Efinopegdutide for Nonalcoholic Steatohepatitis (NASH)

Recruiting at 175 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

360 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine called efinopegdutide to see if it can help people with a liver disease called non-alcoholic steatohepatitis (NASH). Researchers want to find out if this medicine can reduce the symptoms of NASH without making liver scarring worse. They are also checking how safe the medicine is and how well people can tolerate it.

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.

What data supports the effectiveness of the drug Efinopegdutide for treating Nonalcoholic Steatohepatitis (NASH)?

Research shows that drugs similar to Efinopegdutide, like semaglutide, have been effective in reducing liver fat and improving liver health in patients with conditions like NASH. These drugs work by targeting specific receptors in the body that help manage liver fat and inflammation. ^{1 2 3 4 5}

Is efinopegdutide safe for humans?

The safety of efinopegdutide, a treatment for liver conditions, has been evaluated in clinical trials. It is generally considered safe, with safety findings comparable to other similar treatments, but as with any medication, it may have side effects. ^{3 4 5 6 7}

How is the drug Efinopegdutide unique for treating NASH?

Efinopegdutide is unique because it acts as a dual agonist, targeting both the GLP-1 and glucagon receptors, which may offer a novel approach to reducing liver fat content in NASH patients compared to treatments that target only the GLP-1 receptor, like semaglutide. ^{1 3 4 8 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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 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 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]

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]

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]

References

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

Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice. [2022]

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

GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis. [2023]

3. 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]

4. 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]

5. Netherlands 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. [2023]

6. Switzerland 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. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

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

8. England 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. [2022]

9. England 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. [2022]