Safety and efficacy of efimosfermin alfa in adults with biopsy-confirmed F2 or F3 stage Metabolic Dysfunction-Associated Steatohepatitis (MASH)

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What is this study about?

The study focuses on adults with biopsy‑confirmed Metabolic Dysfunction-Associated Steatohepatitis (MASH) that is classified as stage F2 or F3, indicating moderate to advanced liver scarring. Participants receive a subcutaneous injection of the investigational drug efimosfermin alfa or a matching placebo for up to one year, with the option to continue treatment for several years to observe longer‑term effects.

The purpose of the study is to determine whether efimosfermin alfa can improve liver health compared with placebo by reducing the amount of scarring and the presence of fatty inflammation. After random assignment, participants attend regular clinic visits where a small tissue sample (biopsy) may be taken to examine liver cells under a microscope, and non‑invasive imaging tests such as a magnetic resonance imaging (MRI) scan are used to measure liver stiffness and fat content. Blood tests that include enzymes like alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as a diabetes‑related measure called hemoglobin A1c (HbA1c) are performed to track changes in liver function and overall metabolism throughout the 52‑week treatment period and during extended follow‑up.

1 randomization and first injection

after enrollment, the participant is randomly assigned to receive either efimosfermin alfa or a matching placebo.

the first dose is given as a subcutaneous injection (injection under the skin) according to the study schedule.

2 regular injection visits

the participant returns to the clinic at each scheduled visit to receive the next subcutaneous injection of the assigned study medication.

the exact dose, frequency, and interval are defined by the trial protocol; specific numbers are not provided in the source material.

3 routine safety and health monitoring

at each visit, the participant undergoes safety assessments, which may include blood tests, physical examinations, and questionnaires about symptoms.

these assessments help determine whether any adverse events occur during the treatment period.

4 week 52 evaluation

after 52 weeks of continuous treatment, the participant undergoes a detailed evaluation to assess changes in liver condition.

the primary goals are to determine whether there is improvement in fibrosis (scarring) and resolution of steatohepatitis (liver inflammation) without worsening of disease.

5 month 48 (up to 48 months) evaluation

the participant may continue treatment for up to 48 months, after which a long‑term assessment is performed.

this assessment examines the time to a composite liver‑related clinical outcome and further evaluates changes in liver health.

6 study completion and final analysis

upon completion of the designated treatment period, the participant stops receiving study medication.

all collected data are analyzed to determine the overall safety and efficacy of efimosfermin alfa compared with placebo.

Who Can Join the Study?

You must be able to understand the study information and sign a written informed consent form before any study procedures begin. (Informed consent means you agree to take part after the doctors explain what will happen.)
You need to be between 18 and 75 years old when you join the study.
You must have at least two of the five health problems that make up metabolic syndrome (such as high blood pressure, high blood sugar, excess belly fat, high triglycerides, or low “good” cholesterol) as defined by the American Heart Association.
You must have a confirmed diagnosis of Metabolic Dysfunction-Associated Steatohepatitis (MASH) from a liver tissue sample (liver biopsy) that shows stage F2 or F3 fibrosis (moderate to advanced scarring) and a NAS score of 4 or higher, as reviewed by a specialized doctor (central pathologist).

Who Cannot Join the Study?

You cannot have a percutaneous liver biopsy (a needle procedure to take a small piece of liver tissue) or you are not eligible for it.
Your glycated hemoglobin (A1C) level is 9% or higher, indicating poor blood‑sugar control.
Your Model for End‑Stage Liver Disease (MELD) score is 12 or higher, unless the high score is due to a harmless condition like Gilbert’s syndrome.
Your phosphatidyl ethanol (PEth) test (a blood test that shows recent alcohol use) is 80 ng/mL or higher.
You have an infection with HIV, Hepatitis B (detectable surface antigen), or Hepatitis C.
You have another long‑term liver disease (such as alcoholic liver disease), signs of portal hypertension (high pressure in the liver’s blood vessels), any viral hepatitis, scarring of the liver (cirrhosis) seen on a biopsy, or serious liver complications like fluid buildup in the abdomen (ascites), bleeding from veins in the esophagus or stomach (gastroesophageal varices), kidney problems caused by liver disease (hepatorenal syndrome), or confusion due to liver failure (hepatic encephalopathy) before screening.
You have been drinking heavily for three months or more within the past year.
Your liver enzymes ALT or AST are five times higher than the normal range.
Your total bilirubin level (a substance that can make the skin yellow) is 1.3 mg/dL or higher, unless you have Gilbert’s syndrome with only a mild isolated rise and the direct portion is low.
Your blood albumin (a protein that shows how well the liver makes proteins) is 3.5 g/dL or less.
Your INR (a test that measures blood clotting) is 1.3 or higher, unless it is because you are taking blood‑thinning medication.
Your alkaline phosphatase (ALP) level (an enzyme that can be high with liver or bone problems) is twice the normal level.
Your platelet count (cells that help blood clot) is less than 140,000 per microliter.
Your creatinine level (a waste product that shows kidney function) is 1.5 mg/dL or higher, or your kidney clearance is 60 mL per minute or less.
Your alpha‑fetoprotein level (a blood protein that can be high in liver disease) is 20 ng/mL or higher.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Medical University Of Vienna	Vienna	Austria
Center For Pediatric And Adolescent Medicine Of The Johannes Gutenberg University Mainz	Mainz	Germany
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany
Multiprofile Hospital For Active Treatment Hadji Dimitar OOD	Sliven	Bulgaria
Medical University Of Graz	Graz	Austria
Universitaet Leipzig	Leipzig	Germany
Medizinische Universitaet Innsbruck	Innsbruck	Austria
Acibadem City Clinic Diagnostic And Consultation Center Tokuda EAD	Sofia	Bulgaria
Université Libre de Bruxelles – Hôpital Erasme	Brussels	Belgium

