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Nonalcoholic SteatohepatitisPhase 2SYNERGY-NASHNCT04166773

A Study of Tirzepatide (LY3298176) in Participants With Nonalcoholic Steatohepatitis (NASH)

A Phase 2 study testing Tirzepatide in people with Nonalcoholic Steatohepatitis, run by Eli Lilly and Company at 112 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to see if the study drug, tirzepatide administered once weekly, is safe and effective as a treatment for Nonalcoholic Steatohepatitis (NASH). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Nonalcoholic Steatohepatitis
What is being tested?
Tirzepatide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
190 participants
Where
112 sitesin 10 countries
Study dates
19 Nov 2019to 10 Jan 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult
  • Participants must have a body mass index (BMI) ≥27 kilograms per square meter (kg/m²) and ≤50 kg/m² with stable body weight for at least 3 months
  • Participants with or without type 2 diabetes mellitus (T2DM)
  • If with T2DM, hemoglobin A1c (HbA1c) ≤9.5%
  • Participants must be willing to undergo baseline and endpoint liver biopsies
  • Participants must have histologic diagnosis of NASH with stage 2 or 3 fibrosis by liver biopsy
  • 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 6 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) <30 milliters/minute/1.73m²; for participants on metformin, eGFR <45 mL/min/1.73m²
  • Participants must not have a diagnosis of type 1 diabetes
  • Participants must not have a history of pancreatitis (acute or chronic)
  • Participants must not have calcitonin ≥35 nanograms per liter
  • Participant must not have family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma (family is defined as a first degree relative)
  • Female participants must not be pregnant, breast-feeding, or intend to become pregnant or of childbearing potential and not using adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice)

Trial locations and contacts

112 sites in 10 countries.

112 sites in 10 countries

United States47 sites

  • The National Diabetes & Obesity Research Institute

    Biloxi, Mississippi, 39532

  • University of Alabama-The Kirklin Clinic

    Birmingham, Alabama, 35205

  • Excel Medical Clinical Trials

    Boca Raton, Florida, 33434

  • Buffalo Clinical and Translational Research Center

    Buffalo, New York, 14203

  • Synexus Clinical Research US, Inc.

    Chandler, Arizona, 85224

  • WR-Clinsearch, LLC

    Chattanooga, Tennessee, 37421

  • Synexus Clinical Research

    Chicago, Illinois, 60602

  • Alliance for Multispecialty Research, LLC

    Coral Gables, Florida, 33134

  • Dallas Diabetes Research Center

    Dallas, Texas, 75230

  • Radiant Research - Dallas North

    Dallas, Texas, 75231

  • Liver Center of Texas, PLLC

    Dallas, Texas, 75234-7858

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Texoma Medical Center

    Denison, Texas, 75020

  • Fresno Clinical Research Center

    Fresno, California, 93720

  • Research Centers of America ( Hollywood )

    Hollywood, Florida, 33024

  • National Research Institute - Huntington Park

    Huntington Park, California, 90255

  • Indiana University Health Hospital

    Indianapolis, Indiana, 46202

  • Southern Therapy and Advanced Research (STAR) LLC

    Jackson, Mississippi, 39216

  • East Coast Institute for Research, LLC

    Jacksonville, Florida, 32204

  • IHS Health Research

    Kissimmee, Florida, 34741

  • UCSD - Altman Clinical and Translational Research Institute (ACTRI)

    La Jolla, California, 92037

  • National Research Institute - Wilshire

    Los Angeles, California, 90057

  • Accel Research Sites - Maitland Clinical Research Unit

    Maitland, Florida, 32751

  • Tandem Clinical Research

    Marrero, Louisiana, 70072

  • Clinical Pharmacology of Miami

    Miami, Florida, 33014

  • Catalina Research Institute, LLC

    Montclair, California, 91763

  • Diabetes & Endocrinology Consultants, PC

    Morehead City, North Carolina, 28557

  • NYU Langone Health

    New York, New York, 10016

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Diabetes Medical Center of California

    Northridge, California, 91325

  • The Center for Digestive Health

    Orlando, Florida, 32803

  • Synexus Clinical Research US, Inc.

