmein
      • Kissimmee, Florida, United States, 34744
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Luis Alvarado
      • Lakeland, Florida, United States, 33803
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • James Andersen
      • Maitland, Florida, United States, 32751
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Principal Investigator:
          • Eva Maria Heurich
        • Contact:
      • Miami, Florida, United States, 33155
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • JORGE AMAYA
        • Contact:
        • Contact:
      • Miami, Florida, United States, 33156
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lazaro M Garcia
      • Miami, Florida, United States, 33135
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yaneicy Gonzalez Rojas
      • Miami, Florida, United States, 33184
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Franciso Bautista
      • Miami Lakes, Florida, United States, 33014
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Miguel Aponte
      • Ocala, Florida, United States, 34471
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Robert Barish
        • Contact:
        • Contact:
      • Palmetto Bay, Florida, United States, 33157
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Karen Figueredo Reyes
    • Kansas
      • Topeka, Kansas, United States, 66606
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Shekhar Challa
        • Contact:
        • Contact:
    • Missouri
      • Springfield, Missouri, United States, 62703
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Dmitry Shuster
      • St Louis, Missouri, United States, 63141
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Fred Williams
    • New Jersey
      • Jersey City, New Jersey, United States, 07059
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Samar Hameed
    • New York
      • East Syracuse, New York, United States, 13057
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Barbara Connor
      • New York, New York, United States, 10036
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Eli Shalenberg
    • North Carolina
      • Morehead City, North Carolina, United States, 28557
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Kathryn Lucas
        • Contact:
        • Contact:
    • Ohio
      • Akron, Ohio, United States, 44320
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ganesh Veerappan
      • Springboro, Ohio, United States, 45066
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Anjali Morey
    • Texas
      • Austin, Texas, United States, 78745
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Nomita Kim
      • Austin, Texas, United States, 78759
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Michael Patrick Zimmerman
      • Brownsville, Texas, United States, 78526
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Christopher Romero
        • Contact:
        • Contact:
      • Dallas, Texas, United States, 75243
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Valentine Ebuh
      • DeSoto, Texas, United States, 75115
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • HARESH BOGHARA
      • Richmond, Texas, United States, 77406
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Brian Chou
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Emanuel DeNoia
      • San Antonio, Texas, United States, 78215
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Eric Lawitz
        • Contact:
        • Contact:
      • Seabrook, Texas, United States, 77586
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Joe Pouzar
      • Tomball, Texas, United States, 77375
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Muhammad Irfan
      • Waco, Texas, United States, 76712
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Hanumantha Ancha
      • Waco, Texas, United States, 76710
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Gregg Lucksinger
        • Contact:
        • Contact:
    • Utah
      • West Jordan, Utah, United States, 84088
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Barbara Rizzardi
    • Virginia
      • Manassas, Virginia, United States, 20110
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Nabil Andrawis
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Kris Kowdley
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Able and willing to understand and sign a written informed consent form (ICF) that must be obtained prior to the initiation of study procedures
  • Age >=18 through <=75 years at enrolment
  • History or presence of 2 or more of the 5 components of metabolic syndrome per American Heart Association definition
  • History or presence of known or suspected MASH with evidence of fibrosis

Exclusion Criteria:

