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Efimosfermin alfa for adults with biopsy-confirmed F2 or F3 MASH

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study to Investigate the Safety and Efficacy of Efimosfermin Alfa in Participants With Biopsy-Confirmed F2- or F3-Stage Metabolic Dysfunction-Associated Steatohepatitis (MASH) (ZENITH-1)

Phase 3 Interventional GlaxoSmithKline · NCT07221227

This trial will test whether efimosfermin alfa can resolve steatohepatitis and improve liver-related outcomes in adults with biopsy-confirmed F2 or F3 MASH.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1200 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorGlaxoSmithKline Industry-sponsored
Locations49 sites (Arcadia, California and 48 other locations)
Trial IDNCT07221227 on ClinicalTrials.gov

What this trial studies

This Phase 3 study enrolls adults aged 18–75 with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and stage F2 or F3 fibrosis. Eligible participants must have a NAS score ≥4 confirmed by a central pathologist and at least two components of metabolic syndrome. Participants will be assigned to receive efimosfermin alfa or placebo and followed for liver-related outcomes and safety. Study procedures include baseline liver biopsy confirmation and regular clinical and laboratory assessments at GSK investigational sites in California.

Who should consider this trial

Good fit: Adults aged 18–75 with biopsy-confirmed MASH at fibrosis stage F2 or F3, NAS ≥4, and at least two metabolic syndrome components are the intended participants.

Not a fit: People with cirrhosis (F4), marked liver dysfunction (very high ALT/AST, low albumin, elevated INR), inability to undergo biopsy, or other excluded conditions are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, efimosfermin alfa could offer a new medical therapy that resolves steatohepatitis and slows progression toward cirrhosis in people with F2–F3 MASH.

How similar studies have performed: Early-phase trials of efimosfermin alfa and related metabolic agents have shown promising signals for improving steatohepatitis, but phase 3 confirmation is still needed.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Able and willing to understand and sign a written informed consent form that must be obtained prior to the initiation of study procedures
2. Age \>=18 and \<=75 years at enrollment
3. History or presence of 2 or more of the 5 components of metabolic syndrome per American Heart Association definition
4. Liver biopsy confirmation of MASH consistent with stage F2 or F3 fibrosis and a NAS score \>=4 confirmed by a central pathologist

Exclusion Criteria:

1. Contraindication or ineligibility for percutaneous liver biopsy
2. ALT or AST \>=5 x upper limit of normal (ULN)
3. Total bilirubin \>=1.3 milligram per deciliter (mg/dL). Individuals with documented Gilbert's syndrome may be enrolled if they experienced an isolated increase in total bilirubin of \>=1.3 mg/dL and direct bilirubin is \<=20% of total bilirubin; otherwise, the individual will be excluded.
4. Serum albumin \<=3.5 grams per deciliter (g/dL)
5. 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.
6. Alkaline phosphatase (ALP) \>=2\*ULN
7. 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.
8. 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
9. Alpha-fetoprotein \>=20 nanogram per milliliter (ng/mL)
10. Glycated hemoglobin \>=9.0%
11. Model for End-Stage Liver Disease score \>=12 unless the score is elevated in the absence of liver dysfunction (e.g., Gilbert's syndrome)
12. Phosphatidyl ethanol (PEth) \>=80 ng/mL at Screening
13. Evidence of infection with any of the following:

    1. Human immunodeficiency virus;
    2. Hepatitis B virus (detectable HBsAg at Screening);
    3. Hepatitis C virus (HCV);
14. 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 on screening liver biopsy; or decompensated liver disease such as clinical ascites, bleeding gastroesophageal varices, hepatorenal syndrome, or hepatic encephalopathy prior to Screening or Day 1.
15. Current or history of excessive alcohol intake for \>=3 months within the 12-month period prior to Screening

Where this trial is running

Arcadia, California and 48 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-alcoholic Fatty Liver DiseaseEfimosfermin AlfaMetabolic Dysfunction-Associated SteatohepatitisZENITH-1
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.