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

• ClinicalTrials.gov Identifier: NCT06007651
• Recruitment Status: Recruiting
• First Posted: August 23, 2023
• Last Update Posted: October 18, 2023
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Dyslipidemias; Non-Alcoholic Fatty Liver Disease	Drug: LY3885125; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: August 10, 2023
• Estimated Primary Completion Date: April 15, 2025
• Estimated Study Completion Date: April 15, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Part A: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration [ Time Frame: Baseline up to 49 weeks (Part A) ]
   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
2. Part B: Number of Participants with One or More SAEs Considered by the Investigator to be Related to Study Drug Administration [ Time Frame: Baseline up to 62 weeks (Part B) ]
   Part B: A summary of SAEs and other non-serious AEs, regardless of causality, will be reported in the Reported Adverse Events module

Secondary Outcome Measures :

1. Part A & B: Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of LY3885125 [ Time Frame: Baseline up to 49 weeks (Part A) and Baseline up to 62 weeks (Part B) ]
   Part A & B: PK: AUC of LY3885125
2. Part A & B: PK: Maximum Observed Plasma Concentration (Cmax) of LY3885125 [ Time Frame: Baseline up to 49 weeks (Part A) and Baseline up to 62 weeks (Part B) ]
   Part A & B: PK: Cmax of LY3885125
3. Part A & B: PK: Time of Maximum Observed Concentration (Tmax) of LY3885125 [ Time Frame: Baseline up to 49 weeks (Part A) and Baseline up to 62 weeks (Part B) ]
   Part A & B: PK: Tmax of LY3885125
4. Part A & B: Pharmacodynamics (PD): Change From Baseline in Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) [ Time Frame: Baseline up to 49 weeks (Part A) and Baseline up to 62 weeks (Part B) ]
   Part A & B: PD: Change From Baseline in PCSK9
5. Part A & B: PD: Change From Baseline in apolipoprotein B (ApoB) [ Time Frame: Baseline up to 49 weeks (Part A) and Baseline up to 62 weeks (Part B) ]
   Part A & B: PD: Change From Baseline in ApoB
6. Part B only: PD: Change of Liver Fat Content From Baseline by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) [ Time Frame: Baseline up to 62 weeks (Part B) ]
   Part B only: PD: Change of Liver Fat Content From Baseline by MRI-PDFF

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@Lilly.com

Locations

United States, Texas

Worldwide Clinical Trials, Early Phase Services LLC; Recruiting

San Antonio, Texas, United States, 78217

Contact 210-635-1500

Principal Investigator: Alan Hand, MD

Sponsors and Collaborators

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

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT06007651
• Other Study ID Numbers: 18769; J4N-MC-YFAA ( Other Identifier: Eli Lilly and Company )
• First Posted: August 23, 2023
• Last Update Posted: October 18, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Dyslipidemias; Digestive System Diseases; Lipid Metabolism Disorders; Metabolic Diseases