Efinopegdutide for Fatty Liver Disease

Recruiting in Palo Alto (17 mi)

+61 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Merck Sharp & Dohme LLC

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Researchers are looking for ways to treat a type of liver disease caused by elevated liver fat, called metabolic dysfunction-associated steatohepatitis (MASH). MASH was formerly called non-alcoholic steatohepatitis (NASH). Researchers want to learn if a study medicine called efinopegdutide can treat MASH.The goals of this study are to learn: * If efinopegdutide can lower the amount of fat, inflammation, and scarring (fibrosis) in the liver * About the safety of efinopegdutide and how well people tolerate it

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.

What data supports the effectiveness of the drug Efinopegdutide for treating fatty liver disease?

Research shows that drugs similar to Efinopegdutide, which target GLP-1 and glucagon receptors, can reduce liver fat and improve liver health in patients with non-alcoholic fatty liver disease. Studies on similar drugs like semaglutide and cotadutide have shown promising results in reducing liver fat and improving liver function. ^{1 2 3 4 5}

Is efinopegdutide safe for humans?

Efinopegdutide has been studied for its safety in patients with non-alcoholic fatty liver disease, and the findings suggest it is generally safe for human use. Safety and tolerability findings were comparable to those of similar treatments, indicating no major safety concerns. ^{1 4 5 6 7}

What makes the drug Efinopegdutide unique for treating fatty liver disease?

Efinopegdutide is unique because it targets both the GLP-1 and glucagon receptors, which may help reduce liver fat more effectively than treatments that only target the GLP-1 receptor, like semaglutide. ^{1 4 5 7 8}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Efinopegdutide (Peptide)

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.

Participant Groups

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

Findings from Research

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]

References

1. Netherlands 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. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of glucagon-like peptide-1 on glucagon secretion in patients with non-alcoholic fatty liver disease. [2018]

3. Egypt 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. [2021]

4. Switzerland 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. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

GLP-1 analogue prevents NAFLD in ApoE KO mice with diet and Acrp30 knockdown by inhibiting c-JNK. [2015]

8. Germany 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. [2021]