AuthorisedTherapeutic confirmatory (Phase III)Interventional

A Phase 3, two-part, double-blind, randomized, placebo-controlled study to investigate the safety and efficacy of efimosfermin alfa injection in adult participants with compensated cirrhosis (stage F4 fibrosis) due to metabolic dysfunction-associated steatohepatitis (NEBULA-2)

Metabolic dysfunction-associated steatohepatitis (MASH) is a condition where fat build-up causes inflammation and damage in the liver. Over time, this damage can lead to severe scarring known as cirrhosis. While the liver is heavily scarred, it may still be working well enough to carry out its normal jobs (known as compensated cirrhosis). This Phase 3 study is testing an investigational medicine called efimosfermin alfa. Participants are randomly chosen to receive either this new medicine or a dummy treatment (placebo) given by injection. Neither the participants nor the study doctors will know who gets which treatment during the study. Researchers want to find out whether efimosfermin alfa can help reverse or heal the scarring by at least one stage without letting the liver disease get worse, and to check how safe it is to use.

At a glance

Status

Authorised

Phase

Therapeutic confirmatory (Phase III)

Sponsor

Glaxosmithkline Research & Development Limited

Enrolment target

Start

13 Oct 2026

Metabolic dysfunction-associated steatohepatitis

What is this study about?

MASH is a serious type of fatty liver disease linked to metabolic health, such as how the body handles sugars and fats. When fat builds up in the liver cells, it can cause swelling and long-term inflammation. Over many years, this ongoing inflammation leads to tough scar tissue forming throughout the liver. Stage 4 scarring is called cirrhosis. In 'compensated' cirrhosis, the scarring is widespread, but the liver is still managing to function without failing.

Currently, there are very few approved treatments that can reverse severe liver scarring. This clinical study, called NEBULA-2, is exploring whether a new injectable medicine called efimosfermin alfa can help heal damaged liver tissue. Scientists hope the medicine can calm inflammation and help the liver break down some of the tough scar tissue.

Because this is a Phase 3 study, it is in the final stages of clinical testing before a medicine can be approved for general use. Researchers will compare the study medicine against an inactive dummy injection (a placebo). By comparing the two groups, the trial team can clearly see whether any health improvements or side effects are truly caused by efimosfermin alfa.

Taking part helps medical experts discover whether this treatment can safely improve liver health. If the trial is successful, it could provide a much-needed treatment option for people living with advanced liver scarring.

Key takeaways

Tests a new injection (efimosfermin alfa) for people with severe liver scarring from MASH.
Aims to find out if the drug can reverse liver scarring and protect liver function.
Compares the study drug against an inactive dummy injection (placebo).
Open to adults aged 18 and over with compensated (stable) cirrhosis.
Involves regular hospital check-ups, non-invasive liver scans, and blood tests.
Participation is completely voluntary and you can withdraw at any time.

Who may be eligible?

This trial is open to men and women aged 18 and older who have been diagnosed with MASH and have compensated cirrhosis (stage 4 fibrosis). Having compensated cirrhosis means that although your liver has significant scarring, it is still working well enough to support your body's basic needs.

You will need to have medical tests to confirm the stage of your liver scarring and to ensure your liver has not become 'decompensated' (meaning it has started to fail). The study team will review your medical records, perform scans, and check blood samples to make sure it is safe for you to take part.

People with certain other liver conditions (such as hepatitis B or C), heavy alcohol use, or uncontrolled serious health problems may not be able to join. The study doctor will discuss your full medical history with you to see if the study is a good match.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged 18 or older.
I have been diagnosed with fatty liver disease or MASH.
I have been told by a doctor that I have liver scarring or compensated cirrhosis.
My liver is currently working stably without signs of liver failure.
I am willing to receive regular injections and attend hospital check-ups.

Answer every question to see your result.

What does participation involve?

If you join this trial, you will attend regular appointments at a specialist hospital clinic. Before starting, you will go through a screening period to check your overall health and confirm your liver stage. If you are eligible, you will be randomly assigned by a computer to receive either efimosfermin alfa or a placebo injection.

You will receive the study medicine as an injection just under the skin. Throughout the trial, you will have regular clinic visits so the team can monitor your health closely. These visits will include blood tests, physical examinations, and specialised non-invasive liver scans (such as a FibroScan) to measure liver stiffness. You will also be asked about how you are feeling and any side effects you might notice. The trial takes place over several months to a couple of years, and the study team will guide you through each step.

Potential risks and benefits

A potential benefit of joining is that the study medicine might help improve your liver scarring and liver health, although this cannot be guaranteed. You will also receive comprehensive, regular health check-ups from liver specialists. However, there are risks to consider. You could experience side effects from the study injection, such as mild reactions where the needle goes in, stomach upsets, or other unexpected symptoms. There is also a 50% chance that you will receive the placebo, which contains no active medicine. Joining the trial is entirely voluntary, and you are free to leave at any time without it affecting your usual NHS medical care.

Locations (10)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

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Unverified
Netherlands
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Unverified
Germany
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Unverified
Austria
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Unverified
France
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Unverified
Spain
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Unverified
Italy
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Unverified
Bulgaria
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Unverified
Poland
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Unverified
Belgium
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Unverified
Greece

Common questions

What is MASH?

MASH stands for metabolic dysfunction-associated steatohepatitis. It is an advanced form of fatty liver disease where fat build-up leads to swelling, inflammation, and scarring in the liver.

What does compensated cirrhosis mean?

Cirrhosis means the liver has severe scarring. 'Compensated' means the liver is still coping and performing its vital daily functions without major complications like fluid swelling or jaundice.

What is a placebo?

A placebo is a dummy treatment designed to look just like the real medicine but containing no active ingredient. It helps doctors measure the true effects of the study drug.

Will taking part cost me anything?

No, the study medication, clinic visits, and all trial-related tests are provided free of charge. Travel expenses to and from the hospital are usually reimbursed.

Can I stop taking part if I change my mind?

Yes, you can leave the study at any point without giving a reason. Your standard medical treatment and relationship with your doctors will not be affected.