A Single-Ascending and Repeated Dose Study of LY3849891 in Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

NCT05395481 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 18214J3W-MC-GZOA
• Study Type: interventional
• Target: 176
• Locations: 3 countries
• Sites: 16

Brief Summary

The main purpose of this study is to evaluate the safety and tolerability of the study drug LY3849891 in participants with metabolic dysfunction-associated steatotic liver disease (MASLD) who have the patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M genotype. Blood tests and magnetic resonance imaging of the liver will be performed to determine the effects of LY3849891 on MASLD and assessment of resolution of liver fibroinflammation. Blood tests will also determine how long it takes the body to eliminate LY3849891. This is a 2-part study and may last up to 32 weeks for each participant and may include 12 visits in parts A and B.

Conditions

Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD); Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Keywords

Hepatic fibrosis; Biomarkers; Magnetic resonance imaging; Pharmacokinetics; Liver fat

Outcome Measures

Primary Outcomes (2)

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

  A summary of TEAEs and AEs, regardless of causality, will be reported in the Reported Adverse Events module

  Predose up to 26 weeks post dose

• Part B: Pharmacodynamics (PD): Mean change from baseline on liver inflammation and fibrosis measured by magnetic resonance imaging (MRI)

  PD: Mean change from baseline on liver inflammation and fibrosis content measured by MRI

  Baseline through 24 weeks

Secondary Outcomes (8)

• Part A: PD: Liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF)

  Predose through Week 26

• Part A: PK: Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC(0-inf)) of LY3849891

  Predose through Week 26

• Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891

  Predose through Week 26

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

  Predose through Week 26

• Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF

  Predose through Week 24

Study Arms (4)

LY3849891 (Part A)

EXPERIMENTAL

Single ascending doses of LY3849891 administered subcutaneously (SC)

Drug: LY3849891

LY3849891 (Part B)

EXPERIMENTAL

Repeated doses of LY3849891 administered SC

Drug: LY3849891

Placebo (Part A)

PLACEBO COMPARATOR

Placebo administered SC

Drug: Placebo

Placebo (Part B)

PLACEBO COMPARATOR

Placebo administered SC

Drug: Placebo

Interventions

LY3849891 DRUG

Administered SC

LY3849891 (Part A); LY3849891 (Part B)

Placebo DRUG

Administered SC

Placebo (Part A); Placebo (Part B)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a body mass index (BMI) within the range greater than or equal to (≥) 25 and less than (\<) 50 kilogram per square meter (kg/m²) inclusive
• Participants must have liver fat content ≥10% in Part A and ≥8% for Part B as determined by MRI-PDFF
• Participants must be carriers of the PNPLA3 I148M allele
• Participants with or without type 2 diabetes mellitus (T2DM)
• o For participants with T2DM, hemoglobin A1c (HbA1c) \<8% in Part A and \<9% in Part B
• Male participants agree to use an effective method of contraception for the duration of the study and for 90 days after the last dose of study intervention
• Women not of childbearing potential may participate and include those who are: infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as Mullerian agenesis; or those who are postmenopausal

You may not qualify if:

• Participants must not have known or suspected alcohol abuse (\>14 units/week for women and \>21 units/week for men) or active substance abuse
• Participants must not have evidence of cirrhosis or other forms of liver disease
• Participants must not have heart attack, stroke, or hospitalization for congestive heart failure in the past 3 months
• Participants must not have active cancer within the last 5 years
• Participants must not have uncontrolled high blood pressure
• Participants must not have renal impairment with estimated glomerular filtration rate (eGFR) \<60 milliliter per minute per 1.73 square meter (ml/min/1.73m²)
• Participants must not have a diagnosis of type 1 diabetes
• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (16)

Arizona Liver Health - Chandler

Chandler, Arizona, 85225, United States

Location

Orange County Research Center

Orange, California, 92868, United States

Location

Inland Empire Clinical Trials, LLC

Rialto, California, 92377, United States

Location

Synergy Healthcare LLC

Brandon, Florida, 33511, United States

Location

Accel Research Sites - Maitland

Maitland, Florida, 32751, United States

Location

Evolution Clinical Trials, Inc

Miami, Florida, 33122, United States

Location

Advanced Pharma Clinical Research

Miami, Florida, 33175, United States

Location

Floridian Clinical Research

Miami Lakes, Florida, 33016, United States

Location

Charter Research - Winter Park

Orlando, Florida, 32803, United States

Location

IU Health University Hospital

Indianapolis, Indiana, 46290, United States

Location

Houston Research Institute

Houston, Texas, 77079, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Pinnacle Clinical Research

San Antonio, Texas, 78229, United States

Location

P-One Clinic

Hachiōji, 192-0071, Japan

Location

Clinical Research Hospital Tokyo

Shinjuku-ku, 160-0004, Japan

Location

FDI Clinical Research

San Juan, 00927, Puerto Rico

Location

Related Links

• A Single-Ascending and Repeated Dose Study of LY3849891 in Participants With Nonalcoholic Fatty Liver Disease

MeSH Terms

Conditions

Liver Cirrhosis; Fatty Liver

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2022
• First Posted: May 27, 2022
• Study Start: June 8, 2022
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); US (13); JP (2)