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Efimosfermin alfa injections for adults with F2–F3 MASH

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)

Phase 3 Interventional GlaxoSmithKline · NCT07221188

This study tests whether efimosfermin alfa injections are safe and tolerable for adults (18–75) with known or suspected metabolic dysfunction-associated steatohepatitis (MASH) and F2–F3 fibrosis.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1250 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorGlaxoSmithKline Industry-sponsored
Locations43 sites (Arcadia, California and 42 other locations)
Trial IDNCT07221188 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial enrolls adults aged 18–75 with known or suspected MASH and fibrosis consistent with stage F2 or F3. Participants receive efimosfermin alfa injections or a matching placebo and are monitored during the treatment period with regular labs and clinical assessments to record safety and tolerability outcomes. Key inclusion criteria require at least two components of metabolic syndrome, while exclusion criteria include very high liver enzymes, elevated bilirubin, low albumin, or abnormal INR. The trial is run at GSK investigational sites in Southern California and is focused on collecting adverse event, laboratory, and tolerability data to support further development.

Who should consider this trial

Good fit: Adults 18–75 with known or suspected MASH and fibrosis stage F2 or F3 who have at least two features of metabolic syndrome and meet the study's liver and laboratory criteria.

Not a fit: People with very high transaminases, elevated total bilirubin, low serum albumin, significant INR abnormalities, or those outside the 18–75 age range are unlikely to be eligible or to benefit from this safety-focused trial.

Why it matters

Potential benefit: If successful, this could identify a safe and tolerable treatment approach that enables later studies to test whether efimosfermin improves liver disease in people with F2–F3 MASH.

How similar studies have performed: Earlier-phase trials of efimosfermin provided enough safety and tolerability data to advance to Phase 3, but large-scale clinical benefit in MASH has not yet been proven.

Eligibility criteria

Show full inclusion / 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 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

Where this trial is running

Arcadia, California and 42 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 DiseaseMetabolic Dysfunction-Associated Steatohepatitisefimosfermin alfaSafetyTolerabilityPhase 3ZENITH-2
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.