History of Changes for Study: NCT04166773

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

A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.

Study Record Versions

Version	Submitted Date	Changes
1	November 15, 2019	None (earliest Version on record)
2	November 22, 2019	References and Study Status
3	December 2, 2019	Recruitment Status, Study Status, Contacts/Locations and Oversight
4	December 16, 2019	Contacts/Locations and Study Status
5	January 2, 2020	Contacts/Locations and Study Status
6	January 16, 2020	Contacts/Locations and Study Status
7	February 4, 2020	Contacts/Locations and Study Status
8	February 19, 2020	Contacts/Locations and Study Status
9	March 2, 2020	Contacts/Locations and Study Status
10	March 16, 2020	Contacts/Locations and Study Status
11	April 21, 2020	Contacts/Locations and Study Status
12	May 4, 2020	Contacts/Locations and Study Status
13	May 18, 2020	Contacts/Locations and Study Status
14	June 4, 2020	Contacts/Locations and Study Status
15	June 17, 2020	Contacts/Locations and Study Status
16	July 2, 2020	Contacts/Locations and Study Status
17	July 6, 2020	Contacts/Locations and Study Status
18	July 17, 2020	Contacts/Locations and Study Status
19	August 3, 2020	Contacts/Locations and Study Status
20	August 17, 2020	Contacts/Locations and Study Status
21	September 2, 2020	Contacts/Locations and Study Status
22	September 16, 2020	Contacts/Locations and Study Status
23	October 2, 2020	Contacts/Locations and Study Status
24	October 16, 2020	Contacts/Locations and Study Status
25	November 3, 2020	Contacts/Locations and Study Status
26	November 17, 2020	Contacts/Locations and Study Status
27	December 3, 2020	Contacts/Locations and Study Status
28	December 17, 2020	Contacts/Locations and Study Status
29	January 6, 2021	Contacts/Locations and Study Status
30	January 8, 2021	References and Study Status
31	January 18, 2021	Contacts/Locations and Study Status
32	February 4, 2021	Contacts/Locations and Study Status
33	February 17, 2021	Contacts/Locations and Study Status
34	March 3, 2021	Contacts/Locations and Study Status
35	March 18, 2021	Contacts/Locations and Study Status
36	April 6, 2021	Contacts/Locations and Study Status
37	April 16, 2021	Contacts/Locations and Study Status
38	May 4, 2021	Contacts/Locations and Study Status
39	May 18, 2021	Contacts/Locations and Study Status
40	June 8, 2021	Contacts/Locations and Study Status
41	June 17, 2021	Contacts/Locations and Study Status
42	July 6, 2021	Contacts/Locations and Study Status
43	July 15, 2021	Study Status
44	August 4, 2021	Study Status
45	August 17, 2021	Study Status and Contacts/Locations
46	September 2, 2021	Contacts/Locations and Study Status
47	September 20, 2021	Contacts/Locations and Study Status
48	October 5, 2021	Contacts/Locations and Study Status
49	October 15, 2021	Contacts/Locations and Study Status
50	November 8, 2021	Contacts/Locations and Study Status
51	November 17, 2021	Contacts/Locations and Study Status
52	December 8, 2021	Contacts/Locations and Study Status
53	December 16, 2021	Contacts/Locations and Study Status
54	January 5, 2022	Study Status and Contacts/Locations
55	January 18, 2022	Contacts/Locations and Study Status
56	February 3, 2022	Contacts/Locations and Study Status
57	February 18, 2022	Contacts/Locations and Study Status
58	March 9, 2022	Contacts/Locations and Study Status
59	March 22, 2022	Contacts/Locations and Study Status
60	April 6, 2022	Study Status and Contacts/Locations
61	April 18, 2022	Contacts/Locations and Study Status
62	May 9, 2022	Contacts/Locations and Study Status
63	May 20, 2022	Contacts/Locations and Study Status
64	June 9, 2022	Contacts/Locations and Study Status
65	June 20, 2022	Contacts/Locations and Study Status
66	July 7, 2022	Study Status and Contacts/Locations
67	July 19, 2022	Contacts/Locations and Study Status
68	August 8, 2022	Study Status
69	August 17, 2022	Contacts/Locations and Study Status
70	September 8, 2022	Contacts/Locations and Study Status
71	October 11, 2022	Contacts/Locations and Study Status
72	October 18, 2022	Contacts/Locations and Study Status
73	November 10, 2022	Contacts/Locations and Study Status
74	November 23, 2022	Contacts/Locations and Study Status
75	December 9, 2022	Contacts/Locations and Study Status
76	December 26, 2022	Contacts/Locations and Study Status
77	January 10, 2023	Contacts/Locations and Study Status
78	January 17, 2023	Recruitment Status, Contacts/Locations and Study Status
79	February 13, 2023	Study Status
80	February 22, 2023	Study Status
81	March 7, 2023	Study Status
82	April 12, 2023	Study Status
83	April 16, 2023	Study Status
84	May 12, 2023	Study Status
85	May 23, 2023	Study Status
86	June 11, 2023	Study Status
87	July 12, 2023	Study Status
88	July 28, 2023	Contacts/Locations and Study Status
89	September 6, 2023	Contacts/Locations and Study Status
90	October 5, 2023	Contacts/Locations and Study Status
91	October 19, 2023	Study Status
92	April 17, 2024	Recruitment Status, Contacts/Locations, Study Status and Study Design

