Efinopegdutide for Fatty Liver Disease

Not currently recruiting at 74 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Hepatitis, Type 1 diabetes, Heart problems, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, efinopegdutide, to determine its effectiveness in treating metabolic dysfunction-associated steatohepatitis (MASH), a liver disease caused by excess fat. Researchers aim to see if this medicine can reduce liver fat, inflammation, and scarring while ensuring it is safe and well-tolerated. Participants will receive weekly injections over 28 weeks, either of efinopegdutide or a placebo (a look-alike with no active medicine). Individuals with MASH-related liver cirrhosis and possibly controlled type 2 diabetes might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that efinopegdutide is likely to be safe for humans?

Research has shown that efinopegdutide has been tested in people with liver problems similar to MASH. In these studies, efinopegdutide was generally well-tolerated. For example, one study found that participants who received weekly doses experienced a greater reduction in liver fat compared to another treatment. This suggests that efinopegdutide might be effective and safe.

Most participants in these trials managed the treatment without major issues. However, like any treatment, some side effects can occur. It is important to note that this trial is in the middle stage of testing, meaning some safety information is available, but more data is still being collected. Always consult a healthcare professional before deciding to participate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MASH?

Efinopegdutide is unique because it uses a novel approach to target fatty liver disease. Unlike standard treatments that often focus on lifestyle changes or medications like vitamin E and pioglitazone, efinopegdutide is a peptide-based drug that acts on specific receptors to potentially improve liver health more directly. Researchers are excited about its potential to offer a new mechanism of action, as it is administered via a once-weekly subcutaneous injection, which could improve patient compliance and outcomes compared to daily oral medications.

What evidence suggests that efinopegdutide might be an effective treatment for MASH?

Research has shown that efinopegdutide, which participants in this trial may receive, may help reduce liver fat in people with non-alcoholic fatty liver disease (NAFLD). In one study, patients who took efinopegdutide experienced a greater decrease in liver fat than those who took semaglutide, another treatment option. Efinopegdutide targets two specific areas in the body that help control metabolism. This action might help lower liver fat, reduce inflammation, and prevent scarring. These results suggest that efinopegdutide could be effective for treating metabolic dysfunction-associated steatohepatitis (MASH), previously known as NASH. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for individuals with compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH), previously known as NASH. Participants may also have type 2 diabetes that's managed by diet or medication, or they might not have diabetes at all.

Inclusion Criteria

I either don't have type 2 diabetes or it's controlled by diet or medication.

I have a stable form of liver cirrhosis due to fatty liver disease.

Exclusion Criteria

I haven't had major heart problems or strokes in the last 6 months.

I had weight loss surgery less than 5 years ago.

I have had pancreatitis before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive efinopegdutide or placebo as a subcutaneous injection once a week, with dose escalation for efinopegdutide over the first three months, for a total of 28 weeks

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Efinopegdutide

Trial Overview The study is testing efinopegdutide, a potential treatment for MASH. It aims to see if this medicine can reduce liver fat, inflammation, and scarring. The trial will compare the effects of efinopegdutide against a placebo.

How Is the Trial Designed?

Group I: Efinopegdutide Experimental Treatment 1 Intervention

Participants will start efinopegdutide once a week at the lowest dose level. Then, the dose level will go up every month for three months until they are getting the highest dose level. Efinopegdutide is given as an injection under the skin (subcutaneous injection) for 28 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo once a week. A placebo looks like the study medicine but has no study medicine in it. Using a placebo helps researchers better understand the effects of a study medicine. Placebo is given as an injection under the skin (subcutaneous injection) for 28 weeks.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase IIa study involving 145 participants with non-alcoholic fatty liver disease (NAFLD), efinopegdutide (10 mg weekly) resulted in a significantly greater reduction in liver fat content (LFC) compared to semaglutide (1 mg weekly), with reductions of 72.7% and 42.3% respectively after 24 weeks (p < 0.001).

Both treatments led to weight loss, with efinopegdutide showing an 8.5% reduction compared to 7.1% for semaglutide, although efinopegdutide was associated with slightly higher gastrointestinal adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. Romero-Gómez, M., Lawitz, E., Shankar, RR., et al.[2023]

In a phase 2a trial involving men and women with overweight or obesity and type 2 diabetes, cotadutide significantly reduced liver glycogen and fat compared to both placebo and liraglutide, indicating its efficacy in improving liver health.

The safety and tolerability of cotadutide were found to be comparable to previous studies, suggesting it is a safe option for treating conditions like non-alcoholic steatohepatitis and type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes. Parker, VER., Robertson, D., Erazo-Tapia, E., et al.[2023]

A systematic review of 11 randomized controlled trials involving 936 middle-aged individuals found that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduced liver fat content and serum liver enzyme levels in patients with nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH) over a median treatment duration of 26 weeks.

GLP-1 RAs, particularly liraglutide and semaglutide, also showed greater histological resolution of NASH without worsening liver fibrosis, indicating their potential as effective treatments for these liver conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. Mantovani, A., Petracca, G., Beatrice, G., et al.[2021]

Liraglutide effectively prevents the development of insulin resistance and non-alcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet, demonstrating its potential as a protective treatment against these conditions.

