Last updated: 10/24/2025 15:00:06

A clinical study to investigate the safety and tolerability of efimosfermin alfa injection in participants with known or suspected F2- or F3-stage MASHZENITH-2

GSK study ID
306246
Clinicaltrials.gov ID
Not applicable
EudraCT ID
Not applicable
EU CT Number
2025-523674-16
Trial status
Will be recruiting
Will be recruiting
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: 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)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity

Timeframe: At Week 52

Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity

Timeframe: At Week 52

Number of participants with Grade 3 and Grade 4 laboratory abnormalities

Timeframe: At Week 52

Secondary outcomes:

Absolute Change from Baseline in enhanced liver fibrosis (ELF) score

Timeframe: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in ELF score

Timeframe: Baseline (Day 1) and up to Week 52

Number of participants achieving an improvement in ELF score greater than equal to 0.5

Timeframe: At Week 52

Absolute Change from Baseline in vibration-controlled transient elastography (VCTE)- liver stiffness measurement (LSM) scores

Timeframe: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in VCTE- LSM scores

Timeframe: Baseline (Day 1) and up to Week 52

Number of participants achieving a change from Baseline in VCTE-LSM >=30 percentage (%)

Timeframe: Baseline (Day 1) and up to Week 52

Absolute Change from Baseline in magnetic resonance elastography (MRE) scores in the subset of participants

Timeframe: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in the subset of participants with magnetic resonance elastography (MRE) scores

Timeframe: 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)

Timeframe: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in HFF by MRI-PDFF

Timeframe: Baseline (Day 1) and up to Week 52

Absolute Change from Baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (International units per liter)

Timeframe: Baseline (Day 1) and up to Week 52

Absolute Change from Baseline in ALT and AST ratio (ALT/AST)

Timeframe: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in ALT and AST (International units per liter)

Timeframe: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in ALT and AST ratio (ALT/AST)

Timeframe: Baseline (Day 1) and up to Week 52

Number of participants achieving ALT and HFF normalization

Timeframe: At Week 52

Number of participants achieving HFF less than equal to (<=) 5%

Timeframe: At Week 52

Change from Baseline in glycated hemoglobin (HbA1c) for participants with type 2 diabetes mellitus (T2DM)

Timeframe: Baseline (Day 1) and up to Week 52

Change from Baseline in body weight for all participants(kilograms)

Timeframe: 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)

Timeframe: 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

Timeframe: At Week 52

Maximum serum drug concentrations (Cmax) of efimosfermin alfa

Timeframe: Up to Week 52

Area under the serum concentration-time curve (AUC) of efimosfermin alfa

Timeframe: Up to Week 52

Average serum drug concentration (Cavg) of efimosfermin alfa

Timeframe: Up to Week 52

Serum concentration of study drug at the end of the dosing interval (Ctrough) of efimosfermin alfa

Timeframe: Up to Week 52

Exposure-response relationship for efimosfermin alfa

Timeframe: Baseline (Day 1) and up to Week 52

Interventions:
  • Drug: Efimosfermin Alfa
  • Drug: Placebo
    • Enrollment:
    1250
    Primary completion date:
    2028-24-03
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Non-alcoholic Fatty Liver Disease
    Product
    Not applicable
    Collaborators
    Not applicable
    Study date(s)
    October 2025 to March 2028
    Type
    Interventional
    Phase
    3

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 75 Years
    Accepts healthy volunteers
    No
    • 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
    • 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.
    Inclusion and exclusion criteria
    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
    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.
      • 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

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    No study documents available.

    Results overview

    Study Results yet to be posted

    Recruitment status
    Will be recruiting
    Actual primary completion date
    Not applicable
    Actual study completion date
    Not applicable

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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