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)

Investigational Treatment for Liver Condition Involving Fat and Inflammation (MASH)

R
Raj Vuppalanchi, MD

Primary Investigator

Enrolling By Invitation
18 years - 75 years
All
Phase 3
1 participants needed
1 Location

Brief description of study

The purpose of this study is to assess the safety and efficacy of efimosfermin alfa in the resolution of steatohepatitis and improvement of liver-related clinical outcome compared to placebo in individuals with MASH and biopsy-confirmed F2- or F3-stage fibrosis.

THIS STUDY IS ENROLLING BY INVITATION ONLY

Detailed description of study

This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, 48-month study of the safety and efficacy of efimosfermin administered every 4 weeks (Q4W) by subcutaneous (SC) injection in adult MASH participants with fibrosis that is consistent with stage F2 or F3. The total time of participation in the study, inclusive of

Screening and safety follow-up, is approximately 52 months.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Non-alcoholic Fatty Liver Disease
  • Age: 18 years - 75 years
  • Gender: All

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*upper limit of normal (ULN)
  3. 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.
  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. Known co-infection with any of the following:
    1. Human immunodeficiency virus;
    2. Hepatitis B virus;
    3. Hepatitis C virus (HCV);
    4. Hepatitis D virus; or
    5. Hepatitis E virus.
  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

This study investigates the safety and effects of an investigational medication for people with Metabolic Dysfunction-Associated Steatohepatitis (MASH) and liver fibrosis at stages F2 or F3. MASH is a liver condition where fat builds up in the liver, causing inflammation and damage. The purpose of this study is to see if the investigational medication can help resolve the inflammation and improve liver health compared to a placebo, which is a substance that looks like the investigational medication but has no active ingredients.

Participants in this study will receive the investigational medication or a placebo through a shot under the skin every four weeks. The study will compare the effects of the investigational medication with the placebo to understand its safety and effectiveness. The study involves regular check-ups and tests to monitor liver health and overall well-being.

  • Who can participate: Adults aged 18 to 75 years with biopsy-confirmed MASH at F2 or F3 stage fibrosis may participate. Participants must have at least two components of metabolic syndrome and meet specific health criteria.
  • Study details: Participants will receive a subcutaneous injection of either the investigational medication or a placebo every four weeks. The placebo is an inactive substance that looks like the investigational medication but does not contain any medicine.
  • Study timelines: The study will last 52 months.
Updated on 07 Jul 2026. Study ID: GI-GSK-ZENITH-1, 30759
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only