The mechanism of action involves the inhibition of the MKK4/JNK signaling pathway, leading to reduced inflammation and improved insulin sensitivity, as indicated by decreased levels of proinflammatory cytokines and lipogenesis-related genes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 analogue prevents NAFLD in ApoE KO mice with diet and Acrp30 knockdown by inhibiting c-JNK. Zhang, L., Yang, M., Ren, H., et al.[2015]

Cotadutide, a GLP-1R/GcgR agonist, effectively reduces body weight, food intake, and improves glucose control primarily through GLP-1 signaling, while its beneficial effects on liver health are mediated by Gcg signaling, as shown in preclinical studies.

In comparison to other treatments like Liraglutide and Obeticholic acid, Cotadutide demonstrated a greater ability to alleviate liver fibrosis in mouse models of non-alcoholic steatohepatitis (NASH), highlighting its potential as a promising therapeutic option for liver diseases associated with obesity and type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resolution of NASH and hepatic fibrosis by the GLP-1R/GcgR dual-agonist Cotadutide via modulating mitochondrial function and lipogenesis. Boland, ML., Laker, RC., Mather, K., et al.[2021]

Liraglutide, a GLP-1 analogue, has shown safety and efficacy in treating two adolescent females with type II diabetes and biopsy-proven nonalcoholic steatohepatitis (NASH), leading to weight loss and improved liver enzymes.

This case series suggests that liraglutide could be a beneficial treatment option for pediatric patients with obesity, NAFLD, and T2DM, especially when lifestyle interventions are ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide with Lifestyle Intervention in Adolescents with Overweight/Obesity, Nonalcoholic Fatty Liver Disease, and Type II Diabetes Mellitus. Kohut, T., Panganiban, J.[2023]

In a study involving 10 non-diabetic patients with non-alcoholic fatty liver disease (NAFLD) and 10 matched controls, GLP-1 infusion effectively suppressed glucagon levels in both groups, indicating that the glucagon-suppressive effect of GLP-1 is preserved in NAFLD patients.

Despite the presence of fasting hyperglucagonaemia in NAFLD patients, GLP-1 did not affect endogenous glucose production, suggesting that while GLP-1 enhances insulin secretion in these patients, it does not alter glucose output from the liver.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of glucagon-like peptide-1 on glucagon secretion in patients with non-alcoholic fatty liver disease. Junker, AE., Gluud, LL., van Hall, G., et al.[2018]

GLP-1 receptor agonists (GLP-1RA) significantly reduce liver enzymes such as alanine transaminase (ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) in patients with nonalcoholic fatty liver disease (NAFLD), based on a meta-analysis of 12 studies involving 677 subjects.

However, GLP-1RA treatment does not significantly affect the lipid profile, including triglycerides, total cholesterol, high-density lipoprotein (HDL), or low-density lipoprotein (LDL), indicating that while they help with liver health, they do not improve lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 Receptor Agonist Effects on Lipid and Liver Profiles in Patients with Nonalcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis. Rezaei, S., Tabrizi, R., Nowrouzi-Sohrabi, P., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37355043/

A phase IIa active-comparator-controlled study to evaluate ... In patients with NAFLD, treatment with efinopegdutide 10 mg weekly led to a significantly greater reduction in LFC than semaglutide 1 mg weekly.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05877547

NCT05877547 | A Clinical Study of Efinopegdutide in ... The purpose of this study is to learn how well efinopegdutide works compared to placebo in people who have non-alcoholic steatohepatitis (NASH).

3. merck.com merck.com/news/merck-to-present-data-for-efinopegdutide-mk-6024-an-investigational-glp-1-glucagon-receptor-co-agonist-in-patients-with-nonalcoholic-fatty-liver-disease-nafld-at-easl-2023/

Merck to Present Data for Efinopegdutide (MK-6024), an ... Data to be shared include results from the Phase 2a clinical trial evaluating efinopegdutide in adult patients with nonalcoholic fatty liver disease (NAFLD).

4. adisinsight.springer.com adisinsight.springer.com/drugs/800040692

Efinopegdutide - Hanmi Pharmaceutical - AdisInsight Efinopegdutide, a glucagon/glucagon-like peptide-1 (GLP-1) dual agonist is being developed by Hanmi Pharmaceutical in collaboration with Merck & Co for the.

5. swolverine.com swolverine.com/blogs/blog/efinopegdutide-mk-6024-dual-glp-1-glucagon-peptide-for-metabolic-liver-disease?srsltid=AfmBOop_B2TfuPj2svJO-oArh5Gk-PCnRzKjS8YkNeSiLHlsKZ38td8w

Efinopegdutide (MK‑6024): Dual GLP‑1/Glucagon Peptide ... Efinopegdutide (MK‑6024) is a dual GLP‑1/glucagon receptor agonist under investigation for treating metabolic-associated fatty liver disease ( ...

6. swolverine.com swolverine.com/blogs/blog/efinopegdutide-mk-6024-dual-glp-1-glucagon-peptide-for-metabolic-liver-disease?srsltid=AfmBOoo4d8nJTy9Of52gZxwkPZlVhfvc4Podwg2C2rVCdJi_MMyd8Bhy

Efinopegdutide (MK‑6024): Dual GLP‑1/Glucagon Peptide ... Efinopegdutide (MK‑6024) is a dual GLP‑1/glucagon receptor agonist under investigation for treating metabolic-associated fatty liver disease ( ...