Metabolic Dysfunction-Associated Steatohepatitis (MASH)Phase 1NCT05395481
A Single-Ascending and Repeated Dose Study of LY3849891 in Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
A Phase 1 study testing LY3849891 in people with Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD), run by Eli Lilly and Company at 16 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Metabolic Dysfunction-Associated Steatohepatitis (MASH), Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)
- What is being tested?
- LY3849891
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 115 participants
- Where
- 16 sitesin 3 countries
- Study dates
- 8 Jun 2022to 12 May 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 3 countries.
16 sites in 3 countries
United States13 sites
Synergy Healthcare LLC
Brandon, Florida, 33511
Arizona Liver Health - Chandler
Chandler, Arizona, 85225
Houston Research Institute
Houston, Texas, 77079
IU Health University Hospital
Indianapolis, Indiana, 46290
Accel Research Sites - Maitland
Maitland, Florida, 32751
Evolution Clinical Trials, Inc
Miami, Florida, 33122
Advanced Pharma Clinical Research
Miami, Florida, 33175
Floridian Clinical Research
Miami Lakes, Florida, 33016
Orange County Research Center
Orange, California, 92868
Charter Research - Winter Park
Orlando, Florida, 32803
Inland Empire Clinical Trials, LLC
Rialto, California, 92377
Clinical Trials of Texas, Inc.
San Antonio, Texas, 78229
Pinnacle Clinical Research
San Antonio, Texas, 78229
Japan2 sites
P-One Clinic
Hachiōji, 192-0071
Clinical Research Hospital Tokyo
Shinjuku-ku, 160-0004
About this study
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
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.
- Conditions
- Metabolic Dysfunction-Associated Steatohepatitis (MASH), Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)
- Being tested
- LY3849891, Placebo
- Keywords
- Hepatic fibrosis, Biomarkers, Magnetic resonance imaging, Pharmacokinetics, Liver fat
- Medical subject headings
- Liver Cirrhosis, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3849891Drug
Administered SC
PlaceboDrug
Administered SC
| Study group | Role | What they receive |
|---|---|---|
| LY3849891 (Part A) | Experimental | Single ascending doses of LY3849891 administered subcutaneously (SC) Receives: Drug: LY3849891 |
| LY3849891 (Part B) | Experimental | Repeated doses of LY3849891 administered SC Receives: Drug: LY3849891 |
| Placebo (Part A) | Placebo comparator | Placebo administered SC Receives: Drug: Placebo |
| Placebo (Part B) | Placebo comparator | Placebo administered SC Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
A summary of TEAEs and AEs, regardless of causality, will be reported in the Reported Adverse Events module
Measured: Predose up to 26 weeks post dose
Part B: Pharmacodynamics (PD): Mean change from baseline on liver inflammation and fibrosis measured by magnetic resonance imaging (MRI)
PD: Mean change from baseline on liver inflammation and fibrosis content measured by MRI
Measured: Baseline through 24 weeks
Secondary outcomes (8)
Part A: PD: Liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Part A: PD: Liver fat content measured by (MRI-PDFF)
Measured: Predose through Week 26
Part A: PK: Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC(0-inf)) of LY3849891
Part A: PK: AUC(0-inf) of LY3849891
Measured: Predose through Week 26
Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891
Part A: PK: Cmax of LY3849891
Measured: Predose through Week 26
Part A: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891
Part A: PK: Tmax of LY3849891
Measured: Predose through Week 26
Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF
Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF
Measured: Predose through Week 24
Part B: PK: AUC(0-inf) of LY3849891 and its Metabolite
Part B: PK: AUC(0-inf) of LY3849891 and its metabolite
Measured: Predose through Week 24
Part B: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891 and its metabolite
Part B: PK: Cmax of LY3849891 and its metabolite
Measured: Predose through Week 24
Part B: PK: Tmax of LY3849891 and its metabolite
Part B: PK: Tmax of LY3849891 and its metabolite
Measured: Predose through Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2022
- Study start8 Jun 2022
- Primary completion12 May 2026
- Study completion12 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic Dysfunction-Associated Steatohepatitis (MASH)Studies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 115 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05395481
- Sponsor's protocol ID
- 18214
- Other IDs
- J3W-MC-GZOA
- Status last verified
- Jun 2026
- First submitted
- 24 May 2022
- Last updated
- 24 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05395481
- Acronym / sponsor ID
- 18214
- Conditions
- Metabolic Dysfunction-Associated Steatohepatitis (MASH), Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)
- Keywords
- Hepatic fibrosis, Biomarkers, Magnetic resonance imaging, Pharmacokinetics, Liver fat
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 115 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 8 Jun 2022 (actual)
- Primary completion
- 12 May 2026 (actual)
- Study completion
- 12 May 2026 (actual)
- First posted
- 27 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| LY3849891 (Part A) | Experimental | Drug: LY3849891Single ascending doses of LY3849891 administered subcutaneously (SC) |
| LY3849891 (Part B) | Experimental | Drug: LY3849891Repeated doses of LY3849891 administered SC |
| Placebo (Part A) | Placebo comparator | Drug: PlaceboPlacebo administered SC |
| Placebo (Part B) | Placebo comparator | Drug: PlaceboPlacebo administered SC |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LY3849891Administered SC | Drug | LY3849891 (Part A), LY3849891 (Part B) |
| PlaceboAdministered SC | Drug | Placebo (Part A), Placebo (Part B) |
Primary outcome
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
Time frame: 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)
Time frame: Baseline through 24 weeks
PD: Mean change from baseline on liver inflammation and fibrosis content measured by MRI
8 secondary outcomes
Part A: PD: Liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Time frame: Predose through Week 26
Part A: PK: Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC(0-inf)) of LY3849891
Time frame: Predose through Week 26
Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891
Time frame: Predose through Week 26
Part A: PK: Time to Maximum Observed Concentration (Tmax) of LY3849891
Time frame: Predose through Week 26
Part B: PD: Liver fat content changes at baseline and specified timepoints by MRI-PDFF
Time frame: Predose through Week 24
Part B: PK: AUC(0-inf) of LY3849891 and its Metabolite
Time frame: Predose through Week 24
Part B: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3849891 and its metabolite
Time frame: Predose through Week 24
Part B: PK: Tmax of LY3849891 and its metabolite
Time frame: Predose through Week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
- A Single-Ascending and Repeated Dose Study of LY3849891 in Participants With Nonalcoholic Fatty Liver DiseaseLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
16 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LY3849891 in people with Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD), run by Eli Lilly and Company at 16 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Japan, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Predose up to 26 weeks post dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026.