A Single-Ascending and Repeated Dose Study of LY3849891 in Participants With Nonalcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease Clinical Trial

Official title:

A Single-Ascending and Repeated Subcutaneous Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3849891 in Participants With Nonalcoholic Fatty Liver Disease Who Have the PNPLA3 I148M Genotype

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05395481
• Other study ID #: 18214
• Secondary ID: J3W-MC-GZOA
• Status: Recruiting
• Phase: Phase 1
• Start date: June 8, 2022
• Est. completion date: November 5, 2024

Study information

• Verified date: March 2024
• Source: Eli Lilly and Company
• Contact: There may be multiple sites in this clinical trial. 1-877-CTLILL
• Phone: 1-317-615-4559
• Email: ClinicalTrials.gov[@]Lilly.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the safety and tolerability of the study drug LY3849891 in participants with nonalcoholic fatty liver disease 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 fatty liver disease. 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 and 13 visits in parts A and B, respectively.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 176
• Est. completion date: November 5, 2024
• Est. primary completion date: November 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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% 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%
• Male participants agree to use an effective method of contraception for the duration of the study
• 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 milliters/minute/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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-Alcoholic Fatty Liver Disease

Intervention

Drug:
• LY3849891
Administered SC.
• Placebo
Administered SC.

Locations

Country	Name	City	State
Japan	P-One Clinic	Hachioji	Tokyo
Japan	Clinical Research Hospital Tokyo	Shinjuku-ku	Tokyo
United States	IU Health University Hospital	Indianapolis	Indiana
United States	Accel Research Sites - Maitland	Maitland	Florida
United States	Advanced Pharma Clinical Research	Miami	Florida
United States	Floridian Clinical Research	Miami	Florida
United States	Inland Empire Clinical Trials, LLC	Rialto	California
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Pinnacle Clinical Research	San Antonio	Texas
United States	Orange County Research Center	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	A summary of TEAEs and SAEs, regardless of causality, will be reported in the Reported Adverse Events module	Predose up to 26 weeks post dose
Primary	Part B: Pharmacodynamics (PD): Relative change from baseline on liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF)	PD: Relative change from baseline on liver fat content measured by MRI-PDFF	Baseline through 12 weeks
Secondary	Part A & B: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891	Part A & B: PK: Cmax of LY3849891	Predose through Week 26
Secondary	Part A & B: Part A & B: PK: Area Under the Concentration Versus Time Curve (AUC) of LY3849891	Part A & B: PK: AUC of LY3849891	Predose through Week 26
Secondary	Part A & B: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891	Part A & B: PK: Tmax of LY3849891	Predose through Week 26
Secondary	Part A & B: PD: Liver fat content at baseline and specified timepoints measured by MRI-PDFF	Part A & B: PD: Liver fat content at baseline and specified timepoints measured by MRI-PDFF	Predose through Week 26
Secondary	Part B: PD: Alanine aminotransferase (ALT) measurements at baseline and specified time points	Part B: PD: ALT measurements at baseline and specified time points	Predose through Week 26

External Links

•   A Single-Ascending and Repeated Dose Study of LY3849891 in Participants With Nonalcoholic Fatty Liver Disease