Phase 3, randomised, 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)
Metabolic dysfunction-associated steatohepatitis (MASH) is a condition where excess fat in the liver leads to swelling, inflammation, and tissue scarring (fibrosis). If left untreated, this scarring can damage how the liver works over time. This Phase 3 study, called ZENITH-1, is looking at whether a new medicine called efimosfermin alfa can help heal the liver. Participants are randomly put into one of three groups to receive either a lower dose, a higher dose, or a dummy injection (placebo) once every four weeks for four years. The study involves regular health checks and tests at the hospital to monitor liver health and general safety. The trial is open to adults aged 18 to 75 who have confirmed liver scarring at stage F2 or F3. Taking part lasts about 52 months in total, including screening and follow-up safety checks.
At a glance
What is this study about?
MASH is an advanced type of fatty liver disease. It happens when fat builds up inside liver cells, causing the organ to become swollen and inflamed. Over months and years, this ongoing inflammation can lead to fibrous scar tissue forming inside the liver. In this trial, researchers are focusing on people with moderate to advanced scarring, known as stages F2 and F3, to try to prevent the damage from becoming more severe.
Efimosfermin alfa is an experimental medicine designed to copy natural signals in the body that regulate how the liver handles fats and sugars. Researchers hope it will calm down liver inflammation, clear out excess fat, and perhaps even reverse some of the existing scar tissue. Because this is a Phase 3 trial, it is one of the final stages of testing to see if the medicine works well and is safe for wider use.
Finding an effective treatment for MASH is vital because there are currently very few approved medicines available for this condition. By joining this trial, participants help doctors learn whether this new monthly injection can slow or stop liver damage and lower the chance of long-term liver complications.
Key takeaways
- Tests a new monthly injection (efimosfermin alfa) to treat liver swelling and scarring caused by MASH.
- Open to adults aged 18 to 75 with biopsy-confirmed stage F2 or F3 liver fibrosis.
- Participants are randomly assigned to receive either the active medicine or a dummy injection (placebo).
- Treatment lasts for 48 months with regular health checks and liver scans.
- Participation is entirely voluntary and you can leave the study at any time.
Who may be eligible?
This study is designed for adults aged between 18 and 75 years old who have been diagnosed with MASH and have moderate to advanced liver scarring (fibrosis stage F2 or F3). This scarring must be confirmed by a small sample of liver tissue (a biopsy) examined by study specialists.
Because MASH is closely tied to overall metabolism, participants also need to have at least two common metabolic health factors. These can include carrying extra weight around the waist, high blood pressure, high blood fats (triglycerides), low levels of 'good' HDL cholesterol, or raised fasting blood sugar levels.
To ensure results are clear and reliable, your body weight must have stayed fairly steady over the previous six months. You may not be able to take part if you have more severe, end-stage liver scarring (cirrhosis), other forms of liver disease, or if you are currently taking other experimental medicines.
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 between 18 and 75 years of age.
- I have been diagnosed with MASH (fatty liver inflammation) with stage F2 or F3 scarring.
- I have had, or am willing to have, a liver biopsy to confirm the stage of my liver disease.
- I have at least two metabolic factors (such as high blood pressure, raised blood sugar, or carrying extra weight).
- My body weight has been reasonably steady for the past six months.
What does participation involve?
Taking part in the study lasts for about 52 months (roughly four and a half years). This includes up to three months of health screening before starting, 48 months of treatment, and a final safety check a few weeks after the last dose. You will be placed at random into one of three groups: you will receive either a 225 mg dose, a 300 mg dose of efimosfermin alfa, or a placebo injection that contains no active medicine. Neither you nor the trial doctor will know which group you are in.
The medicine is given as a quick injection under the skin (subcutaneous) once every four weeks. You will need to attend regular clinic appointments at the hospital, such as King's College Hospital in London. During these visits, the study team will take blood tests, monitor your blood pressure and weight, perform liver scans (such as MRI or ultrasound elastography), and check on any side effects. You may also need repeat liver biopsies during the study so doctors can see if the scarring has improved.
Potential risks and benefits
Locations (1)
- -Approximate-, England
Common questions
What is a placebo and why is it used?
A placebo looks just like the real medicine but contains no active ingredient. It acts as a baseline so researchers can be confident that any improvements or side effects are truly caused by the study drug.
Will I have to pay to take part?
No, all study medicines, specialist tests, scans, and clinic visits are provided free of charge. In many cases, travel expenses to and from the clinic are also reimbursed.
How is the study medicine given?
The medicine is given as a small injection under the skin once every four weeks, similar to how insulin or some allergy injections are given.
Can I keep taking my usual regular prescriptions?
Most routine medicines for conditions like blood pressure or cholesterol are allowed, but the study team will carefully review all your current tablets to make sure they are safe to use alongside the study drug.
What happens if I change my mind during the study?
You are completely free to leave the trial at any point, for any reason. Your normal relationship with your doctors and your usual medical treatment will continue as normal.
How to find out more
Sona Drezikova
Always speak to your GP or specialist before deciding to take part in a study.
Interested in taking part?
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