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	17361
Brief Title:	A Study of Tirzepatide (LY3298176) in Participants With Nonalcoholic Steatohepatitis (NASH) (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)
Secondary IDs:	I8F-MC-GPHR [Eli Lilly and Company] 2019-001550-26 [EudraCT Number]

Study Status


Record Verification:	January 2023
Overall Status:	Active, not recruiting
Study Start:	November 19, 2019
Primary Completion:	January 16, 2024 [Anticipated]
Study Completion:	February 13, 2024 [Anticipated]

First Submitted:	November 15, 2019
First Submitted that Met QC Criteria:	November 15, 2019
First Posted:	November 18, 2019 [Actual]

Last Update Submitted that Met QC Criteria:	January 17, 2023
Last Update Posted:	January 18, 2023 [Actual]

Sponsor/Collaborators


Sponsor:	Eli Lilly and Company
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	No

Study Description


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).
Detailed Description:

Conditions


Conditions:	Nonalcoholic Steatohepatitis
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 2
Interventional Study Model:	Parallel Assignment
Number of Arms:	4
Masking:	Double (Participant, Investigator)
Allocation:	Randomized
Enrollment:	196 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: 5 mg Tirzepatide 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.	Drug: Tirzepatide Administered SC Other Names: LY3298176
Experimental: 10 mg Tirzepatide 10 mg tirzepatide administered SC once a week.	Drug: Tirzepatide Administered SC Other Names: LY3298176
Experimental: 15 mg Tirzepatide 15 mg tirzepatide administered SC once a week.	Drug: Tirzepatide Administered SC Other Names: LY3298176
Placebo Comparator: Placebo Placebo administered SC once a week.	Drug: Placebo Administered SC

Outcome Measures


Primary Outcome Measures:
1.	Percentage of Participants with Absence of NASH with no Worsening of Fibrosis on Liver Histology [ Time Frame: Week 52 ] Percentage of Participants with Absence of NASH with no Worsening of Fibrosis on Liver Histology
Secondary Outcome Measures:
1.	Percentage of Participants with ≥1 Point Decrease in Fibrosis Stage with No Worsening of NASH on Liver Histology [ Time Frame: Week 52 ] Percentage of Participants with ≥1 Point Decrease in Fibrosis Stage with No Worsening of NASH on Liver Histology
2.	Percentage of Participants with ≥1 Point Increase in Fibrosis Stage on Liver Histology [ Time Frame: Week 52 ] Percentage of Participants with ≥1 Point Increase in Fibrosis Stage on Liver Histology
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 [ Time Frame: Week 52 ] Percentage of Participants that Achieve a ≥2 Point Decrease in NAS on Liver Histology, with ≥1 Point Reduction in at Least 2 NAS Components
4.	Mean Absolute Change from Baseline in Liver Fat Content by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) [ Time Frame: Baseline, Week 52 ] Mean Absolute Change from Baseline in Liver Fat Content by MRI-PDFF
5.	Mean Change from Baseline in Body Weight [ Time Frame: Baseline, Week 52 ] Mean Change from Baseline in Body Weight