  • ALT or AST >=5 × upper limit of normal (ULN)
  • Total bilirubin (BILI) >=1.3 milligram per deciliter (mg/dL). Individuals with documented Gilbert's syndrome may be enrolled if they experienced an isolated increase in total BILI of >=1.3 mg/dL and direct BILI is <=20% of total BILI; 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)
  • HbA1c >=9.0%
  • Model for End-Stage Liver Disease (MELD) 3.0 score >=12 unless the score is elevated in the absence of liver dysfunction (eg, Gilbert's syndrome)
  • Phosphatidylethanol (PEth) >=80 nanogram per milliliter (ng/mL) at Screening
  • Known co-infection with any of the following: a. Human immunodeficiency virus; b. Hepatitis B virus; c. Hepatitis C virus (HCV); d. Hepatitis D virus; or e. Hepatitis E virus.
  • 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; 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Efimosfermin Alfa Dose Level 1
Participants randomized to this group will receive Efimosfermin Alfa at dose level 1
Drug: Efimosfermin Alfa
Efimosfermin Alfa will be administered
Experimental: Efimosfermin Alfa Dose Level 2
Participants randomized to this group will receive Efimosfermin Alfa at dose level 2
Drug: Efimosfermin Alfa
Efimosfermin Alfa will be administered
Placebo Comparator: Placebo
Participants randomized to this group will receive Placebo
Drug: Placebo
Placebo will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity
Time Frame: At Week 52
At Week 52
Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity
Time Frame: At Week 52
At Week 52
Number of participants with Grade 3 and Grade 4 laboratory abnormalities
Time Frame: At Week 52
At Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change from Baseline in enhanced liver fibrosis (ELF) score
Time Frame: Baseline (Day 1) and up to Week 52
The ELF score will be calculated using a published algorithm combining the values of a set of extracellular matrix markers. The ELF score is used as a prognostic marker for disease progression: ELF score less than (<) 9.8: Low risk of progression, ELF score 9.8 to <11.3: Moderate risk of progression and ELF score greater than or equal to (>=) 11.3: High risk of progression.
Baseline (Day 1) and up to Week 52
Percent Change from Baseline in ELF score
Time Frame: Baseline (Day 1) and up to Week 52
The ELF score will be calculated using a published algorithm combining the values of a set of extracellular matrix markers. The ELF score is used as a prognostic marker for disease progression: ELF score <9.8: Low risk of progression, ELF score 9.8 to <11.3: Moderate risk of progression and ELF score >=11.3: High risk of progression.
Baseline (Day 1) and up to Week 52
Number of participants achieving an improvement in ELF score greater than equal to 0.5
Time Frame: At Week 52
The ELF score will be calculated using a published algorithm combining the values of a set of extracellular matrix markers. The ELF score is used as a prognostic marker for disease progression: ELF score <9.8: Low risk of progression, ELF score 9.8 to <11.3: Moderate risk of progression and ELF score >=11.3: High risk of progression.
At Week 52
Absolute Change from Baseline in vibration-controlled transient elastography (VCTE)- liver stiffness measurement (LSM) scores
Time Frame: Baseline (Day 1) and up to Week 52
Baseline (Day 1) and up to Week 52
Percent Change from Baseline in VCTE- LSM scores
Time Frame: Baseline (Day 1) and up to Week 52
Baseline (Day 1) and up to Week 52
Number of participants achieving a change from Baseline in VCTE-LSM >=30 percentage (%)
Time Frame: Baseline (Day 1) and up to Week 52
Baseline (Day 1) and up to Week 52
Absolute Change from Baseline in magnetic resonance elastography (MRE) scores in the subset of participants
Time Frame: Baseline (Day 1) and up to Week 52
MRE is a non-invasive imaging technique that combine magnetic resonance imaging (MRI) scanning with low-frequency mechanical vibrations to measure the stiffness of liver. MRE scores <2.5 is normal, 2.5 - 3.0 Normal or inflammation, 3.0 - 3.5 Stage 1-2 fibrosis, 3.5 - 4.0 Stage 2-3 fibrosis, 4.0 - 5.0 Stage 3-4 fibrosis and > 5.0 Stage 4 fibrosis.
Baseline (Day 1) and up to Week 52
Percent Change from Baseline in the subset of participants with magnetic resonance elastography (MRE) scores
Time Frame: Baseline (Day 1) and up to Week 52
MRE is a non-invasive imaging technique that combine MRI scanning with low-frequency mechanical vibrations to measure the stiffness of liver. MRE scores <2.5 is normal, 2.5 - 3.0 Normal or inflammation, 3.0 - 3.5 Stage 1-2 fibrosis, 3.5 - 4.0 Stage 2-3 fibrosis, 4.0 - 5.0 Stage 3-4 fibrosis and > 5.0 Stage 4 fibrosis.
Baseline (Day 1) and up to Week 52
Absolute Change from Baseline in hepatic fat fraction (HFF) by magnetic resonance imaging (MRI)- derived proton density fat fraction (PDFF)
Time Frame: Baseline (Day 1) and up to Week 52
HFF is the percentage of fat in the liver measured by MRI proton density fat fraction technique, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver.
Baseline (Day 1) and up to Week 52
Percent Change from Baseline in HFF by MRI-PDFF
Time Frame: Baseline (Day 1) and up to Week 52
HFF is the percentage of fat in the liver measured by MRI proton density fat fraction technique, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver.
Baseline (Day 1) and up to Week 52
Absolute Change from Baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (International units per liter)
Time Frame: Baseline (Day 1) and up to Week 52
Baseline (Day 1) and up to Week 52
Absolute Change from Baseline in ALT and AST ratio (ALT/AST)
Time Frame: Baseline (Day 1) and up to Week 52
Baseline (Day 1) and up to Week 52
Percent Change from Baseline in ALT and AST (International units per liter)
Time Frame: Baseline (Day 1) and up to Week 52
Baseline (Day 1) and up to Week 52
Percent Change from Baseline in ALT and AST ratio (ALT/AST)
Time Frame: Baseline (Day 1) and up to Week 52
Baseline (Day 1) and up to Week 52
Number of participants achieving ALT and HFF normalization
Time Frame: At Week 52
At Week 52
Number of participants achieving HFF less than equal to (<=) 5%
Time Frame: At Week 52
HFF is the percentage of fat in the liver measured by MRI proton density fat fraction technique, which ranges from 0-75%. Less than or equal to 5% is considered normal (no significant fatty infiltration (steatosis) in the liver.
At Week 52
Change from Baseline in glycated hemoglobin (HbA1c) for participants with type 2 diabetes mellitus (T2DM)
Time Frame: Baseline (Day 1) and up to Week 52
Baseline (Day 1) and up to Week 52
Change from Baseline in body weight for all participants(kilograms)
Time Frame: Baseline (Day 1) and up to Week 52
Baseline (Day 1) and up to Week 52
Change from Baseline in fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)- cholesterol, and fasting triglycerides (Millimoles per liter)
Time Frame: Baseline (Day 1) and up to Week 52
Baseline (Day 1) and up to Week 52
Number of Participants with antidrug and anti-fibroblast growth factor 21 (FGF21) antibodies (ADA) at Week 52
Time Frame: At Week 52
At Week 52
Serum drug Concentration of efimosfermin alfa
Time Frame: Up to Week 52
Up to Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2025

Primary Completion (Estimated)

March 24, 2028

Study Completion (Estimated)

March 24, 2028

Study Registration Dates

First Submitted

October 15, 2025

First Submitted That Met QC Criteria

October 24, 2025

First Posted (Actual)

October 27, 2025

Study Record Updates

Last Update Posted (Actual)

April 16, 2026

Last Update Submitted That Met QC Criteria

April 13, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 306246
  • 2025-523674-16 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf

IPD Sharing Time Frame

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

IPD Sharing Access Criteria

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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