A Study of LY3885125 in Participants With Dyslipidemia or Non-Alcoholic Fatty Liver Disease (NAFLD)

A Phase 1, Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial of LY3885125 to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Ascending Dose in Participants With Dyslipidemia and Repeat-Doses in Participants With NAFLD

The main purpose of this study is to evaluate the safety and tolerability of LY3885125 after administration of single ascending doses in participants with dyslipidemia (part A) and multiple doses in participants with non-alcoholic fatty liver disease (part B). Blood tests will be performed to check how much LY3885125 gets into the bloodstream and how long it takes the body to eliminate it.

The study will last up to approximately 49 weeks for part A and 62 weeks for part B, for a total of approximately 111 weeks.

Study Overview

• Status: Terminated
• Conditions: Dyslipidemias; Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Placebo; Drug: LY3885125

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Parts A & B

• Males, or females of not of childbearing potential,
• On a stable diet for the 3 months prior to randomization and willing to continue the same stable diet during the study.

Part A

• Dyslipidemia with the following fasted blood levels at screening: 150 mg/dL ≤ triglycerides <500 mg/dL, AND LDL-cholesterol ≥100 mg/dL,
• Body mass index (BMI) in range of 18.5 to 45.0 kg/m2. Part B
• NAFLD with liver fat content ≥8% as determined by magnetic resonance imaging proton density fat fraction (MRI-PDFF),
• BMI in range of 27 to 45.0 kg/m2

Exclusion Criteria:

Parts A & B

• History or presence of medical illness including, but not limited to, any cardiovascular, thromboembolism or bleeding disorder, hepatic, respiratory, hematological, endocrine, immune, psychiatric, or neurological disease, convulsions, or any clinically significant laboratory abnormality that, in the judgment of the Investigator, indicate a medical problem that would preclude study participation,
• Uncontrolled hypertension with a resting blood pressure ≥ 160 mmHg systolic or ≥ 100 mmHg diastolic at visit 1,
• Alanine transaminase (ALT) or aspartate aminotransferase (AST) >3.0 × ULN for the reference range,
• Alkaline phosphatase (ALP) >1.5 × ULN for the reference range,
• Total bilirubin (TBL) >1.5 × ULN for the reference range,
• Taken drugs associated with hepatic steatosis (e.g., amiodarone, valproic acid, methotrexate, tamoxifen) for more than 2 weeks in the 3 months prior to screening visit,
• Type 1 diabetes mellitus (T1DM) or any other type of diabetes mellitus other than T2DM,
• Poorly controlled T2DM with glycated hemoglobin (HbA1c) of >9.0%,
• Treatment with GLP-1 RA and GIP/GLP-1 RA and approved or experimental agents that target PCSK9 within 9 months prior to screening visit.

Part B

• Evidence of other forms of chronic liver disease,
• Initiated treatment with, or changed dose of, medications that may cause significant weight gain or weight loss, within 3 months prior to the screening visit,
• Have a self-reported change in body weight >5 kg (11 pounds) within 3 months prior to screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3885125 (Part A); Single ascending doses of LY3885125 administered subcutaneously (SC)	Drug: LY3885125; Administered SC
Placebo Comparator: Placebo (Part A); Placebo administered SC	Drug: Placebo; Administered SC
Experimental: LY3885125 (Part B); Repeat doses of LY3885125 administered SC	Drug: LY3885125; Administered SC
Placebo Comparator: Placebo (Part B); Placebo administered SC	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of Participants With One or More Serious Adverse Event(s) Considered by the Investigator to be Related to Study Drug Administration	Part A: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module	Baseline up to 36 weeks (Part A)
Part B: Number of Participants With One or More SAEs Considered by the Investigator to be Related to Study Drug Administration	Part B: A summary of SAEs and other non-serious AEs, regardless of causality, will be reported in the Reported Adverse Events module	Baseline up to 36 weeks (Part B)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of LY3885125	Part A: PK: AUC of LY3885125	Baseline up to 36 weeks (Part A)
Part A: PK: Maximum Observed Plasma Concentration (Cmax) of LY3885125	Part A: PK: Cmax of LY3885125	Baseline up to 36 weeks (Part A)
Part A: PK: Time of Maximum Observed Concentration (Tmax) of LY3885125	Part A: PK: Tmax of LY3885125	Baseline up to 36 weeks (Part A)
Part A: Pharmacodynamics (PD): Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)	Part A: PD: Change From Baseline in PCSK9	Baseline up to Day 169 (Part A)
Part A: PD: Change From Baseline in Apolipoprotein B (ApoB)	Part A: PD: Change From Baseline in ApoB	Baseline up to Day 169 (Part A)
Part B Only: PD: Change of Liver Fat Content From Baseline by MRI-PDFF	Part B Only: PD: Change of Liver Fat Content from Baseline by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF)	Baseline up to 62 weeks (Part B)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Actual): February 12, 2025
• Study Completion (Actual): February 12, 2025

Study Registration Dates

• First Submitted: August 18, 2023
• First Submitted That Met QC Criteria: August 18, 2023
• First Posted (Actual): August 23, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Digestive System Diseases; Liver Diseases; Lipid Metabolism Disorders; Fatty Liver; Nutritional and Metabolic Diseases; Non-alcoholic Fatty Liver Disease; Dyslipidemias
• Other Study ID Numbers: 18769; J4N-MC-YFAA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No