Eligibility


Minimum Age:	18 Years
Maximum Age:	80 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	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)

Contacts/Locations


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) Study Director Eli Lilly and Company
Locations:	United States, Alabama
	University of Alabama-The Kirklin Clinic Birmingham, Alabama, United States, 35205
	United States, Arizona
	Synexus- Chandler Chandler, Arizona, United States, 85224
	United States, California
	Fresno Clinical Research Center Fresno, California, United States, 93720
	Velocity Clinical Research, Huntington Park Huntington Park, California, United States, 90255
	NAFLD Research Center, UCSD Altman Clinical and Translational Research Institute (ACTRI) La Jolla, California, United States, 92037
	Catalina Research Institute, LLC Montclair, California, United States, 91763
	Diabetes Medical Center of California Northridge, California, United States, 91325
	Velocity Clinical Research, Huntington Park Panorama City, California, United States, 91402
	Alliance Clinical Research, LLC Poway, California, United States, 90264
	Inland Empire Liver Foundation Rialto, California, United States, 92377
	Velocity Clinical Research, Huntington Park Santa Ana, California, United States, 92704
	United States, Florida
	Excel Medical Clinical Trials Boca Raton, Florida, United States, 33434
	Clinical Research of South Florida Coral Gables, Florida, United States, 33134
	Research Centers of America ( Hollywood ) Hollywood, Florida, United States, 33024
	East Coast Institute for Research, LLC Jacksonville, Florida, United States, 32204
	I.H.S. Health, LLC Kissimmee, Florida, United States, 34741
	Meridien Research Maitland, Florida, United States, 32751
	Clinical Pharmacology of Miami Miami, Florida, United States, 33014
	Panax Clinical Research Miami Lakes, Florida, United States, 33014
	Endoscopic Research Inc Orlando, Florida, United States, 32803
	Synexus Clinical Research US, Inc - Orlando Orlando, Florida, United States, 32806
	Synexus Clinical Research US, Inc. The Villages, Florida, United States, 32162
	United States, Georgia
	AES/Synexus - Atlanta Atlanta, Georgia, United States, 30328
	United States, Illinois
	Synexus Clinical Research US, Inc. Chicago, Illinois, United States, 60602
	United States, Indiana
	Indiana University Health Hospital Indianapolis, Indiana, United States, 46202
	United States, Iowa
	Iowa Diabetes and Endocrinology Research Center West Des Moines, Iowa, United States, 50265
	United States, Kansas
	Heartland Research Associates Newton, Kansas, United States, 67114
	Cotton O'Neil Diabetes and Endocrinology Center Topeka, Kansas, United States, 66606
	Heartland Research Associates Wichita, Kansas, United States, 67207
	United States, Louisiana
	Tandem Clinical Research GI,LLC Marrero, Louisiana, United States, 70072
	United States, Mississippi
	The National Diabetes & Obesity Research Institute (NDORI) Biloxi, Mississippi, United States, 39532
	Southern Therapy and Advanced Research (STAR) LLC Jackson, Mississippi, United States, 39216
	United States, New York
	Montefiore Medical Center Bronx, New York, United States, 10467-2490
	University at Buffalo-Clinical and Translational Research Center Buffalo, New York, United States, 14203-1070
	NYU Langone Health New York, New York, United States, 10016
	Mount Sinai School of Medicine New York, New York, United States, 10029-6574
