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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified February 2026 by GlaxoSmithKline
Sponsor
GlaxoSmithKline
Information Provided by (Responsible Party)
GlaxoSmithKline
Clinicaltrials.gov Identifier
NCT07221188
Other Study ID Numbers:
306246
First Submitted
October 14, 2025
First Posted
October 26, 2025
Last Update Posted
April 15, 2026
Last Verified
February 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Non-alcoholic Fatty Liver Disease
Drug: Efimosfermin AlfaDrug: Efimosfermin AlfaDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment1250 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA 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)
Study Start DateDecember 11, 2025
Actual Primary Completion Date1yr 9mos from now
Actual Study Completion Date1yr 9mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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
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
Participants randomized to this group will receive Placebo
Drug: Placebo
Placebo will be administered

Outcome Measures

Primary Outcome Measures
  1. Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity
  2. Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity
  3. Number of participants with Grade 3 and Grade 4 laboratory abnormalities
Secondary Outcome Measures
  1. Absolute Change from Baseline in enhanced liver fibrosis (ELF) score
    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.
  2. Percent Change from Baseline in ELF score
    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.
  3. Number of participants achieving an improvement in ELF score greater than equal to 0.5
    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.
  4. Absolute Change from Baseline in vibration-controlled transient elastography (VCTE)- liver stiffness measurement (LSM) scores
  5. Percent Change from Baseline in VCTE- LSM scores
  6. Number of participants achieving a change from Baseline in VCTE-LSM >=30 percentage (%)
  7. Absolute Change from Baseline in magnetic resonance elastography (MRE) scores in the subset of participants
    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.
  8. Percent Change from Baseline in the subset of participants with magnetic resonance elastography (MRE) scores
    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.
  9. Absolute Change from Baseline in hepatic fat fraction (HFF) by magnetic resonance imaging (MRI)- derived proton density fat fraction (PDFF)
    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.
  10. Percent Change from Baseline in HFF by MRI-PDFF
    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.
  11. Absolute Change from Baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (International units per liter)
  12. Absolute Change from Baseline in ALT and AST ratio (ALT/AST)
  13. Percent Change from Baseline in ALT and AST (International units per liter)
  14. Percent Change from Baseline in ALT and AST ratio (ALT/AST)
  15. Number of participants achieving ALT and HFF normalization
  16. Number of participants achieving HFF less than equal to (<=) 5%
    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.
  17. Change from Baseline in glycated hemoglobin (HbA1c) for participants with type 2 diabetes mellitus (T2DM)
  18. Change from Baseline in body weight for all participants(kilograms)
  19. Change from Baseline in fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)- cholesterol, and fasting triglycerides (Millimoles per liter)
  20. Number of Participants with antidrug and anti-fibroblast growth factor 21 (FGF21) antibodies (ADA) at Week 52
  21. Serum drug Concentration of efimosfermin alfa

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsGlaxoSmithKline
Locations
GSK Investigational Site | Arcadia California, United States, 91006GSK Investigational Site | Covina California, United States, 91723GSK Investigational Site | Los Angeles California, United States, 90057GSK Investigational Site | Santa Maria California, United States, 93458GSK Investigational Site | Cape Coral Florida, United States, 33914GSK Investigational Site | Doral Florida, United States, 33016GSK Investigational Site | Hialeah Florida, United States, 33016GSK Investigational Site | Inverness Florida, United States, 34452GSK Investigational Site | Jacksonville Florida, United States, 32216GSK Investigational Site | Kissimmee Florida, United States, 34744GSK Investigational Site | Lakeland Florida, United States, 33803GSK Investigational Site | Maitland Florida, United States, 32751GSK Investigational Site | Miami Florida, United States, 33135GSK Investigational Site | Miami Florida, United States, 33155GSK Investigational Site | Miami Florida, United States, 33156GSK Investigational Site | Miami Florida, United States, 33184GSK Investigational Site | Miami Lakes Florida, United States, 33014GSK Investigational Site | Ocala Florida, United States, 34471GSK Investigational Site | Palmetto Bay Florida, United States, 33157GSK Investigational Site | Topeka Kansas, United States, 66606GSK Investigational Site | Springfield Missouri, United States, 62703GSK Investigational Site | St Louis Missouri, United States, 63141GSK Investigational Site | Jersey City New Jersey, United States, 07059GSK Investigational Site | East Syracuse New York, United States, 13057GSK Investigational Site | New York New York, United States, 10036GSK Investigational Site | Morehead City North Carolina, United States, 28557GSK Investigational Site | Akron Ohio, United States, 44320GSK Investigational Site | Springboro Ohio, United States, 45066GSK Investigational Site | Austin Texas, United States, 78745GSK Investigational Site | Austin Texas, United States, 78759GSK Investigational Site | Brownsville Texas, United States, 78526GSK Investigational Site | Dallas Texas, United States, 75243GSK Investigational Site | DeSoto Texas, United States, 75115GSK Investigational Site | Richmond Texas, United States, 77406GSK Investigational Site | San Antonio Texas, United States, 78215GSK Investigational Site | San Antonio Texas, United States, 78229GSK Investigational Site | Seabrook Texas, United States, 77586GSK Investigational Site | Tomball Texas, United States, 77375GSK Investigational Site | Waco Texas, United States, 76710GSK Investigational Site | Waco Texas, United States, 76712GSK Investigational Site | West Jordan Utah, United States, 84088GSK Investigational Site | Manassas Virginia, United States, 20110GSK Investigational Site | Seattle Washington, United States, 98105
Investigators
Study Director: GSK Clinical Trials, GlaxoSmithKline