Lepodisiran for Liver Dysfunction

Recruiting at 3 trial locations

Overseen By Eric Lawitz

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Disqualifiers: Cardiovascular, Respiratory, Renal, Psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called lepodisiran to understand its behavior in the body, particularly in individuals with liver issues. Researchers aim to determine how much of the drug enters the bloodstream and how quickly the body clears it. The trial will also assess how well participants tolerate lepodisiran and identify any potential side effects. It suits individuals with diagnosed liver problems for more than six months or those without liver issues who are otherwise healthy. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that lepodisiran is likely to be safe for humans?

Research has shown that lepodisiran was well tolerated in earlier studies. In one study, lepodisiran led to long-lasting reductions in a type of fat in the blood without causing serious side effects, suggesting it may be safe for humans. However, as this trial is in an early phase for liver issues, further research is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Lepodisiran because it offers a unique approach to treating liver dysfunction. Unlike traditional treatments that focus on managing symptoms or slowing disease progression, Lepodisiran is designed to be administered subcutaneously, potentially providing a more direct and efficient delivery of the medication. This could lead to improved outcomes by targeting the liver more effectively. The new mechanism of action and delivery method set it apart from existing options, offering hope for better management of liver dysfunction in the future.

What evidence suggests that lepodisiran might be an effective treatment for liver dysfunction?

Research has shown that lepodisiran can significantly reduce lipoprotein(a), a type of fat in the blood, for an extended period after administration. Studies have found that the drug lowers these fats in a dose-dependent manner. Reducing lipoprotein(a) is important because high levels are linked to heart disease. The drug has kept these levels low for months, suggesting potential benefits for conditions related to high lipoprotein(a). However, its effects on liver problems remain under investigation in this trial, where participants will receive different dosages of lepodisiran. ^{1 2 4 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for people with varying degrees of liver function, from normal to severe impairment. It's also open to healthy participants. The study aims to understand how a drug called Lepodisiran behaves in different liver conditions.

Inclusion Criteria

I am healthy with normal liver function.

My weight is at least 55 kg and my BMI is between 19.0 and 42.0.

I have liver problems that have lasted more than 6 months.

Exclusion Criteria

Have known allergies to lepodisiran, related compounds, or any components of the formulation

Have a history of, or current, psychiatric disorders

Have severe atopy or a history of clinically significant multiple or severe drug allergies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single-dose subcutaneous injection of Lepodisiran

1 day

1 visit (in-person)

Follow-up

Participants are monitored for pharmacokinetics and side effects

Up to 9 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lepodisiran

Trial Overview Lepodisiran is being tested for its absorption and clearance from the body when injected under the skin. Participants with different levels of liver health will be compared over a period lasting up to 9 weeks.

How Is the Trial Designed?

Group I: Lepodisiran Group 4 Experimental Treatment 1 Intervention

Lepodisiran administered SC

Group II: Lepodisiran Group 3 Experimental Treatment 1 Intervention

Lepodisiran administered SC

Group III: Lepodisiran Group 2 Experimental Treatment 1 Intervention

Lepodisiran administered SC

Group IV: Lepodisiran Group 1 Experimental Treatment 1 Intervention

Lepodisiran administered subcutaneously (SC)

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a Phase 1 study involving 55 subjects, saroglitazar magnesium was found to be safe and well tolerated across varying degrees of hepatic impairment, indicating its potential for treating liver conditions.

While mild and moderate hepatic impairment did not significantly affect the drug's pharmacokinetics, severe hepatic impairment led to a threefold increase in drug exposure, suggesting that careful monitoring or dose adjustments may be necessary for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety Evaluation of Single-Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment. Lawitz, E., Parmar, D., Momin, T., et al.[2023]

In a systematic review of 10 studies involving patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), treatment with 4 mg saroglitazar significantly reduced liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST), indicating improved liver function.

Saroglitazar also led to significant improvements in liver stiffness and metabolic parameters such as glycated hemoglobin, total cholesterol, and triglycerides, suggesting it is an effective and safe treatment option for managing NAFLD and NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

In a study of 38 elderly patients with drug-induced liver injury (DILI), approximately 32.3% of DILI-drug pairs were deemed 'avoidable' using the Liverpool adverse drug reactions avoidability tool (LAAT), indicating potential for prevention strategies.

The findings suggest that a significant portion of DILI cases in this population could be prevented, highlighting the importance of using tools like LAAT for improving patient safety and reducing healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score. Danjuma, MI., Almasri, H., Alshokri, S., et al.[2020]

The study identified 504 cases of drug-induced liver injury (DILI) associated with antibody-drug conjugates (ADCs) from the FAERS database, indicating a potential safety concern with these treatments.

Specific ADCs, including trastuzumab emtansine and enfortumab vedotin, were linked to DILI, suggesting the need for further research to understand the mechanisms and develop preventive strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacovigilance study on drug-induced liver injury associated with antibody-drug conjugates (ADCs) based on the food and drug administration adverse event reporting system. Sun, C., Yang, X., Tang, L., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06916078

NCT06916078 | A Study of Lepodisiran (LY3819469) in ... The main purpose of this study is to evaluate how much lepodisiran gets into the blood stream and how long it takes the body to get rid of it.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40162643/

Lepodisiran - A Long-Duration Small Interfering RNA ... Conclusions: Lepodisiran reduced mean serum concentrations of lipoprotein(a) from 60 to 180 days after administration. (Funded by Eli Lilly; ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2811935

Lepodisiran, an Extended-Duration Short Interfering RNA ... Lepodisiran was well tolerated and produced dose-dependent, long-duration reductions in serum lipoprotein(a) concentrations in this phase 1 trial.

4. withpower.com withpower.com/trial/phase-1-liver-diseases-3-2025-5f1e9

Lepodisiran for Liver Dysfunction In a study of 38 elderly patients with drug-induced liver injury (DILI), approximately 32.3% of DILI-drug pairs were deemed 'avoidable' using the Liverpool ...

5. trials.lilly.com trials.lilly.com/en-US/trial/591635

A Study of Lepodisiran (LY3819469) in Participants With ... The main purpose of this study is to evaluate how much lepodisiran gets into the blood stream and how long it takes the body to get rid of it.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10641766/

Lepodisiran, an Extended-Duration Short Interfering RNA ... Lepodisiran was well tolerated and produced dose-dependent, long-duration reductions in serum lipoprotein(a) concentrations in this phase 1 trial.

7. acc.org acc.org/Latest-in-Cardiology/Clinical-Trials/2025/03/27/18/03/alpaca

A Study of Lepodisiran in Participants With Elevated ... Ongoing studies will determine the clinical and safety profile of this promising therapy. This is yet another exciting potential tool, which may ...