	United States, North Carolina
	Diabetes & Endocrinology Consultants, PC Morehead City, North Carolina, United States, 28557
	United States, Pennsylvania
	Geisinger Clinic Danville, Pennsylvania, United States, 17822
	United States, Tennessee
	WR-Clinsearch, LLC Chattanooga, Tennessee, United States, 37421
	United States, Texas
	Texas Diabetes & Endocrinology, P.A. Austin, Texas, United States, 78749
	Velocity Clinical Research, Dallas Dallas, Texas, United States, 75230
	Liver Center of Texas, PLLC Dallas, Texas, United States, 75234-7858
	Synexus - Dallas Dallas, Texas, United States, 75234
	Soma Clinical Trials, LLC Denison, Texas, United States, 75020
	American Research Corporation at Texas Liver Institute San Antonio, Texas, United States, 78215
	Endeavor Clinical Trials San Antonio, Texas, United States, 78229
	Synexus - San Antonio San Antonio, Texas, United States, 78229
	United States, Virginia
	National Clinical Research, Inc Richmond, Virginia, United States, 23294
	Virginia Commonwealth University Medical Center Gastroenterology Hepatology Richmond, Virginia, United States, 23298
	United States, Washington
	Harborview Medical Center/University of Washington Seattle, Washington, United States, 98104
	Belgium
	UZ Brussel Brussel, Belgium, 1090
	Universitair Ziekenhuis Antwerpen Edegem, Belgium, 2650
	Belgium, East Flanders
	UZ Gent Hospital Gent, East Flanders, Belgium, 9000
	Belgium, Flemish Brabant
	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg Leuven, Flemish Brabant, Belgium, 3000
	Belgium, West Flanders
	AZ Delta Roeselare, West Flanders, Belgium, 8800
	France
	CHRU de Limoges Hopital Dupuytren Limoges CEDEX, France, 87042
	Hôpital Pitié-Salpêtrière - IM2A Paris, France, 75013
	Chu Haut-Leveque Pessac, France, 33604
	Centre Hospitalier Lyon Sud Pierre Benite Cedex, France, 69495
	Groupe hospitalier mutualiste Les Portes du sud Venissieux, France, 69200
	France, Cedex
	CHU Rangueil Toulouse, Cedex, France, 31059
	France, Cedex 12
	Hôpital Saint Antoine Paris, Cedex 12, France, 75012
	France, Cedex 9
	Centre Hospitalier Universitaire d'Angers Angers, Cedex 9, France, 49933
	Israel
	Rambam Medical Center Haifa, Israel, 3109601
	Shaare Zedek Medical Center Jerusalem, Israel, 91031
	Hadassah Medical Center Jerusalem, Israel, 91120
	Galilee Medical Center - Internal A Nahariya, Israel, 22100
	Israel, HaMerkaz
	Sheba Medical Center Ramat Gan, HaMerkaz, Israel, 5262100
	Israel, Ḥeifā
	Carmel Hospital Haifa, Ḥeifā, Israel, 3436212
	Italy
	Azienda Ospedaliero Universitaria Ospedali Riuniti Di Foggia Foggia, Italy, 71100
	Ospedale Santa Maria Goretti Latina, Italy, 04100
	Ospedale Maggiore di Milano Milano, Italy, 20122
	A.O. Universitaria Policlinico P. Giaccone Palermo, Italy, 90127
	A.O.U. Citta' della Salute e della Scienza di Torino Torino, Italy, 10126
	Italy, Lazio
	Policlinico Gemelli - Università Cattolica del Sacro Cuore Roma, Lazio, Italy, 00168
	Japan
	Fukuiken Saiseikai Hospital Fukui, Japan, 918-8503
	Gifu Municipal Hospital Gifu, Japan, 500-8323
	Kumamoto Shinto General Hospital Kumamoto, Japan, 862-8655
	Kyoto Furitsu Medical University Hospital Kyoto, Japan, 602-8566
	Niigata University Medical & Dental Hospital Niigata, Japan, 951-8520
	Osaka Metropolitan Univ Hosp Osaka, Japan, 545-8586
	Saga Medical School Hospital Saga, Japan, 849-8501
	Yamagata University Hospital Yamagata, Japan, 990-9585
	Japan, Aichi-ken
	Aichi Medical University Hospital Nagakute-shi, Aichi-ken, Japan, 480-1195
