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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
176
Administered SC
Administered SC
Arizona Liver Health - Chandler
Chandler, Arizona, United States
Orange County Research Center
Orange, California, United States
Inland Empire Clinical Trials, LLC
Rialto, California, United States
Synergy Healthcare LLC
Brandon, Florida, United States
Accel Research Sites - Maitland
Maitland, Florida, United States
Evolution Clinical Trials, Inc
Miami, Florida, United States
Advanced Pharma Clinical Research
Miami, Florida, United States
Floridian Clinical Research
Miami Lakes, Florida, United States
Charter Research - Winter Park
Orlando, Florida, United States
IU Health University Hospital
Indianapolis, Indiana, United States
...and 6 more locations
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
Time frame: 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
Time frame: Baseline through 24 weeks
Part A: PD: Liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Part A: PD: Liver fat content measured by (MRI-PDFF)
Time frame: Predose through Week 26
Part A: PK: Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC(0-inf)) of LY3849891
Part A: PK: AUC(0-inf) of LY3849891
Time frame: Predose through Week 26
Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891
Part A: PK: Cmax of LY3849891
Time frame: Predose through Week 26
Part A: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891
Part A: PK: Tmax of LY3849891
Time frame: Predose through Week 26
Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF
Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF
Time frame: Predose through Week 24
Part B: PK: AUC(0-inf) of LY3849891 and its Metabolite
Part B: PK: AUC(0-inf) of LY3849891 and its metabolite
Time frame: Predose through Week 24
Part B: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891 and its metabolite
Part B: PK: Cmax of LY3849891 and its metabolite
Time frame: Predose through Week 24
Part B: PK: Tmax of LY3849891 and its metabolite
Part B: PK: Tmax of LY3849891 and its metabolite
Time frame: Predose through Week 24
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