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

Trial Summary

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 Lepodisiran safe for humans?

There is no specific safety data available for Lepodisiran in the provided research articles. ^{1 2 3 4 5}

How is the drug Lepodisiran different from other treatments for liver dysfunction?

Lepodisiran is unique because it is being evaluated specifically for liver dysfunction, whereas other treatments like saroglitazar magnesium are studied for broader liver conditions such as non-alcoholic fatty liver disease. Additionally, Lepodisiran's specific mechanism of action or administration details are not provided, making it distinct from other known treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

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 when given as a subcutaneous (SC) injection under the skin to participants with mild, moderate, or severe liver function impairment compared to participants with normal liver function. The study will also evaluate how well lepodisiran is tolerated and what side effects may occur in these participants. The study will last up to approximately 9 weeks, excluding screening.

Research Team

Contact Lilly at 1-800-LillyRx (1-800-545-5979)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Analysis of drug-induced liver-related adverse event trend reporting between 1997 and 2019. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Female gender as a susceptibility factor for drug-induced liver injury. [2016]

3. England 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. [2023]

4. England 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. [2020]

5. Italy pubmed.ncbi.nlm.nih.gov

Drug-Induced Liver Injury Due To Losartan. [2022]

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

Pharmacokinetics and Safety Evaluation of Single-Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment. [2023]

7. France 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. [2023]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Enteric sorbents potentiate hepatoprotective effect of eplir in experimental toxic hepatitis]. [2016]

9. China pubmed.ncbi.nlm.nih.gov

[The active metabolite of leflunomide A771726 inhibits proliferation and collagen synthesis of hepatic stellate cell]. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

New hepato-protective agents. II. Maleopimaridyl morpholides. [2016]