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

NCT04166773 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 17361I8F-MC-GPHR2019-001550-26
• Study Type: interventional
• Target: 190
• Locations: 10 countries
• Sites: 112

Brief 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).

Conditions

Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (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.

  Week 52

Secondary Outcomes (5)

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

  Week 52

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

  Week 52

• 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

  Week 52

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

  Baseline to Week 52

• Mean Change From Baseline in Body Weight

  Baseline to Week 52

Study Arms (4)

5 mg Tirzepatide

EXPERIMENTAL

5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

Drug: Tirzepatide

10 mg Tirzepatide

EXPERIMENTAL

10 mg tirzepatide administered SC once a week.

Drug: Tirzepatide

15 mg Tirzepatide

EXPERIMENTAL

15 mg tirzepatide administered SC once a week.

Drug: Tirzepatide

Placebo

PLACEBO COMPARATOR

Placebo administered SC once a week.

Drug: Placebo

Interventions

Tirzepatide DRUG

Administered SC

Also known as: LY3298176

10 mg Tirzepatide; 15 mg Tirzepatide; 5 mg Tirzepatide

Placebo DRUG

Administered SC

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

* 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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (112)

University of Alabama-The Kirklin Clinic

Birmingham, Alabama, 35205, United States

Location

Synexus Clinical Research US, Inc.

Chandler, Arizona, 85224, United States

Location

Fresno Clinical Research Center

Fresno, California, 93720, United States

Location

National Research Institute - Huntington Park

Huntington Park, California, 90255, United States

Location

UCSD - Altman Clinical and Translational Research Institute (ACTRI)

La Jolla, California, 92037, United States

Location

National Research Institute - Wilshire

Los Angeles, California, 90057, United States

Location

Catalina Research Institute, LLC

Montclair, California, 91763, United States

Location

Diabetes Medical Center of California

Northridge, California, 91325, United States

Location

Velocity Clinical Research, Panorama City

Panorama City, California, 91402, United States

Location

Inland Empire Clinical Trials, LLC

Rialto, California, 92377, United States

Location

Velocity Clinical Research, Santa Ana

Santa Ana, California, 92704, United States

Location

Excel Medical Clinical Trials

Boca Raton, Florida, 33434, United States

Location

Alliance for Multispecialty Research, LLC

Coral Gables, Florida, 33134, United States

Location

Research Centers of America ( Hollywood )

Hollywood, Florida, 33024, United States

Location

East Coast Institute for Research, LLC

Jacksonville, Florida, 32204, United States

Location

IHS Health Research

Kissimmee, Florida, 34741, United States

Location

Accel Research Sites - Maitland Clinical Research Unit

Maitland, Florida, 32751, United States

Location

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

The Center for Digestive Health

Orlando, Florida, 32803, United States

Location

Synexus Clinical Research US, Inc.

Orlando, Florida, 32806, United States

Location

Synexus Clinical Research US, Inc.

The Villages, Florida, 32162, United States

Location

Synexus Clinical Research

Chicago, Illinois, 60602, United States

Location

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Iowa Diabetes and Endocrinology Research Center

West Des Moines, Iowa, 50265, United States

Location

Cotton O'Neil Clinical Research Center

Topeka, Kansas, 66606, United States

Location

Alliance for Multispecialty Research, LLC

Wichita, Kansas, 67207, United States

Location

Tandem Clinical Research

Marrero, Louisiana, 70072, United States

Location

The National Diabetes & Obesity Research Institute

Biloxi, Mississippi, 39532, United States

Location

Southern Therapy and Advanced Research (STAR) LLC

Jackson, Mississippi, 39216, United States

Location

Buffalo Clinical and Translational Research Center

Buffalo, New York, 14203, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Diabetes & Endocrinology Consultants, PC

Morehead City, North Carolina, 28557, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

WR-Clinsearch, LLC

Chattanooga, Tennessee, 37421, United States

Location

Dallas Diabetes Research Center

Dallas, Texas, 75230, United States

Location

Radiant Research - Dallas North

Dallas, Texas, 75231, United States

Location

Liver Center of Texas, PLLC

Dallas, Texas, 75234-7858, United States

Location

Texoma Medical Center

Denison, Texas, 75020, United States

Location

Texas Diabetes & Endocrinology, P.A.

Round Rock, Texas, 78681, United States

Location

American Research Corporation at Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Synexus Clinical Research US, Inc.

San Antonio, Texas, 78229, United States

Location

Endeavor Clinical Trials

San Antonio, Texas, 78240, United States

Location

National Clinical Research, Inc

Richmond, Virginia, 23294, United States

Location

Virginia Commonwealth University (VCU) Medical Center

Richmond, Virginia, 23298, United States

Location

Harborview Medical Center/University of Washington

Seattle, Washington, 98104, United States

Location

Antwerp University Hospital

Edegem, Antwerpen, 2650, Belgium

Location

UZ Brussel

Brussels, Bruxelles-Capitale, Région de, 1090, Belgium

Location

UZ Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

AZ Delta vzw

Roeselare, West-Vlaanderen, 8800, Belgium

Location

CHU Bordeaux Haut-Leveque

Pessac, Aquitaine, 33600, France

Location

Groupe Hospitalier Mutualiste Les Portes du Sud

Vénissieux, Auvergne-Rhône-Alpes, 69200, France

Location

Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren

Limoges, Haute-Vienne, 87042, France

Location

Centre Hospitalier Universitaire d'Angers

Angers, Maine-et-Loire, 49933, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Rhône, 69494 Cédex, France

Location

Pitie Salpetriere University Hospital

Paris, 75013, France

Location

Hôpital Saint Antoine

Paris, 75571, France

Location

Sheba Medical Center

Ramat Gan, Central District, 5265601, Israel

Location

Hadassah Medical Center

Jerusalem, Jerusalem, 9112001, Israel

Location

Shaare Zedek Medical Center

Jerusalem, Jerusalem, 9778419, Israel

Location

Rambam Health Care Campus

Haifa, Northern District, 3109601, Israel

Location

Galilee Medical Center

Nahariya, Northern District, 2210001, Israel

Location

Carmel Hospital

Haifa, 3436212, Israel

Location

A.O.U. Policlinico Paolo Giaccone

Palermo, Sicily, 90127, Italy

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti Di Foggia

Foggia, 71100, Italy

Location

Ospedale Santa Maria Goretti

Latina, 04100, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

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

Torino, 10126, Italy

Location

Aichi Medical University Hospital

Nagakute-shi, Aichi-ken, 480-1195, Japan

Location

JCHO Hokkaido Hospital

Sapporo, Hokkaido, 062-8618, Japan

Location

Yokohama City University Hospital

Yokohama, Kanagawa, 236-0004, Japan

Location

National Hospital Organization Yokohama Medical Center

Yokohama, Kanagawa, 2458575, Japan

Location

JADECOM Nara City Hospital

Nara, Nara, 630-8305, Japan

Location

Hirakata kohsai Hospital

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

Location

Osaka Saiseikai Suita hospital

Suita, Osaka, 564-0013, Japan

Location

Shimane University Hospital

Izumo, Shimane, 693-0021, Japan

Location

Tokyo Medical And Dental University Medical Hospital

Bunkyō, Tokyo, 113-8519, Japan

Location

Fukuiken Saiseikai Hospital

Fukui, 918-8503, Japan

Location

Gifu Municipal Hospital

Gifu, 500-8323, Japan

Location

Kumamoto Shinto General Hospital

Kumamoto, 862-8655, Japan

Location

University Hospital,Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Niigata University Medical & Dental Hospital

Niigata, 951-8520, Japan

Location

Saga University Hospital

Saga, 849-8501, Japan

Location

Yamagata University Hospital

Yamagata, 990-9585, Japan

Location

Phylasis Clinicas Research

Cuautitlan Izcalli, Mexico City, 54769, Mexico

Location

Grupo Medico Camino Sc

Mexico City, Mexico City, 3310, Mexico

Location

Christus Muguerza Hospital Sur

Monterrey, Nuevo León, 64988, Mexico

Location

Centro de Investigación y Gastroenterología

Cuauhtémoc, 6700, Mexico

Location

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

Warsaw, Masovian Voivodeship, 02-672, Poland

Location

Synexus Polska Oddział w Lodzi

Lodz, Łódź Voivodeship, 90-127, Poland

Location

Clínica Juaneda

Palma de Mallorca, Balears [Baleares], 7014, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Comunidad de, 28034, Spain

Location

Instituto de Ciencias Médicas

Alicante, 3004, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, 28222, Spain

Location

Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE)

Seville, 41003, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Queen Elizabeth Hospital Birmingham

Birmingham, England, B15 2TH, United Kingdom

Location

Synexus North East Clinical Research Centre

Hexham, England, NE46 1QJ, United Kingdom

Location

Royal London Hospital

London, England, E1 1BB, United Kingdom

Location

St. George's Hospital

London, England, SW17 0QT, United Kingdom

Location

Synexus Clinical Research Centre - Lancashire

Chorley, Lancashire, PR7 7NA, United Kingdom

Location

King's College Hospital

London, London, City of, SE5 9RL, United Kingdom

Location

Queen's Medical Centre, Nottingham University Hospitals

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

John Radcliffe Hospital

Headington, Oxford, OX3 9DU, United Kingdom

Location

Synexus North Teesside Clinical Research Centre

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

Location

Imperial College London - St Mary's Hospital

London, Westminster, W2 1NY, United Kingdom

Location

Synexus Midlands Clinical Research Centre

Birmingham, B15 2SQ, United Kingdom

Location

Aintree University Hospital NHS Foundation Trust

Liverpool, L9 7AL, United Kingdom

Location

Synexus Manchester Clinical Research Centre

Manchester, M15 6SX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38856224 DERIVED

Related Links

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

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2019
• First Posted: November 18, 2019
• Study Start: November 19, 2019
• Primary Completion: December 11, 2023
• Study Completion: January 10, 2024
• Last Updated: January 24, 2025
• Results First Posted: January 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

BE (5); PL (2); IT (5); ES (7); ME (4); IL (6); US (47); GB (13); FR (7); JP (16)