The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT07165028




Registration number
NCT07165028
Ethics application status
Date submitted
28/08/2025
Date registered
10/09/2025
Date last updated
10/09/2025

Titles & IDs
Public title
A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes)
Scientific title
A Master Protocol for a Randomized, Controlled, Clinical Trial of Multiple Pharmacologic Agents in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease Who Are at Increased Risk of Developing Major Adverse Liver Outcomes
Secondary ID [1] 0 0
2025-522674-36-00
Secondary ID [2] 0 0
27610
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metabolic Dysfunction-Associated Steatotic Liver Disease 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tirzepatide
Treatment: Drugs - Retatrutide
Treatment: Drugs - Placebo

Experimental: Tirzepatide (TZ01) - Participants will receive tirzepatide subcutaneously (SC)

Placebo comparator: Placebo (TZ01) - Participants will receive placebo SC

Experimental: Retatrutide (RT01) - Participants will receive retatrutide SC

Placebo comparator: Placebo (RT01) - Participants will receive placebo SC


Treatment: Drugs: Tirzepatide
Administered SC

Treatment: Drugs: Retatrutide
Administered SC

Treatment: Drugs: Placebo
Administered SC

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to First Occurrence of Any Component of the Composite Endpoint for Major Adverse Liver Outcomes (MALO)
Timepoint [1] 0 0
Baseline up to Study Completion (about 224 weeks)
Secondary outcome [1] 0 0
Change from Baseline in Enhanced Liver Fibrosis (ELF) Score
Timepoint [1] 0 0
Baseline, Week 104
Secondary outcome [2] 0 0
Change from Baseline in Vibration-Controlled Transient Elastography Liver Stiffness Measurement (VCTE LSM)
Timepoint [2] 0 0
Baseline, Week 104
Secondary outcome [3] 0 0
Percent Change from Baseline in Liver Fat Content (LFC)
Timepoint [3] 0 0
Baseline, Week 104
Secondary outcome [4] 0 0
Time to Occurrence of Progression to Cirrhosis
Timepoint [4] 0 0
Baseline up to Study Completion (about 224 weeks)
Secondary outcome [5] 0 0
Change from Baseline in Aspartate Aminotransferase (AST)
Timepoint [5] 0 0
Baseline, Study Completion (about 224 weeks)
Secondary outcome [6] 0 0
Change from Baseline in Alanine Aminotransferase (ALT)
Timepoint [6] 0 0
Baseline, Study Completion (about 224 weeks)
Secondary outcome [7] 0 0
Change from Baseline in Body Weight
Timepoint [7] 0 0
Baseline, Study Completion (about 224 weeks)
Secondary outcome [8] 0 0
Change from Baseline in Non-Alcoholic Steatohepatitis-CHECK Score (NASH-CHECK)
Timepoint [8] 0 0
Baseline, Week 104
Secondary outcome [9] 0 0
Time to First Occurrence of Any Component Event of the Composite Endpoint of Major Adverse Cardiovascular Events (MACE-3)
Timepoint [9] 0 0
Baseline up to Study Completion (about 224 weeks)

Eligibility
Key inclusion criteria
* Have liver fat content =8%
* Have ELF score of =9 and =10.8 at screening
* Have VCTE LSM =10 kilopascal (kPa) and <20 kPa at screening
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Have any other type of liver disease other than MASLD
* Have a body mass index (BMI) <25 kilogram per square meter (kg/m2)
* Prior decompensated liver disease (history of esophageal/gastric varices, ascites, hepatic encephalopathy)
* Have lost more than 11 pounds within the 3 months prior to screening
* Have a hemoglobin A1c (HbA1c) greater than 10%
* Have type 1 diabetes

