What side effects are associated with this type of intervention?

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD), such as GLP-1 receptor agonists like Semaglutide, often cause gastrointestinal side effects including nausea, vomiting, and diarrhea. These treatments also promote weight loss, which can be beneficial but may require monitoring for nutritional deficiencies. Liver-targeting medications like NNC0194-0499 may cause liver enzyme elevations and potential hepatotoxicity. Combining these treatments could enhance their efficacy but necessitates careful monitoring for compounded side effects.

What prior FDA approvals exist?

As of now, there are no FDA-approved medications specifically for the treatment of Non-alcoholic Fatty Liver Disease (NAFLD). However, drugs like Semaglutide, a GLP-1 receptor agonist, have shown promise in clinical trials for their potential to reduce liver damage and aid in weight loss, which is beneficial for NAFLD patients. Semaglutide is already approved for the treatment of type 2 diabetes and obesity. Other treatments under investigation include combinations of liver-targeting agents and GLP-1 receptor agonists, similar to the trial involving NNC0194-0499 and Semaglutide.

What other types of research exist?

Promising novel alternatives for NAFLD treatment in 2024 include: 1) Tirzepatide, a dual GIP and GLP-1 receptor agonist, which has shown significant weight loss and metabolic benefits. 2) Resmetirom (MGL-3196), a thyroid hormone receptor-beta agonist, which targets liver fat reduction and improves liver histology. 3) Lanifibranor, a pan-PPAR agonist, which has demonstrated efficacy in improving liver fibrosis and inflammation. These agents offer different mechanisms of action that may complement or provide alternatives to NNC0194-0499 and Semaglutide.

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NNC0194-0499 + Semaglutide for Fatty Liver Disease

Phase 2

Waitlist Available

Research Sponsored by Novo Nordisk A/S

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histological evidence of fibrosis stage 2, 3 or 4 according to the NASH CRN classification based on a central pathologist evaluation of the baseline liver biopsy.

Histological non-alcoholic fatty liver disease (NAFLD) activity score (NAS) greater than or equal to 4 for subjects with F2/F3 or greater than or equal to 3 for subjects with F4 based on a central pathologist evaluation of the baseline liver biopsy. All subjects must have a score of 1 or more in steatosis, lobular inflammation and hepatocyte ballooning.

Must not have

Documented causes of chronic liver disease other than NAFLD.

Presence or history of ascites more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at V2A.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline (week 0) to week 59

Summary

This trial is testing if combining two medicines, NNC0194-0499 and semaglutide, can reduce liver damage in people with non-alcoholic steatohepatitis (NASH). Semaglutide, already used for diabetes and weight loss, and NNC0194-0499 work differently but may be more effective together. Another combination being tested includes semaglutide and NNC0174-0833. Participants will receive regular injections and undergo liver biopsies to measure the treatment's effectiveness.

Who is the study for?

Adults with a certain liver condition called NASH and evidence of liver scarring (fibrosis stages 2-4) can join this study. They must have had a recent biopsy confirming the disease. Pregnant women or those planning pregnancy, heavy drinkers, and people on unstable doses of certain medications are excluded.

What is being tested?

The trial is testing if two drugs, NNC0194-0499 and semaglutide, can help reduce liver damage in NASH patients when used together or separately compared to placebo injections. Participants will receive weekly injections for about 19 months with regular clinic visits and calls.

What are the potential side effects?

Possible side effects include reactions at the injection site, gastrointestinal issues like nausea or diarrhea, potential low blood sugar levels especially in those taking other diabetes medicines, and increased heart rate.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My liver fibrosis is at stage 2, 3, or 4.

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My liver disease score is high enough to meet the trial's requirements.

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My liver fibrosis is at stage 2, 3, or 4.

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My liver disease score is high enough to meet the trial's requirements.

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My liver fibrosis is at stage 2, 3, or 4.

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My liver disease score is high enough to meet the trial's requirements.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My chronic liver disease is not due to fatty liver.

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I have had serious liver problems or a liver transplant.

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I haven't taken GLP-1 receptor agonists in the last 90 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from baseline (week 0) to week 59

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from baseline (week 0) to week 59

This trial's timeline: 3 weeks for screening, Varies for treatment, and from baseline (week 0) to week 59 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Improvement in liver fibrosis and no worsening of NASH (Yes/No)

Secondary study objectives

Change in ALT (alanine aminotransferase)

Change in AST (aspartate aminotransferase)

Change in ELF (Enhanced Liver Fibrosis) score

+21 more

Trial Design

10Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: NNC0194-0499 7.5 mg + semaglutide 2.4 mgExperimental Treatment2 Interventions