Last updated: 06/25/2026 16:11:03
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
EudraCT ID
Not applicable
EU CT Number
Trial status
Recruiting
Recruiting
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
Serum drug Concentration of efimosfermin alfa
Timeframe: Up to Week 52
Interventions:
Drug: Efimosfermin Alfa
Drug: Placebo
Enrollment:
1250
Observational study model:
Not applicable
Primary completion date:
2028-24-03
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Non-alcoholic Fatty Liver Disease
Product
Not applicable
Collaborators
Not applicable
Study date(s)
December 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:
- 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
Able and willing to understand and sign a written informed consent form (ICF) that must be obtained prior to the initiation of study procedures
Exclusion criteria:
- 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
ALT or AST >=5 × upper limit of normal (ULN)
Trial location(s)
Location
GSK Investigational Site
Boynton Beach, Florida, United States, 33435
Status
Recruiting
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
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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