Other Sites

Site Name	City	Country
University Multiprofile Hospital For Active Treatment Saint Georgi EAD	Plovdiv	Bulgaria
University Multiprofile Hospital For Active Treatment And Emergency Medicine N I Pirogov	Sofia	Bulgaria
Hippokration Hospital	Athens	Greece
Landeskrankenanstalten-Betriebsgesellschaft Kabeg	Klagenfurt am Wörthersee	Austria
Evangelismos S.A.	Athens	Greece
Diagnostic Consultative Centre Ascendent OOD	Sofia	Bulgaria
University General Hospital Of Thessaloniki Ahepa	Thessaloniki	Greece
Medical Center Hera EOOD	Sofia	Bulgaria
Medical Centre Futuremeds EOOD	Plovdiv	Bulgaria
Diagnostic-consultative center “Aleksandrovska” EOOD	Sofia	Bulgaria
Universitätsklinikum des Saarlandes – Homburg/Saar, Klinik für Urologie und Kinderurologie	Homburg	Germany
Multispecialty hospital for active treatment Sveta Sofia EOOD	Sofia	Bulgaria
Virgen del Rocío University Hospital	Sevilla	Spain
Charite Universitaetsmedizin Berlin KöR	Berlin	Germany
Hospital Universitario De Leon	Leon	Spain
Hospital General Universitario De Valencia	Valencia	Spain
Klinik Hietzing	Vienna	Austria
Epimed Gesellschaft fuer epidemiologische und klinische Forschung in der Medizin mbH	Berlin	Germany
Hospital General De Tomelloso	Tomelloso	Spain
Centre hospitalier universitaire de Liege	Liege	Belgium
Universitair Ziekenhuis Gent	Gent	Belgium
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Az Maria Middelares Gent	Gent	Belgium
University General Hospital Of Heraklion	Heraklion	Greece
Hospital Quironsalud Barcelona	Barcelona	Spain
Policlinica Gipuzkoa S.A.	Donostia / San Sebastian	Spain
Hospital Clinico Universitario De Valladolid	Valladolid	Spain
Eugastro GmbH	Leipzig	Germany
Micancer Center S.L.P.	Barcelona	Spain
Multiprofile Hospital For Active Treatment-Uni Hospital Ltd.	Panagyurishte	Bulgaria
Bernhoven B.V.	Uden	The Netherlands
Multiprofile Hospital For Active Treatment St. Ivan Rilski Gorna Oriahovitsa EOOD	Gorna Oryahovitsa	Bulgaria
MBAL Trakia EOOD	Stara Zagora	Bulgaria
Cyjlglvig Uuqzjklafnjuwv Sbjvbewuy	Woluwe-Saint-Lambert	Belgium
Ueyxnwwrqr Hdbkcajr Llyhpqkl	Sofia	Bulgaria
Ljmad Gjlhgec Hjbhhcot Op Alxvma	Athens	Greece
Hqzwtrbj Vfyd dpcuwgqe	Barcelona	Spain
Hfdspiex Uenbsujqmgmsq df A Cdnzqn	A Coruna Galicia	Spain
Atlxuiwle Udm	Amsterdam	The Netherlands
Egilhzv Uvtglwxlzbsj Mujxivy Cglicvt Rxuhqfeuj (gwbuult Mym	Rotterdam	The Netherlands
Ueyezfgzwrjjmvmdgvvif Mmuzgnpr Akv	Munster	Germany
Mvjgkpia Mhpeaka Abucqwt	Pleven	Bulgaria
Hhhjerro Dr Ld Syqcw Cqlf I Sxxx Pti	Barcelona	Spain
Uafsmphttb Ov Abfrksi	Edegem	Belgium
Ugjjsxlqop Mvmvazh Chxufg Hebtxndgnsrscvkvz	Hamburg	Germany
Hvrcklns Ukeemohlgholz Da Lj Pfpzcbrx	Madrid	Spain
Hccefklp Uqoicibexhvma Mwzzdyj Dd Vvklxhsiov	Santander	Spain

Trial status

Country	Status	Recruitment Start
Austria	Not yet recruiting	06.07.2026
Belgium	Not yet recruiting	06.07.2026
Bulgaria	Not yet recruiting	06.07.2026
Germany	Not yet recruiting	06.07.2026
Greece	Not yet recruiting	06.07.2026
Spain	Not yet recruiting	06.07.2026
The Netherlands	Not yet recruiting	06.07.2026

Trial locations

Efimosfermin Alfa is a medication being tested to see if it can help people with a liver condition called metabolic dysfunction‑associated steatohepatitis (MASH). In the study, it is given as a powder that is mixed with liquid and injected under the skin. Researchers are looking at whether the drug can improve the liver’s appearance under a microscope and reduce scarring (fibrosis) after one year of treatment, and whether it can lower the risk of serious liver‑related problems over several years.

Metabolic Dysfunction-Associated Steatohepatitis (MASH) – It is a liver condition where excess fat accumulates in the liver together with inflammation caused by metabolic problems such as obesity or diabetes. The inflammation damages liver cells and triggers the formation of scar tissue, known as fibrosis. As more scar tissue builds up, the liver becomes less able to perform its normal functions. The disease can advance from mild stages with limited scarring to more severe stages with extensive fibrosis. This progression occurs over months to years.

Trial ID:

2025-523675-39-00

Protocol code:

301160

NCT ID:

NCT07221227

Trial Phase:

Therapeutic confirmatory (Phase III)

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Safety and efficacy of efimosfermin alfa in adults with biopsy-confirmed F2 or F3 stage Metabolic Dysfunction-Associated Steatohepatitis (MASH)

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?