A Single-Ascending and Repeated Dose Study of LY3849891 in Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
- Conditions
- Metabolic Dysfunction-Associated Steatohepatitis (MASH)Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)
- Interventions
- Drug: Placebo
- Registration Number
- NCT05395481
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 176
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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
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Participants must have liver fat content ≥10% in Part A and ≥8% for Part B as determined by MRI-PDFF
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Participants must be carriers of the PNPLA3 I148M allele
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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
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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
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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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LY3849891 (Part A) LY3849891 Single ascending doses of LY3849891 administered subcutaneously (SC) LY3849891 (Part B) LY3849891 Repeated doses of LY3849891 administered SC Placebo (Part A) Placebo Placebo administered SC Placebo (Part B) Placebo Placebo administered SC
- Primary Outcome Measures
Name Time Method 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 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
Part B: Pharmacodynamics (PD): Mean change from baseline on liver inflammation and fibrosis measured by magnetic resonance imaging (MRI) Baseline through 24 weeks PD: Mean change from baseline on liver inflammation and fibrosis content measured by MRI
- Secondary Outcome Measures
Name Time Method Part A: PD: Liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF) Predose through Week 26 Part A: PD: Liver fat content measured by (MRI-PDFF)
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: PK: AUC(0-inf) of LY3849891
Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891 Predose through Week 26 Part A: PK: Cmax of LY3849891
Part A: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891 Predose through Week 26 Part A: PK: Tmax of LY3849891
Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF Predose through Week 24 Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF
Part B: PK: AUC(0-inf) of LY3849891 and its Metabolite Predose through Week 24 Part B: PK: AUC(0-inf) of LY3849891 and its metabolite
Part B: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891 and its metabolite Predose through Week 24 Part B: PK: Cmax of LY3849891 and its metabolite
Part B: PK: Tmax of LY3849891 and its metabolite Predose through Week 24 Part B: PK: Tmax of LY3849891 and its metabolite
Trial Locations
- Locations (16)
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
Floridian Clinical Research
🇺🇸Miami, Florida, United States
Evolution Clinical Trials, Inc
🇺🇸Miami, Florida, United States
Advanced Pharma Clinical Research
🇺🇸Miami, Florida, United States
Charter Research - Winter Park
🇺🇸Orlando, Florida, United States
IU Health University Hospital
🇺🇸Indianapolis, Indiana, United States
Houston Research Institute
🇺🇸Houston, Texas, United States
Clinical Trials of Texas, Inc.
🇺🇸San Antonio, Texas, United States
Pinnacle Clinical Research
🇺🇸San Antonio, Texas, United States
P-One Clinic
🇯🇵Hachioji, Tokyo, Japan
Clinical Research Hospital Tokyo
🇯🇵Shinjuku-ku, Tokyo, Japan
FDI Clinical Research
🇵🇷San Juan, Puerto Rico