search
Back to results

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

Primary Purpose

Non-Alcoholic Fatty Liver Disease

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LY3849891
Placebo
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Non-Alcoholic Fatty Liver Disease focused on measuring Non-alcoholic steatohepatitis, Hepatic fibrosis, Biomarkers, Magnetic resonance imaging, Pharmacokinetics, Liver fat

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Inland Empire Clinical Trials, LLCRecruiting
  • Orange County Research CenterRecruiting
  • Accel Research Sites - MaitlandRecruiting
  • Floridian Clinical ResearchRecruiting
  • Advanced Pharma Clinical ResearchRecruiting
  • IU Health University HospitalRecruiting
  • Clinical Trials of Texas, Inc.Recruiting
  • P-One ClinicRecruiting
  • Clinical Research Hospital TokyoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

LY3849891 (Part A)

LY3849891 (Part B)

Placebo (Part A)

Placebo (Part B)

Arm Description

Single ascending doses of LY3849891 administered subcutaneously (SC).

Repeated doses of LY3849891 administered SC.

Placebo administered SC.

Placebo administered SC.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

Part A & B: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891
Part A & B: PK: Cmax of LY3849891
Part A & B: Part A & B: PK: Area Under the Concentration Versus Time Curve (AUC) of LY3849891
Part A & B: PK: AUC of LY3849891
Part A & B: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891
Part A & B: PK: Tmax of LY3849891
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
Part B: PD: Alanine aminotransferase (ALT) measurements at baseline and specified time points
Part B: PD: ALT measurements at baseline and specified time points

Full Information

First Posted
May 24, 2022
Last Updated
October 19, 2023
Sponsor
Eli Lilly and Company
search

1. Study Identification

Unique Protocol Identification Number
NCT05395481
Brief Title
A Single-Ascending and Repeated Dose Study of LY3849891 in Participants With Nonalcoholic Fatty Liver Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 15, 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 8, 2022 (Actual)
Primary Completion Date
November 5, 2024 (Anticipated)
Study Completion Date
November 5, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Fatty Liver Disease
Keywords
Non-alcoholic steatohepatitis, Hepatic fibrosis, Biomarkers, Magnetic resonance imaging, Pharmacokinetics, Liver fat

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
176 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LY3849891 (Part A)
Arm Type
Experimental
Arm Description
Single ascending doses of LY3849891 administered subcutaneously (SC).
Arm Title
LY3849891 (Part B)
Arm Type
Experimental
Arm Description
Repeated doses of LY3849891 administered SC.
Arm Title
Placebo (Part A)
Arm Type
Placebo Comparator
Arm Description
Placebo administered SC.
Arm Title
Placebo (Part B)
Arm Type
Placebo Comparator
Arm Description
Placebo administered SC.
Intervention Type
Drug
Intervention Name(s)
LY3849891
Intervention Description
Administered SC.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered SC.
Primary Outcome Measure Information:
Title
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
Description
A summary of TEAEs and SAEs, regardless of causality, will be reported in the Reported Adverse Events module
Time Frame
Predose up to 26 weeks post dose
Title
Part B: Pharmacodynamics (PD): Relative change from baseline on liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Description
PD: Relative change from baseline on liver fat content measured by MRI-PDFF
Time Frame
Baseline through 12 weeks
Secondary Outcome Measure Information:
Title
Part A & B: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891
Description
Part A & B: PK: Cmax of LY3849891
Time Frame
Predose through Week 26
Title
Part A & B: Part A & B: PK: Area Under the Concentration Versus Time Curve (AUC) of LY3849891
Description
Part A & B: PK: AUC of LY3849891
Time Frame
Predose through Week 26
Title
Part A & B: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891
Description
Part A & B: PK: Tmax of LY3849891
Time Frame
Predose through Week 26
Title
Part A & B: PD: Liver fat content at baseline and specified timepoints measured by MRI-PDFF
Description
Part A & B: PD: Liver fat content at baseline and specified timepoints measured by MRI-PDFF
Time Frame
Predose through Week 26
Title
Part B: PD: Alanine aminotransferase (ALT) measurements at baseline and specified time points
Description
Part B: PD: ALT measurements at baseline and specified time points
Time Frame
Predose through Week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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% 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
Phone
1-317-615-4559
Email
ClinicalTrials.gov@Lilly.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Inland Empire Clinical Trials, LLC
City
Rialto
State/Province
California
ZIP/Postal Code
92377
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zeid Kayali
Facility Name
Orange County Research Center
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
(714) 550-9990
First Name & Middle Initial & Last Name & Degree
JOEL MICHAEL NEUTEL
Facility Name
Accel Research Sites - Maitland
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
407-644-1165
First Name & Middle Initial & Last Name & Degree
Eva Maria Heurich
Facility Name
Floridian Clinical Research
City
Miami
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
305-330-9977
First Name & Middle Initial & Last Name & Degree
William Eduardo Sanchez
Facility Name
Advanced Pharma Clinical Research
City
Miami
State/Province
Florida
ZIP/Postal Code
33147-4040
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kimberly Cruz
Facility Name
IU Health University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46290
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
317-274-3264
First Name & Middle Initial & Last Name & Degree
Niharika Samala
Facility Name
Clinical Trials of Texas, Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
2109490122
First Name & Middle Initial & Last Name & Degree
Douglas Scott Denham
Facility Name
P-One Clinic
City
Hachioji
State/Province
Tokyo
ZIP/Postal Code
192-0071
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kenichi Furihata
Facility Name
Clinical Research Hospital Tokyo
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
162-0053
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hiroyuki Fukase

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://trials.lillytrialguide.com/en-US/trial/7Mr5aA8joiUc52P5C9UXKa
Description
A Single-Ascending and Repeated Dose Study of LY3849891 in Participants With Nonalcoholic Fatty Liver Disease

Learn more about this trial

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

We'll reach out to this number within 24 hrs