A randomized, double-blind, placebo-controlled, multicenter, phase IIb clinical study to evaluate the efficacy and safety of Efinopegdutid (MK-6024) in adults with nonalcoholic steatohepatitis (NASH) who have not yet developed cirrhosis.

Zusammenfassung der Studie

This study evaluates the efficacy and safety of different doses of Efinopegdutid (MK-6024) compared to a placebo and Semaglutide. A placebo looks visually like the drug under investigation but contains no active ingredient. The main objectives of this study are to examine the efficacy of Efinopegdutid compared to placebo using liver tissue examinations and tests. This aims to observe the resolution of NASH and/or the improvement of fibrosis. Additionally, the safety and tolerability of Efinopegdutid will be assessed by observing the side effects occurring during the study. Participants in this study will be adults with nonalcoholic steatohepatitis (NASH) who have not yet developed cirrhosis. The diagnosis of NASH must have been histologically confirmed by a liver biopsy. Efinopegdutid resembles a protein produced in the intestine after eating and binds to two different receptors: GLP-1 and GCG. This binding could have positive effects for NASH patients on insulin secretion, hunger sensation, energy expenditure, and fat metabolism. Therefore, Efinopegdutid could represent an effective therapy for NASH. Semaglutide is used in the study as a comparator drug. Semaglutide is approved in some countries, including Switzerland, for the treatment of conditions often associated with NASH, including weight and blood sugar control. However, it is not approved for the treatment of NASH. Efinopegdutid, Semaglutide, and the placebo will be administered as injections under the skin. Approximately 300 patients aged 18 to 80 years are expected to participate in this study worldwide. The study will be conducted over a period of approximately 70 weeks, with 14 planned clinical visits.

(BASEC)

Untersuchte Intervention

After a maximum 10-week screening phase, each eligible participant will be randomly assigned to treatment with either Efinopegdutid, placebo, or Semaglutide. The treatment duration may last up to 52 weeks. A follow-up will occur 9 weeks after the last dose of the study medication.

After careful eligibility screening, collection of medical history, and detailed information, the participant will be included in the study and randomly assigned in a 1:1:1:1:1 ratio to one of the following groups:

• Groups 1, 2, and 3: Receive different doses of Efinopegdutid

• Group 4: Receives Semaglutide

• Group 5: Receives the placebo

For groups 1, 2, 3, and 5: Neither the study doctor nor the participants know which group they are assigned to and thus whether they are taking Efinopegdutid or placebo (these groups are referred to as "double-blind").

For group 4: The study doctor and the participants know which group they are assigned to and thus that Semaglutide is being administered (this group is referred to as "open-label").

Efinopegdutid, Semaglutide, and the placebo will each be administered weekly as injections under the skin. The study staff will train participants on how to inject the study medications into an abdominal fold, thigh, or upper arm. They will also show how to keep a diary to document medication intake. In the first weeks of treatment, the dose of the medication will be gradually increased to the assigned stable dose.

As part of study visits, various measures and examinations may be performed, e.g.: electrocardiogram (ECG), liver examination (VCTE: vibration-controlled transient elastography), bone imaging scans (DXA scan: dual-energy X-ray absorptiometry), liver biopsy, assessment of general health status, discussions with medical staff. The study team may also contact participants between visits and after the completion of the study medication intake to check on their health status.

Approximately 9 weeks after the last dose of the study medication, patients will visit the study center for a follow-up.

(BASEC)

Untersuchte Krankheit(en)

Nonalcoholic fatty liver disease (NAFLD) is associated with increased fat accumulation in the liver and affects about 25% of the adult global population. Nonalcoholic steatohepatitis (NASH) is the more severe form of NAFLD and is characterized by fat accumulation in the liver, chronic inflammation, liver cell damage, and scarring (fibrosis). Symptoms of NASH are often nonspecific and can therefore be easily overlooked. In NASH, liver values may be elevated, which can indicate liver damage. In advanced stages of the disease (approximately 20% of the NASH population), cirrhosis may occur, leading to complications such as liver failure and liver cancer. The exact causes are not yet fully understood, but various factors are believed to play a role. Possible risk factors include overweight, an unhealthy diet, insulin resistance (a disorder in glucose metabolism often associated with diabetes), and genetic predisposition. Currently, there are no approved medications for the treatment of NASH. Current treatments primarily aim to learn healthier lifestyle habits and reduce weight.

(BASEC)

Sponsor

Merck Sharp & Dohme LLC, USA («MSD») MSD Merck Sharp & Dohme AG, Luzern

(BASEC)

Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Ethikkommission Zürich

(BASEC)

Datum der Bewilligung durch die Ethikkommission

19.09.2023

(BASEC)

Ergebnisse der Studie