	Japan, Hokkaido
	JCHO Hokkaido Hospital Sapporo-shi, Hokkaido, Japan, 062-8618
	Japan, Kanagawa
	Yokohama City University Hospital Yokohama, Kanagawa, Japan, 236-0004
	National Hospital Organization Yokohama Medical Center Yokohama, Kanagawa, Japan, 2458575
	Japan, Nara-Ken
	JADECOM Nara City Hospital Nara-Shi, Nara-Ken, Japan, 630-8305
	Japan, Osaka
	Hirakata kohsai Hospital Higashi-cho, Hirakata-city, Osaka, Japan, 573-0153
	Osaka Saiseikai Suita hospital Suita, Osaka, Japan, 564-0013
	Japan, Shimane
	Shimane University Hospital Izumo, Shimane, Japan, 693-0021
	Japan, Tokyo
	Tokyo Medical and Dental University Hospital Bunkyō, Tokyo, Japan, 113-8519
	Mexico, Distrito Federal
	Grupo Medico Camino Sc México City, Distrito Federal, Mexico, 03310
	Mexico, Estado De Mexico
	Phylasis Clinicas Research Cuautitlan Izcalli, Estado De Mexico, Mexico, 54769
	Mexico, MX
	Centro de Inv y Gastroenterolo Mexico City, MX, Mexico, 06700
	Mexico, Nuevo León
	Christus Muguerza Hospital Sur Monterrey, Nuevo León, Mexico, 64000
	Poland
	Synexus Polska Oddział w Lodzi Lodz, Poland, 90-127
	Poland, Mazowieckie
	Centrum Medyczne SYNEXUS Warszawa Warszawa, Mazowieckie, Poland, 02-672
	Spain
	Instituto de Ciencias Médicas Alicante, Spain, 03004
	Hospital Universitario Ramón y Cajal Madrid, Spain, 28034
	Hospital Universitario Virgen Del Rocio Sevilla, Spain, 41013
	Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE) Seville, Spain, 41003
	Spain, Cantabria
	Hospital Universitario Marqués de Valdecilla Santander, Cantabria, Spain, 39008
	Spain, Madrid
	Hospital Puerta De Hierro Majadahonda, Madrid, Spain, 28222
	Spain, Palma De Mallorca (Baleares)
	Hospital Universitario Son Espases Palma De Mallorca, Palma De Mallorca (Baleares), Spain, 07014
	United Kingdom
	Synexus Lancashire Clinical Research Centre Chorley, United Kingdom, PR7 7NA
	Synexus North East Clinical Research Centre Hexham, United Kingdom, NE46 1QJ
	Aintree University Hospital NHS Foundation Trust Liverpool, United Kingdom, L9 7AL
	Barts Health NHS Trust London, United Kingdom, E1 1FR
	St. George's Hospital London, United Kingdom, SW17 0QT
	Imperial College London and Imperial College Healthcare NHS Trust London, United Kingdom, W2 1NY
	Synexus Manchester Clinical Research Centre Manchester, United Kingdom, M15 6SX
	Synexus North Teesside Clinical Research Centre Stockton-on-Tees, United Kingdom, TS19 8PE
	United Kingdom, Birmingham
	Synexus Midlands Clinical Research Center Edgbaston, Birmingham, United Kingdom, B15 2SQ
	United Kingdom, Greater London
	Kings College Hospital London, Greater London, United Kingdom, SE5 9RS
	United Kingdom, Nottinghamshire
	Queen's Medical Centre, Nottingham University Hospitals Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
	United Kingdom, Oxford
	John Radcliffe Hospital Headington, Oxford, United Kingdom, OX3 9DU
	United Kingdom, West Midlands
	Queen Elizabeth Hospital Birmingham, West Midlands, United Kingdom, B15 2TH

IPDSharing


Plan to Share IPD:	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.
	Supporting Information: Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (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.
	URL: http://vivli.org/

References


Citations:
Links:	URL: https://trials.lillytrialguide.com/en-US/trial/3lQTuBFU3GBu9vi4SAlDDp Description: A Study of Tirzepatide (LY3298176) in Participants With Nonalcoholic Steatohepatitis (NASH)
Available IPD/Information: