Semaglutide for Non-alcoholic Steatohepatitis

(ESSENCE Trial)

Recruiting at 844 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must not be taking: Vitamin E, Pioglitazone, GLP-1 RAs, others

Disqualifiers: Chronic liver diseases, Alcohol use, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 24

Duration: 240 weeks

1205 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Semaglutide is a medicine studied in patients with NASH. Semaglutide is a well-known medicine, which is already used by doctors to treat type 2 diabetes in many countries. Participants will either get semaglutide or a dummy medicine - which treatment participants get is decided by chance. Participants will need to inject themselves with medicine under the skin. Participants will need to do this once a week. The study will last for about 5 years. Participants will have up to 21 clinic visits and 9 phone calls with the clinical staff during the study. Some of the clinic visits may be spread over more than one day. Participants with other chronic liver diseases cannot take part in this study. Women cannot take part in the study if they are pregnant, breast-feeding or plan to become pregnant during the study period.

Will I have to stop taking my current medications?

The trial requires that certain medications be at a stable dose for at least 90 days before the screening visit. If you are taking vitamin E, pioglitazone, GLP-1 RAs, glucose-lowering agents, lipid-lowering medications, or weight loss medications, they must be stable according to the investigator's opinion. You may need to adjust your medications to meet these criteria.

Is semaglutide safe for humans?

Semaglutide has been studied for various conditions, including non-alcoholic steatohepatitis (NASH), and is generally considered safe. It is known to cause significant weight loss and improve liver conditions without severe side effects, making it a safer option compared to some other treatments. ^{1 2 3 4 5}

How is the drug semaglutide unique in treating non-alcoholic steatohepatitis (NASH)?

Semaglutide is unique in treating NASH because it not only improves liver inflammation and fat accumulation but also leads to significant weight loss, which is beneficial for liver health. Unlike other treatments, semaglutide has shown exclusive potential in resolving NASH, although it may need to be combined with other agents for reversing advanced fibrosis. ^{1 2 4 5 6}

What data supports the effectiveness of the drug semaglutide for treating non-alcoholic steatohepatitis (NASH)?

Research shows that semaglutide can lead to significant improvements in liver health for patients with NASH, including reducing liver fat and inflammation. It is also noted for its safety and ability to cause weight loss, which can further benefit liver health. ^{1 2 4 5 6}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

Adults with a specific liver condition called NASH and fibrosis stages 2 or 3 can join this study. They must have evidence of NASH from a recent biopsy, not be on certain unstable medications, and cannot have other chronic liver diseases or excessive alcohol use. Pregnant women or those planning pregnancy are excluded.

Inclusion Criteria

My liver disease score is 4 or higher, with signs of fat, inflammation, and cell damage.

My liver fibrosis is at stage 2 or 3 according to a specialist's review.

My liver fibrosis is at stage 2 or 3 according to a biopsy.

Exclusion Criteria

You drink too much alcohol or have an addiction to alcohol.

Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V2A) or any known presence of HCV RNA or HBsAg within 2 years of screening (V2A).

I haven't changed my dose of vitamin E, pioglitazone, or NASH medication in the last 90 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive semaglutide or placebo administered subcutaneously once weekly

240 weeks

21 visits (in-person), 9 phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Semaglutide

Trial Overview The trial is testing Semaglutide, already used for type 2 diabetes, against a placebo to see if it helps with NASH. Participants will inject themselves weekly and the study spans about five years with regular clinic visits and phone check-ins.

How Is the Trial Designed?

Group I: Semaglutide OW (once weekly ) Experimental Treatment 1 Intervention

Semaglutide administrated subcutaneously once weekly

Group II: Placebo Placebo Group 1 Intervention

Placebo administrated subcutaneously once weekly

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

In a study using Ldlr-/-.Leiden mice, semaglutide significantly reduced liver fat and inflammation by 74% and 73% respectively, indicating its potential effectiveness in treating non-alcoholic steatohepatitis (NASH).

While semaglutide improved liver health by reversing certain gene expressions associated with NASH, it did not significantly affect liver fibrosis, suggesting that it may need to be combined with other treatments for advanced fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-/-.Leiden Mice. Inia, JA., Stokman, G., Morrison, MC., 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 systematic review of 8 studies involving 2413 patients, 24 weeks of semaglutide treatment significantly reduced liver enzymes (alanine transaminase and aspartate transaminase) and improved liver fat content and stiffness, indicating its efficacy in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

Despite its benefits, semaglutide treatment was associated with a higher risk of serious gastrointestinal adverse events, such as nausea and vomiting, highlighting the need for careful monitoring of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Bandyopadhyay, S., Das, S., Samajdar, SS., et al.[2023]

Semaglutide and obeticholic acid (OCA) both show histological improvement in patients with non-alcoholic fatty liver disease (NAFLD), but only semaglutide leads to complete resolution of non-alcoholic steatohepatitis (NASH).

Semaglutide is considered the safer option, promoting significant weight loss and better outcomes for hepatic steatosis, while OCA can improve NASH-associated fibrosis but may cause side effects like dyslipidemia and severe itching, necessitating caution in certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the Efficacy and Safety of Obeticholic Acid and Semaglutide in Patients With Non-Alcoholic Fatty Liver Disease: A Systematic Review. Ahmed, NR., Kulkarni, VV., Pokhrel, S., et al.[2022]

In a phase II trial involving 108 patients with non-alcoholic steatohepatitis (NASH), the combination of semaglutide with cilofexor and/or firsocostat was found to be safe and well tolerated, with similar rates of adverse events across treatment groups.

The combination therapies resulted in greater improvements in liver steatosis and liver biochemistry compared to semaglutide alone, suggesting that targeting multiple mechanisms may enhance treatment efficacy for NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial. Alkhouri, N., Herring, R., Kabler, H., et al.[2022]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-/-.Leiden Mice. [2023]

2. 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]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. [2023]

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

Semaglutide for the treatment of non-alcoholic steatohepatitis: Trial design and comparison of non-invasive biomarkers. [2021]

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

Comparing the Efficacy and Safety of Obeticholic Acid and Semaglutide in Patients With Non-Alcoholic Fatty Liver Disease: A Systematic Review. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial. [2022]