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Nightingale Research - Adelaide
Recruitment hospital [2] 0 0
Core Research Group - Brisbane
Recruitment hospital [3] 0 0
Ipswich Hospital - Ipswich
Recruitment hospital [4] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [5] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
4064 - Brisbane
Recruitment postcode(s) [3] 0 0
4305 - Ipswich
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Nevada
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Rhode Island
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
Argentina
State/province [22] 0 0
Buenos Aires
Country [23] 0 0
Argentina
State/province [23] 0 0
Córdoba
Country [24] 0 0
Argentina
State/province [24] 0 0
Mar del Plata
Country [25] 0 0
Argentina
State/province [25] 0 0
Ramos Mejía
Country [26] 0 0
Argentina
State/province [26] 0 0
Rosario
Country [27] 0 0
Argentina
State/province [27] 0 0
Santa Fe
Country [28] 0 0
Austria
State/province [28] 0 0
Graz
Country [29] 0 0
Austria
State/province [29] 0 0
Salzburg
Country [30] 0 0
Austria
State/province [30] 0 0
Vienna
Country [31] 0 0
Austria
State/province [31] 0 0
Wiener Neustadt
Country [32] 0 0
Belgium
State/province [32] 0 0
Brussels
Country [33] 0 0
Belgium
State/province [33] 0 0
Edegem
Country [34] 0 0
Belgium
State/province [34] 0 0
Ghent
Country [35] 0 0
Belgium
State/province [35] 0 0
Kortrijk
Country [36] 0 0
Belgium
State/province [36] 0 0
Ostend
Country [37] 0 0
Belgium
State/province [37] 0 0
Roeselare
Country [38] 0 0
Belgium
State/province [38] 0 0
Sint-Niklaas
Country [39] 0 0
Brazil
State/province [39] 0 0
Aracaju
Country [40] 0 0
Brazil
State/province [40] 0 0
Belo Horizonte
Country [41] 0 0
Brazil
State/province [41] 0 0
Botucatu
Country [42] 0 0
Brazil
State/province [42] 0 0
Curitiba
Country [43] 0 0
Brazil
State/province [43] 0 0
Goiânia
Country [44] 0 0
Brazil
State/province [44] 0 0
Lago Sul
Country [45] 0 0
Brazil
State/province [45] 0 0
Porto Alegre
Country [46] 0 0
Brazil
State/province [46] 0 0
Recife
Country [47] 0 0
Brazil
State/province [47] 0 0
Rio de Janeiro
Country [48] 0 0
Brazil
State/province [48] 0 0
São Bernardo do Campo
Country [49] 0 0
Brazil
State/province [49] 0 0
São Paulo
Country [50] 0 0
Brazil
State/province [50] 0 0
Vitória
Country [51] 0 0
Canada
State/province [51] 0 0
Calgary
Country [52] 0 0
Canada
State/province [52] 0 0
Chicoutimi
Country [53] 0 0
Canada
State/province [53] 0 0
London
Country [54] 0 0
Canada
State/province [54] 0 0
Québec
Country [55] 0 0
Canada
State/province [55] 0 0
Vancouver
Country [56] 0 0
China
State/province [56] 0 0
Beijing
Country [57] 0 0
China
State/province [57] 0 0
Changchun
Country [58] 0 0
China
State/province [58] 0 0
Changsha
Country [59] 0 0
China
State/province [59] 0 0
Foshan
Country [60] 0 0
China
State/province [60] 0 0
Guangzhou
Country [61] 0 0
China
State/province [61] 0 0
Guiyang
Country [62] 0 0
China
State/province [62] 0 0
Hangzhou
Country [63] 0 0
China
State/province [63] 0 0
Pingxiang
Country [64] 0 0
China
State/province [64] 0 0
Shanghai
Country [65] 0 0
China
State/province [65] 0 0
