What side effects are associated with this type of intervention?

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) often target metabolic inflammation, glucose, and lipid metabolism. These treatments can include farnesoid X receptor agonists, peroxisome proliferator-activated receptor-α/δ agonists, and AdipoR small-molecule agonists. Known side effects of these treatments can include gastrointestinal issues, such as nausea and diarrhea, as well as potential liver enzyme elevations. Additionally, some treatments may cause muscle toxicity or neurocognitive symptoms, although these are generally rare. It is important for patients to discuss these potential side effects with their healthcare provider to determine the best treatment plan.

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, several drugs are being studied for their potential benefits in managing this condition. LY3849891 is currently under investigation for its safety and tolerability in patients with NAFLD, particularly those with the PNPLA3 I148M genotype. Other drugs that have been explored for liver-related conditions include statins, which have shown some promise in reducing liver fat and inflammation, and GLP-1 receptor agonists like liraglutide and semaglutide, which have demonstrated efficacy in weight reduction and improvement in liver enzymes. These treatments, while not specifically approved for NAFLD, are part of ongoing research efforts to find effective therapies for this condition.

What other types of research exist?

Promising novel alternatives to LY3849891 for NAFLD patients include: 1) LY2405319, an engineered FGF21 variant that enhances hepatic mitochondrial function and attenuates NASH progression. 2) Polyethylene glycol 3350 (PEG 3350) and lactulose, which have shown efficacy in reducing hepatic inflammation and steatosis in preclinical studies. 3) FXR agonists like Px-102/Px-104, currently in phase IIa trials, which target metabolic pathways involved in NAFLD. These alternatives have demonstrated potential in preclinical or early clinical studies and may offer new therapeutic options for NAFLD patients.

← Back to Search

Unknown

LY3849891 for Non-alcoholic Fatty Liver Disease

Phase 1

Recruiting

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

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

Must have

Participants must be carriers of the PNPLA3 I148M allele

For participants with T2DM, hemoglobin A1c (HbA1c) <8%

Must not have

Participants must not have a contraindication to MRI examinations, such as persons with cardiac pacemaker and implants made out of metal (for example, cochlear implant, nerve stimulators, magnetic vascular clips, and metallic heart valve) or other contraindications for MRI

Participants must not have had active cancer within the last 5 years

Timeline

Screening 3 weeks

Treatment Varies

Follow Up predose through week 26

Summary

This trial is testing a new medication called LY3849891 in people with fatty liver disease who have a specific genetic variant. The study will check how the drug affects liver fat and how the body processes it using blood tests and imaging.

Who is the study for?

This trial is for adults with nonalcoholic fatty liver disease who are overweight or obese, may or may not have type 2 diabetes (with HbA1c <8%), and carry the PNPLA3 I148M gene variant. Women must be non-childbearing due to surgery or menopause. Participants should not have a history of significant alcohol/substance abuse, active cancer in the last 5 years, uncontrolled high blood pressure, severe kidney issues, type 1 diabetes, MRI contraindications like metal implants, or serious heart conditions.

What is being tested?

The study tests LY3849891's safety and effects on liver fat in participants with a specific genetic background related to fatty liver disease. It involves two parts: one where doses increase to find safe levels and another where repeated doses are given over up to 32 weeks. Effects will be measured using blood tests and MRI scans of the liver.

What are the potential side effects?

While specific side effects aren't listed here, common ones from similar trials include gastrointestinal discomforts such as nausea or diarrhea; potential allergic reactions; headaches; fatigue; and possible impacts on liver enzymes which will be monitored through regular blood testing.

Eligibility Criteria

Inclusion Criteria

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

Select...

I carry the PNPLA3 I148M gene variant.

Select...

My latest HbA1c level is below 8%.

Exclusion Criteria

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

Select...

I do not have any implants or conditions that prevent me from having an MRI.

Select...

I have not had active cancer in the last 5 years.

Select...

I do not have type 1 diabetes.

Select...

I haven't had a heart attack, stroke, or been hospitalized for heart failure recently.

Select...

My blood pressure is under control.

Select...

My kidney function is normal or only mildly reduced.

Select...

My liver is healthy without any signs of cirrhosis or disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ predose through week 26

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~predose through week 26

This trial's timeline: 3 weeks for screening, Varies for treatment, and predose through week 26 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Part A: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

Part B: Pharmacodynamics (PD): Relative change from baseline on liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF)

Secondary study objectives

Part A & B: PD: Liver fat content at baseline and specified timepoints measured by MRI-PDFF

Part A & B: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891

Part A & B: Part A & B: PK: Area Under the Concentration Versus Time Curve (AUC) of LY3849891

+2 more

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: LY3849891 (Part B)Experimental Treatment1 Intervention

Repeated doses of LY3849891 administered SC.

Group II: LY3849891 (Part A)Experimental Treatment1 Intervention

Single ascending doses of LY3849891 administered subcutaneously (SC).

Group III: Placebo (Part A)Placebo Group1 Intervention

Placebo administered SC.

Group IV: Placebo (Part B)Placebo Group1 Intervention

Placebo administered SC.

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) often target metabolic pathways to reduce liver fat and inflammation. For instance, pioglitazone, a PPAR-gamma agonist, improves insulin sensitivity and reduces liver fat. Vitamin E, an antioxidant, helps reduce oxidative stress and inflammation in the liver. SGLT2 inhibitors, primarily used for diabetes, also show promise in reducing liver fat and improving liver function by promoting glucose excretion. These treatments are crucial for NAFLD patients as they address the underlying metabolic dysfunctions and help prevent progression to more severe liver diseases. The study drug LY3849891, although its mechanism is unknown, is being evaluated for similar benefits in reducing liver fat and improving liver health.

Nutrition and Nonalcoholic Fatty Liver Disease: Current Perspectives.