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

June 22, 2026 updated by: Eli Lilly and Company

A Single-Ascending and Repeated Subcutaneous Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3849891 in Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Who Have the PNPLA3 I148M Genotype

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
115

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
  • Phone Number: 1-317-615-4559
  • Email: LillyTrials@Lilly.com

Study Contact Backup

Study Locations

  • Japan
      • Hachiōji, Japan, 192-0071
        • P-One Clinic
      • Shinjuku-ku, Japan, 160-0004
        • Clinical Research Hospital Tokyo
  • Puerto Rico
      • San Juan, Puerto Rico, 00927
        • FDI Clinical Research
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85225
        • Arizona Liver Health - Chandler
    • California
      • Orange, California, United States, 92868
        • Orange County Research Center
      • Rialto, California, United States, 92377
        • Inland Empire Clinical Trials, LLC
    • Florida
      • Brandon, Florida, United States, 33511
        • Synergy Healthcare LLC
      • Maitland, Florida, United States, 32751
        • Accel Research Sites - Maitland
      • Miami, Florida, United States, 33175
        • Advanced Pharma Clinical Research
      • Miami, Florida, United States, 33122
        • Evolution Clinical Trials, Inc
      • Miami Lakes, Florida, United States, 33016
        • Floridian Clinical Research
      • Orlando, Florida, United States, 32803
        • Charter Research - Winter Park
    • Indiana
      • Indianapolis, Indiana, United States, 46290
        • IU Health University Hospital
    • Texas
      • Houston, Texas, United States, 77079
        • Houston Research Institute
      • San Antonio, Texas, United States, 78229
        • Clinical Trials of Texas, Inc.
      • San Antonio, Texas, United States, 78229
        • Pinnacle Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo (Part A)
Placebo administered SC
Drug: Placebo
Administered SC
Placebo Comparator: Placebo (Part B)
Placebo administered SC
Drug: Placebo
Administered SC
Experimental: LY3849891 (Part A)
Single ascending doses of LY3849891 administered subcutaneously (SC)
Drug: LY3849891
Administered SC
Experimental: LY3849891 (Part B)
Repeated doses of LY3849891 administered SC
Drug: LY3849891
Administered SC

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: Predose up to 26 weeks post dose
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)
Time Frame: Baseline through 24 weeks
PD: Mean change from baseline on liver inflammation and fibrosis content measured by MRI
Baseline through 24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part A: PD: Liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Time Frame: Predose through Week 26
Part A: PD: Liver fat content measured by (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
Time Frame: Predose through Week 26
Part A: PK: AUC(0-inf) of LY3849891
Predose through Week 26
Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891
Time Frame: Predose through Week 26
Part A: PK: Cmax of LY3849891
Predose through Week 26
Part A: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891
Time Frame: Predose through Week 26
Part A: PK: Tmax of LY3849891
Predose through Week 26
Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF
Time Frame: Predose through Week 24
Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF
Predose through Week 24
Part B: PK: AUC(0-inf) of LY3849891 and its Metabolite
Time Frame: Predose through Week 24
Part B: PK: AUC(0-inf) of LY3849891 and its metabolite
Predose through Week 24
Part B: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891 and its metabolite
Time Frame: Predose through Week 24
Part B: PK: Cmax of LY3849891 and its metabolite
Predose through Week 24
Part B: PK: Tmax of LY3849891 and its metabolite
Time Frame: Predose through Week 24
Part B: PK: Tmax of LY3849891 and its metabolite
Predose through Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eli Lilly and Company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 8, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 12, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 12, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 24, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 24, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 27, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 22, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 18214
  • J3W-MC-GZOA (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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