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)

GlaxoSmithKline (GSK)

Status and phase: Enrolling; Phase 3

Conditions: Non-alcoholic Fatty Liver Disease

Treatments: Drug: Efimosfermin Alfa; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07221188

306246

2025-523674-16 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 1,250 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,250 participants in 3 patient groups, including a placebo group

Efimosfermin Alfa Dose Level 1

Experimental group

Description:

Participants randomized to this group will receive Efimosfermin Alfa at dose level 1

Treatment:

Drug: Efimosfermin Alfa

Efimosfermin Alfa Dose Level 2

Experimental group

Description:

Participants randomized to this group will receive Efimosfermin Alfa at dose level 2

Treatment:

Drug: Efimosfermin Alfa

Placebo

Placebo Comparator group

Description:

Participants randomized to this group will receive Placebo

Treatment:

Drug: Placebo