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Completed

NCT Number: NCT05395481

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

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.

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Key information

Conditions

Metabolic Dysfunction-Associated Steatohepatitis (MASH) Digestive System Diseases Fatty Liver Fibrosis Liver Cirrhosis Liver Diseases Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

P-One Clinic, Hachiōji, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

LY3849891

Drug

Administered SC

Placebo

Drug

Administered SC

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. 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)

  2. 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

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

    Time frame: Predose through Week 26

    Part A: PK: Cmax of LY3849891

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

    Time frame: Predose through Week 26

    Part A: PK: Tmax of LY3849891

  5. 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

  6. 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

  7. 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

  8. Part B: PK: Tmax of LY3849891 and its metabolite

    Time frame: Predose through Week 24

    Part B: PK: Tmax of LY3849891 and its metabolite

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
May 27, 2022
Registry last updated
Jun 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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