Efinopegdutide for Nonalcoholic Steatohepatitis (NASH)

Not currently recruiting at 208 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antihyperglycemic agents

Disqualifiers: Liver disease, Cirrhosis, Pancreatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called efinopegdutide for individuals with non-alcoholic steatohepatitis (NASH), a liver condition that causes inflammation and damage. Researchers aim to compare the effectiveness of efinopegdutide, a potential new drug, against a placebo and another treatment, semaglutide. The primary goal is to determine if efinopegdutide can help reduce signs of NASH without worsening liver scarring. The trial seeks participants confirmed to have NASH and no other liver diseases. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have Type 2 diabetes, your A1C must be controlled by diet or stable doses of diabetes medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that efinopegdutide has been tested for safety in treating non-alcoholic fatty liver disease. In earlier studies, patients generally tolerated it well. Some experienced mild to moderate side effects, but these were not serious, suggesting that efinopegdutide could be safe to use.

For semaglutide, more safety information is available. Studies have shown that it does not cause any new safety issues. Most side effects were mild and expected, with no serious health problems reported. The FDA has already approved semaglutide for similar liver conditions, further supporting its safety.

Overall, both treatments appear safe based on current research. However, anyone considering joining the trial should discuss the possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about efinopegdutide for treating Nonalcoholic Steatohepatitis (NASH) because it offers a unique approach compared to current treatments. Unlike standard options that primarily focus on managing symptoms or associated conditions, efinopegdutide is designed to target NASH more directly through its action as a glucagon-like peptide-1 (GLP-1) receptor agonist, potentially improving liver health and reducing fat accumulation. Moreover, efinopegdutide is administered via a once-weekly subcutaneous injection with a dose-escalation regimen, which may enhance patient adherence and convenience. This novel mechanism and delivery method make efinopegdutide a promising candidate for effectively managing NASH.

What evidence suggests that this trial's treatments could be effective for NASH?

This trial will compare the effects of efinopegdutide and semaglutide on nonalcoholic steatohepatitis (NASH). Research has shown that efinopegdutide may help treat nonalcoholic fatty liver disease (NAFLD). In one study, patients who took efinopegdutide 10 mg weekly experienced a much larger decrease in liver fat compared to those who took semaglutide 1 mg weekly. This suggests that efinopegdutide might effectively reduce liver fat, a major issue in NASH.

Regarding semaglutide, studies indicate it can improve liver fibrosis, which is the thickening and scarring of liver tissue, without worsening liver inflammation in some patients. However, it did not significantly improve fibrosis or completely resolve NASH in all cases. Both treatments show promise in addressing liver problems related to NASH, but results can vary. Participants in this trial will receive either efinopegdutide, semaglutide, or a placebo to evaluate their effects on NASH. ^{1 2 3 5 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 NASH, a type of liver disease where fat builds up in the liver. Participants should not have other types of liver diseases, uncontrolled Type II diabetes, or a history of cirrhosis or pancreatitis. Those who've had bariatric surgery within the last 5 years are also excluded.

Inclusion Criteria

I have NASH.

Exclusion Criteria

My type II diabetes is not under control.

I have not had liver diseases other than NASH.

I have not had bariatric surgery in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either efinopegdutide or placebo administered by SC injection once weekly for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Efinopegdutide
• Placebo
• Semaglutide

Trial Overview The study tests how effective Efinopegdutide is compared to a placebo in treating NASH. It aims to see if Efinopegdutide can reduce signs of NASH without worsening liver scarring. Semaglutide's effects may also be observed as part of the study.

How Is the Trial Designed?

Group I: Efinopegdutide 7mg Experimental Treatment 1 Intervention

Efinopegdutide administered by SC injection once weekly for 52 weeks in a dose-escalation regimen of 2 mg for 4 weeks, 4 mg for 4 weeks, and 7 mg for 44 weeks.

Group II: Efinopegdutide 4mg Experimental Treatment 1 Intervention

Efinopegdutide administered by subcutaneous (SC) injection once weekly for 52 weeks in a dose-escalation regimen of 2 mg for 4 weeks and 4mg for 48 weeks.