    Orlando, Florida, 32806

  • Velocity Clinical Research, Panorama City

    Panorama City, California, 91402

  • Inland Empire Clinical Trials, LLC

    Rialto, California, 92377

  • National Clinical Research, Inc

    Richmond, Virginia, 23294

  • Virginia Commonwealth University (VCU) Medical Center

    Richmond, Virginia, 23298

  • Texas Diabetes & Endocrinology, P.A.

    Round Rock, Texas, 78681

  • American Research Corporation at Texas Liver Institute

    San Antonio, Texas, 78215

  • Synexus Clinical Research US, Inc.

    San Antonio, Texas, 78229

  • Endeavor Clinical Trials

    San Antonio, Texas, 78240

  • Velocity Clinical Research, Santa Ana

    Santa Ana, California, 92704

  • Harborview Medical Center/University of Washington

    Seattle, Washington, 98104

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Synexus Clinical Research US, Inc.

    The Villages, Florida, 32162

  • Cotton O'Neil Clinical Research Center

    Topeka, Kansas, 66606

  • Iowa Diabetes and Endocrinology Research Center

    West Des Moines, Iowa, 50265

  • Alliance for Multispecialty Research, LLC

    Wichita, Kansas, 67207

Other trials in United States

Japan16 sites

  • Tokyo Medical And Dental University Medical Hospital

    Bunkyō, Tokyo, 113-8519

  • Fukuiken Saiseikai Hospital

    Fukui, 918-8503

  • Gifu Municipal Hospital

    Gifu, 500-8323

  • Hirakata kohsai Hospital

    Higashi-cho, Hirakata-city, Osaka, 573-0153

  • Shimane University Hospital

    Izumo, Shimane, 693-0021

  • Kumamoto Shinto General Hospital

    Kumamoto, 862-8655

  • University Hospital,Kyoto Prefectural University of Medicine

    Kyoto, 602-8566

  • Aichi Medical University Hospital

    Nagakute-shi, Aichi-ken, 480-1195

  • JADECOM Nara City Hospital

    Nara, Nara, 630-8305

  • Niigata University Medical & Dental Hospital

    Niigata, 951-8520

  • Saga University Hospital

    Saga, 849-8501

  • JCHO Hokkaido Hospital

    Sapporo, Hokkaido, 062-8618

  • Osaka Saiseikai Suita hospital

    Suita, Osaka, 564-0013

  • Yamagata University Hospital

    Yamagata, 990-9585

  • Yokohama City University Hospital

    Yokohama, Kanagawa, 236-0004

  • National Hospital Organization Yokohama Medical Center

    Yokohama, Kanagawa, 2458575

Other trials in Japan

United Kingdom13 sites

  • Queen Elizabeth Hospital Birmingham

    Birmingham, England, B15 2TH

  • Synexus Midlands Clinical Research Centre

    Birmingham, B15 2SQ

  • Synexus Clinical Research Centre - Lancashire

    Chorley, Lancashire, PR7 7NA

  • John Radcliffe Hospital

    Headington, Oxford, OX3 9DU

  • Synexus North East Clinical Research Centre

    Hexham, England, NE46 1QJ

  • Aintree University Hospital NHS Foundation Trust

    Liverpool, L9 7AL

  • Royal London Hospital

    London, England, E1 1BB

  • St. George's Hospital

    London, England, SW17 0QT

  • King's College Hospital

    London, London, City of, SE5 9RL

  • Imperial College London - St Mary's Hospital

    London, Westminster, W2 1NY

  • Synexus Manchester Clinical Research Centre

    Manchester, M15 6SX

  • Queen's Medical Centre, Nottingham University Hospitals

    Nottingham, Nottinghamshire, NG7 2UH

  • Synexus North Teesside Clinical Research Centre

    Stockton-on-Tees, Stockton-on-Tees, TS19 8PE

Other trials in United Kingdom

France7 sites

  • Centre Hospitalier Universitaire d'Angers

    Angers, Maine-et-Loire, 49933

  • Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren

    Limoges, Haute-Vienne, 87042

  • Pitie Salpetriere University Hospital

    Paris, 75013

  • Hôpital Saint Antoine

    Paris, 75571

  • CHU Bordeaux Haut-Leveque

    Pessac, Aquitaine, 33600

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, Rhône, 69494 Cédex

  • Groupe Hospitalier Mutualiste Les Portes du Sud

    Vénissieux, Auvergne-Rhône-Alpes, 69200

Other trials in France

Spain7 sites

  • Instituto de Ciencias Médicas

    Alicante, 3004

  • Hospital Universitario Ramón y Cajal

    Madrid, Madrid, Comunidad de, 28034

  • Hospital Universitario Puerta de Hierro Majadahonda

    Madrid, 28222

  • Clínica Juaneda

    Palma de Mallorca, Balears [Baleares], 7014

  • Hospital Universitario Marqués de Valdecilla

    Santander, Cantabria, 39008

  • Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE)

    Seville, 41003

  • Hospital Universitario Virgen Del Rocio

    Seville, 41013

Other trials in Spain

Israel6 sites

  • Rambam Health Care Campus

    Haifa, Northern District, 3109601

  • Carmel Hospital

    Haifa, 3436212

  • Hadassah Medical Center

    Jerusalem, Jerusalem, 9112001

  • Shaare Zedek Medical Center

    Jerusalem, Jerusalem, 9778419

  • Galilee Medical Center

    Nahariya, Northern District, 2210001

  • Sheba Medical Center

    Ramat Gan, Central District, 5265601

Other trials in Israel

Belgium5 sites

  • UZ Brussel

    Brussels, Bruxelles-Capitale, Région de, 1090

  • Antwerp University Hospital

    Edegem, Antwerpen, 2650

  • UZ Gent

    Ghent, Oost-Vlaanderen, 9000

  • UZ Leuven

    Leuven, Vlaams-Brabant, 3000

  • AZ Delta vzw

    Roeselare, West-Vlaanderen, 8800

Other trials in Belgium

Italy5 sites

  • Azienda Ospedaliero Universitaria Ospedali Riuniti Di Foggia

    Foggia, 71100

  • Ospedale Santa Maria Goretti

    Latina, 04100

  • A.O.U. Policlinico Paolo Giaccone

    Palermo, Sicily, 90127

  • Fondazione Policlinico Universitario Agostino Gemelli

    Roma, 00168

  • Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino

    Torino, 10126

Other trials in Italy

Mexico4 sites

  • Centro de Investigación y Gastroenterología

    Cuauhtémoc, 6700

  • Phylasis Clinicas Research

    Cuautitlan Izcalli, Mexico City, 54769

  • Grupo Medico Camino Sc

    Mexico City, Mexico City, 3310

  • Christus Muguerza Hospital Sur

    Monterrey, Nuevo León, 64988

Other trials in Mexico

Poland2 sites

  • Synexus Polska Oddział w Lodzi

    Lodz, Łódź Voivodeship, 90-127

  • Synexus Polska Sp. z o.o. Oddzial w Warszawie

    Warsaw, Masovian Voivodeship, 02-672

Other trials in Poland

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Comparing the Efficacy and Safety of Tirzepatide Versus Placebo in Patients With Nonalcoholic Steatohepatitis (NASH)

The purpose of this study is to see if the study drug, tirzepatide administered once weekly, is safe and effective as a treatment for Nonalcoholic Steatohepatitis (NASH).

Being tested
Tirzepatide, Placebo
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TirzepatideDrug

    Also called LY3298176

    Administered SC

  • PlaceboDrug

    Administered SC

Study groups in NCT04166773
Study groupRoleWhat they receive
5 mg TirzepatideExperimental5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
Receives: Drug: Tirzepatide
10 mg TirzepatideExperimental10 mg tirzepatide administered SC once a week.
Receives: Drug: Tirzepatide
15 mg TirzepatideExperimental15 mg tirzepatide administered SC once a week.
Receives: Drug: Tirzepatide
PlaceboPlacebo comparatorPlacebo administered SC once a week.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Absence of Nonalcoholic Steatohepatitis (NASH) With no Worsening of Fibrosis on Liver Histology

    NASH resolution is defined as the absence of fatty liver disease or simple steatosis without steatohepatitis; the absence of hepatocellular ballooning (nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) 0 for ballooning); with or without mild lobular inflammation (NAS 0 or 1 for inflammation); and any value for steatosis. No worsening of fibrosis is defined as no increase in fibrosis stage from baseline to Week 52.

    Measured: Week 52

Secondary outcomes (5)

  1. Percentage of Participants With ≥1 Point Decrease in Fibrosis Stage With No Worsening of NASH on Liver Histology

    NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Evaluation of fibrosis stage was based on the nonalcoholic steatohepatitis clinical research network (NASH CRN) fibrosis staging system, which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. Participants were evaluated with the NASH CRN scoring system with ≥1-point reduction without worsening of NASH (defined as no increase in the NAS score).

    Measured: Week 52

  2. Percentage of Participants With ≥1 Point Increase in Fibrosis Stage on Liver Histology

    Participants were evaluated with the NASH CRN scoring system with ≥1 stage increase in fibrosis.

    Measured: Week 52

  3. Percentage of Participants That Achieve a ≥2 Point Decrease in NAFLD (Non-alcoholic Fatty Liver Disease) Activity Score (NAS) on Liver Histology, With ≥1 Point Reduction in at Least 2 NAS Components

    Hepatic histological improvement in NAS was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in at least 2 NAS components (lobular inflammation, hepatocellular ballooning or steatosis). The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8, with the higher score indicating more aggressive disease.

    Measured: Week 52

  4. Mean Absolute Change From Baseline in Liver Fat Content by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)

    MRI-PDFF is an established method that enables quantification of fat content in the liver. The value of whole liver fat as assessed by MRI-PDFF is expressed in percentage (%) and ranges from 0 to 100% with higher values representing higher liver fat level. Least square (LS) mean was calculated using mixed model repeated measures (MMRM) model for post-baseline measures: Variable = Baseline + Diabetes Flag (DIABFL) + REGION1 + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Change from Baseline) = Unstructured.

    Measured: Baseline to Week 52

  5. Mean Change From Baseline in Body Weight

    Change in body weight at the end of 52 weeks measured in kilogram (kg) using a calibrated scale. LS mean was calculated using MMRM model for post-baseline measures: Variable = Baseline + DIABFL + REGION1 + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Change from Baseline) = Unstructured.

    Measured: Baseline to Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2019
  2. Study start19 Nov 2019
  3. Primary completion11 Dec 2023
  4. Study completion10 Jan 2024

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
190 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04166773
Sponsor's protocol ID
17361
Other IDs
I8F-MC-GPHR, 2019-001550-26, 2019
Acronym
SYNERGY-NASH
Status last verified
Jan 2025
First submitted
15 Nov 2019
Last updated
24 Jan 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Publications

  • Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J, Bugianesi E, Yoneda M, Behling C, Cummings OW, Tang Y, Brouwers B, Robins DA, Nikooie A, Bunck MC, Haupt A, Sanyal AJ; SYNERGY-NASH Investigators. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. N Engl J Med. 2024 Jul 25;391(4):299-310. doi: 10.1056/NEJMoa2401943. Epub 2024 Jun 8.

    PubMed 38856224

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tirzepatide in people with Nonalcoholic Steatohepatitis, run by Eli Lilly and Company at 112 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 112 sites in United States, Japan, United Kingdom, France, Spain and 5 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With Absence of Nonalcoholic Steatohepatitis (NASH) With no Worsening of Fibrosis on Liver Histology (time frame: Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04166773, which also lists 1 linked publication.

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 Jan 2025.

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