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

Lilly

Status and phase: Enrolling; Phase 1

Conditions: Non-Alcoholic Fatty Liver Disease

Treatments: Drug: Placebo; Drug: LY3849891

Study type: Interventional

Funder types: Industry

Identifiers

NCT05395481

18214

J3W-MC-GZOA (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 176 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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176 participants in 4 patient groups, including a placebo group

LY3849891 (Part A)

Experimental group

Description:

Single ascending doses of LY3849891 administered subcutaneously (SC).

Treatment:

Drug: LY3849891

LY3849891 (Part B)

Experimental group

Description:

Repeated doses of LY3849891 administered SC.

Treatment:

Drug: LY3849891

Placebo (Part A)

Placebo Comparator group

Description:

Placebo administered SC.

Treatment:

Drug: Placebo

Placebo (Part B)

Placebo Comparator group

Description:

Placebo administered SC.

Treatment:

Drug: Placebo