Clinical trial NCT05395481: A Single-Ascending and Repeated Dose Study of LY3849891 in Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metabolic Dysfunction-Associated Steatohepatitis (MASH)
Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)
Keywords: Hepatic fibrosis
Biomarkers
Magnetic resonance imaging
Pharmacokinetics
Liver fat
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2022-05-27
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Predose up to 26 weeks post dose
measure: Part B: Pharmacodynamics (PD): Mean change from baseline on liver inflammation and fibrosis measured by magnetic resonance imaging (MRI)
timeFrame: Baseline through 24 weeks
Secondary outcomes:
measure: Part A: PD: Liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Predose through Week 26
measure: Part A: PK: Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC(0-inf)) of LY3849891
timeFrame: Predose through Week 26
measure: Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891
timeFrame: Predose through Week 26
measure: Part A: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891
timeFrame: Predose through Week 26
measure: Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF
timeFrame: Predose through Week 24
measure: Part B: PK: AUC(0-inf) of LY3849891 and its Metabolite
timeFrame: Predose through Week 24
measure: Part B: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891 and its metabolite
timeFrame: Predose through Week 24
measure: Part B: PK: Tmax of LY3849891 and its metabolite
timeFrame: Predose through Week 24
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Arizona Liver Health - Chandler
state: Arizona
city: Orange
country: United States
facility: Orange County Research Center
state: California
city: Rialto
country: United States
facility: Inland Empire Clinical Trials, LLC
state: California
city: Brandon
country: United States
facility: Synergy Healthcare LLC
state: Florida
city: Maitland
country: United States
facility: Accel Research Sites - Maitland
state: Florida
city: Miami
country: United States
facility: Floridian Clinical Research
state: Florida
city: Miami
country: United States
facility: Evolution Clinical Trials, Inc
state: Florida
city: Miami
country: United States
facility: Advanced Pharma Clinical Research
state: Florida
city: Orlando
country: United States
facility: Charter Research - Winter Park
state: Florida
city: Indianapolis
country: United States
facility: IU Health University Hospital
state: Indiana
city: Houston
country: United States
facility: Houston Research Institute
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Hachioji
country: Japan
facility: P-One Clinic
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Clinical Research Hospital Tokyo
state: Tokyo
city: San Juan
country: Puerto Rico
facility: FDI Clinical Research
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: