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

Nonalcoholic Steatohepatitis Clinical Trial

— SYNERGY-NASH  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04166773
• Other study ID #: 17361
• Secondary ID: I8F-MC-GPHR2019-
• Status: Completed
• Phase: Phase 2
• Start date: November 19, 2019
• Est. completion date: January 10, 2024

Study information

• Verified date: April 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: January 10, 2024
• Est. primary completion date: December 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

• 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)

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• Tirzepatide
Administered SC
• Placebo
Administered SC

Locations

Country	Name	City	State
Belgium	UZ Brussel	Brussels	Bruxelles-Capitale, Région De
Belgium	Antwerp University Hospital	Edegem	Antwerpen
Belgium	UZ Gent	Gent	Oost-Vlaanderen
Belgium	UZ Leuven	Leuven	Vlaams-Brabant
Belgium	AZ Delta vzw	Roeselare	West-Vlaanderen
France	Centre Hospitalier Universitaire d'Angers	Angers	Maine-et-Loire
France	Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren	Limoges	Haute-Vienne
France	Hôpital Saint Antoine	Paris
France	Pitie Salpetriere University Hospital	Paris
France	CHU Bordeaux Haut-Leveque	Pessac	Aquitaine
France	Centre Hospitalier Lyon Sud	Pierre-Bénite	Rhône
France	Groupe Hospitalier Mutualiste Les Portes du Sud	Vénissieux	Rhône-Alpes
Israel	Carmel Hospital	Haifa
Israel	Rambam Health Care Campus	Haifa	HaTsafon
Israel	Hadassah Medical Center	Jerusalem	Yerushalayim
Israel	Shaare Zedek Medical Center	Jerusalem	Yerushalayim
Israel	Galilee Medical Center	Nahariya	HaTsafon
Israel	Sheba Medical Center	Ramat Gan	HaMerkaz
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti Di Foggia	Foggia
Italy	Ospedale Santa Maria Goretti	Latina
Italy	A.O.U. Policlinico Paolo Giaccone	Palermo	Sicilia
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino	Torino
Japan	Tokyo Medical And Dental University Medical Hospital	Bunkyo	Tokyo
Japan	Fukuiken Saiseikai Hospital	Fukui
Japan	Gifu Municipal Hospital	Gifu
Japan	Hirakata kohsai Hospital	Higashi-cho, Hirakata-city	Osaka
Japan	Shimane University Hospital	Izumo	Shimane
Japan	Kumamoto Shinto General Hospital	Kumamoto
Japan	University Hospital,Kyoto Prefectural University of Medicine	Kyoto
Japan	Aichi Medical University Hospital	Nagakute-shi	Aichi-ken
Japan	JADECOM Nara City Hospital	Nara-Shi	Nara-Ken
Japan	Niigata University Medical & Dental Hospital	Niigata
Japan	Saga University Hospital	Saga
Japan	JCHO Hokkaido Hospital	Sapporo-shi	Hokkaido
Japan	Osaka Saiseikai Suita hospital	Suita	Osaka
Japan	Yamagata University Hospital	Yamagata
Japan	National Hospital Organization Yokohama Medical Center	Yokohama	Kanagawa
Japan	Yokohama City University Hospital	Yokohama	Kanagawa
Mexico	Centro de Investigación y Gastroenterología	Cuauhtémoc
Mexico	Phylasis Clinicas Research	Cuautitlan Izcalli	Distrito Federal
Mexico	Grupo Medico Camino Sc	Mexico City	Distrito Federal
Mexico	Christus Muguerza Hospital Sur	Monterrey	Nuevo León
Poland	Synexus Polska Oddzial w Lodzi	Lodz	Lódzkie
Poland	Synexus Polska Sp. z o.o. Oddzial w Warszawie	Warsaw	Mazowieckie
Spain	Instituto de Ciencias Médicas	Alicante
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid	Madrid, Comunidad De
Spain	Clínica Juaneda	Palma de Mallorca	Balears [Baleares]
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE)	Sevilla
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
United Kingdom	Queen Elizabeth Hospital Birmingham	Birmingham	England
United Kingdom	Synexus Midlands Clinical Research Centre	Birmingham
United Kingdom	Synexus Clinical Research Centre - Lancashire	Chorley	Lancashire
United Kingdom	John Radcliffe Hospital	Headington	Oxford
United Kingdom	Synexus North East Clinical Research Centre	Hexham	England
United Kingdom	Aintree University Hospital NHS Foundation Trust	Liverpool
United Kingdom	Imperial College London - St Mary's Hospital	London	Westminster
United Kingdom	King's College Hospital	London	London, City Of
United Kingdom	Royal London Hospital	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	Synexus Manchester Clinical Research Centre	Manchester
United Kingdom	Queen's Medical Centre, Nottingham University Hospitals	Nottingham	Nottinghamshire
United Kingdom	Synexus North Teesside Clinical Research Centre	Stockton on Tees	Stockton-on-Tees
United States	The National Diabetes & Obesity Research Institute	Biloxi	Mississippi
United States	University of Alabama-The Kirklin Clinic	Birmingham	Alabama
United States	Excel Medical Clinical Trials	Boca Raton	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	Buffalo Clinical and Translational Research Center	Buffalo	New York
United States	Synexus Clinical Research US, Inc.	Chandler	Arizona
United States	WR-Clinsearch, LLC	Chattanooga	Tennessee
United States	Synexus Clinical Research	Chicago	Illinois
United States	Alliance for Multispecialty Research, LLC	Coral Gables	Florida
United States	Dallas Diabetes Research Center	Dallas	Texas
United States	Liver Center of Texas, PLLC	Dallas	Texas
United States	Radiant Research - Dallas North	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Texoma Medical Center	Denison	Texas
United States	Fresno Clinical Research Center	Fresno	California
United States	Research Centers of America ( Hollywood )	Hollywood	Florida
United States	National Research Institute - Huntington Park	Huntington Park	California
United States	Indiana University Health Hospital	Indianapolis	Indiana
United States	Southern Therapy and Advanced Research (STAR) LLC	Jackson	Mississippi
United States	East Coast Institute for Research, LLC	Jacksonville	Florida
United States	IHS Health Research	Kissimmee	Florida
United States	UCSD - Altman Clinical and Translational Research Institute (ACTRI)	La Jolla	California
United States	National Research Institute - Wilshire	Los Angeles	California
United States	Accel Research Sites - Maitland Clinical Research Unit	Maitland	Florida
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Clinical Pharmacology of Miami	Miami	Florida
United States	Catalina Research Institute, LLC	Montclair	California
United States	Diabetes & Endocrinology Consultants, PC	Morehead City	North Carolina
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Health	New York	New York
United States	Diabetes Medical Center of California	Northridge	California
United States	Synexus Clinical Research US, Inc.	Orlando	Florida
United States	The Center for Digestive Health	Orlando	Florida
United States	Velocity Clinical Research, Panorama City	Panorama City	California
United States	Inland Empire Clinical Trials, LLC	Rialto	California
United States	National Clinical Research, Inc	Richmond	Virginia
United States	Virginia Commonwealth University (VCU) Medical Center	Richmond	Virginia
United States	Texas Diabetes & Endocrinology, P.A.	Round Rock	Texas
United States	American Research Corporation at Texas Liver Institute	San Antonio	Texas
United States	Endeavor Clinical Trials	San Antonio	Texas
United States	Synexus Clinical Research US, Inc.	San Antonio	Texas
United States	Velocity Clinical Research, Santa Ana	Santa Ana	California
United States	Harborview Medical Center/University of Washington	Seattle	Washington
United States	Synexus Clinical Research US, Inc.	The Villages	Florida
United States	Cotton O'Neil Clinical Research Center	Topeka	Kansas
United States	Iowa Diabetes and Endocrinology Research Center	West Des Moines	Iowa
United States	Alliance for Multispecialty Research, LLC	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Belgium,  France,  Israel,  Italy,  Japan,  Mexico,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Absence of NASH with no Worsening of Fibrosis on Liver Histology	Percentage of Participants with Absence of NASH with no Worsening of Fibrosis on Liver Histology	Week 52
Secondary	Percentage of Participants with =1 Point Decrease in Fibrosis Stage with No Worsening of NASH on Liver Histology	Percentage of Participants with =1 Point Decrease in Fibrosis Stage with No Worsening of NASH on Liver Histology	Week 52
Secondary	Percentage of Participants with =1 Point Increase in Fibrosis Stage on Liver Histology	Percentage of Participants with =1 Point Increase in Fibrosis Stage on Liver Histology	Week 52
Secondary	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	Percentage of Participants that Achieve a =2 Point Decrease in NAS on Liver Histology, with =1 Point Reduction in at Least 2 NAS Components	Week 52
Secondary	Mean Absolute Change from Baseline in Liver Fat Content by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)	Mean Absolute Change from Baseline in Liver Fat Content by MRI-PDFF	Baseline, Week 52
Secondary	Mean Change from Baseline in Body Weight	Mean Change from Baseline in Body Weight	Baseline, Week 52

External Links

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