Group III: Efinopegdutide 10mg Experimental Treatment 1 Intervention

Efinopegdutide administered by SC injection once weekly for 52 weeks in a dose-escalation regimen of 2 mg for 4 weeks, 4 mg for 4 weeks, 7 mg for 4 weeks, and 10 mg for 40 weeks.

Group IV: Semaglutide 2.4 mg Active Control 1 Intervention

Semaglutide administered by SC injection once weekly for 52 weeks in a dose-escalation regimen of 0.25 mg for 4 weeks, 0.5 mg for 4 weeks, 1.0 mg for 4 weeks, 1.7 mg for 4 weeks, and 2.4 mg for 36 weeks.

Group V: Placebo Placebo Group 1 Intervention

Placebo administered by SC injection once weekly for 52 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 I study involving 37 participants with varying degrees of renal impairment, cotadutide showed similar pharmacokinetics across all renal function groups, indicating that its absorption and concentration in the body are not significantly affected by kidney function.

The safety profile of cotadutide was favorable, with most treatment-emergent adverse events being mild to moderate, suggesting that dose adjustments may not be necessary for individuals with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety of Cotadutide, a GLP-1 and Glucagon Receptor Dual Agonist, in Individuals with Renal Impairment: A Single-Dose, Phase I, Bridging Study. Klein, G., Petrone, M., Yang, Y., 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]

In a phase 2 trial involving 71 patients with NASH-related cirrhosis, semaglutide did not significantly improve liver fibrosis or lead to NASH resolution compared to placebo after 48 weeks.

The safety profile of semaglutide was similar to that of the placebo, with no new safety concerns identified, and common side effects included nausea and diarrhea, but overall liver and kidney function remained stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Loomba, R., Abdelmalek, MF., Armstrong, MJ., et al.[2023]

In a study using non-obese mice with nonalcoholic steatohepatitis (NASH), the GLP-1 analogue exendin-4 significantly reduced liver fat accumulation and inflammation after four weeks of treatment, indicating its potential efficacy in managing NASH.

Exendin-4 works by inhibiting the influx of free fatty acids into the liver and reducing oxidative stress, which helps to alleviate the symptoms of hepatic steatosis and inflammation associated with NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice. Yamamoto, T., Nakade, Y., Yamauchi, T., et al.[2022]

The LEAN trial is a phase II study investigating the efficacy of liraglutide, a GLP-1 analogue, in improving liver histology in patients with non-alcoholic steatohepatitis (NASH) over 48 weeks, involving 52 participants with biopsy-confirmed NASH.

The primary outcome will assess the proportion of patients showing improvement in liver histology, specifically the disappearance of active NASH and no worsening of fibrosis, highlighting liraglutide's potential as a treatment option for this common liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide efficacy and action in non-alcoholic steatohepatitis (LEAN): study protocol for a phase II multicentre, double-blinded, randomised, controlled trial. Armstrong, MJ., Barton, D., Gaunt, P., et al.[2022]

In a phase 2 trial involving 52 patients with non-alcoholic steatohepatitis, liraglutide treatment resulted in a significant resolution of the condition in 39% of patients compared to only 9% in the placebo group, indicating its efficacy in treating this liver disease.

Liraglutide was found to be safe and well-tolerated, with most adverse events being mild to moderate, although gastrointestinal issues were more common in the liraglutide group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Armstrong, MJ., Gaunt, P., Aithal, GP., et al.[2022]

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]

GLP-1 receptor (GLP-1R) agonists, which are effective in treating type 2 diabetes and obesity, show promise as potential therapeutic agents for nonalcoholic steatohepatitis (NASH), a severe form of fatty liver disease.

The article discusses the complex pathogenesis of NASH and highlights the pharmacological effects of GLP-1 mimetics, including their mechanisms of action, suggesting they could be beneficial in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis. Chen, Y., Xu, YN., Ye, CY., et al.[2023]

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]

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. sciencedirect.com sciencedirect.com/science/article/pii/S0168827823003422

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.

4. 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).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06465186

NCT06465186 | A Clinical Study of Efinopegdutide in ... Researchers are looking for ways to treat a type of liver disease caused by elevated liver fat, called metabolic dysfunction-associated steatohepatitis (MASH).

6. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(23)00342-2/fulltext

A phase IIa active-comparator-controlled study to evaluate ... A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease.