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

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)

Overview

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.

Interventions

• Drug Efimosfermin Alfa
  Efimosfermin Alfa will be administered
• Drug Placebo
  Placebo will be administered

Primary outcome measures

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

Secondary outcome measures (12)

• Absolute Change from Baseline in enhanced liver fibrosis (ELF) score [Time frame: 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]
• Number of participants achieving an improvement in ELF score greater than equal to 0.5 [Time frame: 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]
• Percent Change from Baseline in VCTE- LSM scores [Time frame: 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]
• 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]
• 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]
• 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]
• Percent Change from Baseline in HFF by MRI-PDFF [Time frame: 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]
• Absolute Change from Baseline in ALT and AST ratio (ALT/AST) [Time frame: Baseline (Day 1) and up to Week 52]

Eligibility 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 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 52 centers

• GSK Investigational Site — Arcadia
• GSK Investigational Site — Covina
• GSK Investigational Site — Los Angeles
• GSK Investigational Site — San Diego
• GSK Investigational Site — Santa Maria
• GSK Investigational Site — Van Nuys
• GSK Investigational Site — Boynton Beach
• GSK Investigational Site — Cape Coral
• … and 44 more centers

Hong Kong · 1 center

• GSK Investigational Site — Pokfulam

Identifiers

NCT: NCT07221188 · 306246 · 2025-523674-16

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