Shijiazhuang
Country [66] 0 0
China
State/province [66] 0 0
Wenzhou
Country [67] 0 0
China
State/province [67] 0 0
Xi'an
Country [68] 0 0
China
State/province [68] 0 0
Zhoukou
Country [69] 0 0
Czechia
State/province [69] 0 0
Liberec
Country [70] 0 0
France
State/province [70] 0 0
Amiens
Country [71] 0 0
France
State/province [71] 0 0
Angers
Country [72] 0 0
France
State/province [72] 0 0
Besançon
Country [73] 0 0
France
State/province [73] 0 0
Clichy
Country [74] 0 0
France
State/province [74] 0 0
Dijon
Country [75] 0 0
France
State/province [75] 0 0
La Roche-sur-Yon
Country [76] 0 0
France
State/province [76] 0 0
Lille
Country [77] 0 0
France
State/province [77] 0 0
Limoges
Country [78] 0 0
France
State/province [78] 0 0
Nice
Country [79] 0 0
France
State/province [79] 0 0
Paris
Country [80] 0 0
France
State/province [80] 0 0
Pessac
Country [81] 0 0
France
State/province [81] 0 0
Pierre-Bénite
Country [82] 0 0
France
State/province [82] 0 0
Rennes
Country [83] 0 0
France
State/province [83] 0 0
Toulouse
Country [84] 0 0
France
State/province [84] 0 0
Vénissieux
Country [85] 0 0
Germany
State/province [85] 0 0
Berlin
Country [86] 0 0
Germany
State/province [86] 0 0
Dresden
Country [87] 0 0
Germany
State/province [87] 0 0
Düsseldorf
Country [88] 0 0
Germany
State/province [88] 0 0
Freiburg im Breisgau
Country [89] 0 0
Germany
State/province [89] 0 0
Heidelberg
Country [90] 0 0
Germany
State/province [90] 0 0
Homburg
Country [91] 0 0
Germany
State/province [91] 0 0
Leipzig
Country [92] 0 0
Germany
State/province [92] 0 0
Mainz
Country [93] 0 0
Hungary
State/province [93] 0 0
Budapest
Country [94] 0 0
Hungary
State/province [94] 0 0
Debrecen
Country [95] 0 0
Hungary
State/province [95] 0 0
Nyíregyháza
Country [96] 0 0
India
State/province [96] 0 0
Ahmedabad
Country [97] 0 0
India
State/province [97] 0 0
Jaipur
Country [98] 0 0
India
State/province [98] 0 0
Ludhiana
Country [99] 0 0
India
State/province [99] 0 0
Mohali
Country [100] 0 0
India
State/province [100] 0 0
Nagpur
Country [101] 0 0
India
State/province [101] 0 0
New Delhi
Country [102] 0 0
India
State/province [102] 0 0
Surat
Country [103] 0 0
India
State/province [103] 0 0
Wardha
Country [104] 0 0
Italy
State/province [104] 0 0
Florence
Country [105] 0 0
Italy
State/province [105] 0 0
Milan
Country [106] 0 0
Italy
State/province [106] 0 0
Naples
Country [107] 0 0
Italy
State/province [107] 0 0
Padua
Country [108] 0 0
Italy
State/province [108] 0 0
Palermo
Country [109] 0 0
Italy
State/province [109] 0 0
Roma
Country [110] 0 0
Italy
State/province [110] 0 0
Rome
Country [111] 0 0
Italy
State/province [111] 0 0
Rozzano
Country [112] 0 0
Italy
State/province [112] 0 0
Torino
Country [113] 0 0
Mexico
State/province [113] 0 0
Chihuahua City
Country [114] 0 0
Mexico
State/province [114] 0 0
Cuauhtémoc
Country [115] 0 0
Mexico
State/province [115] 0 0
Monterrey
Country [116] 0 0
Mexico
State/province [116] 0 0
Zapopan
Country [117] 0 0
Romania
State/province [117] 0 0
Bucharest
Country [118] 0 0
Romania
State/province [118] 0 0
Cluj-Napoca
Country [119] 0 0
Romania
State/province [119] 0 0
Constan?a
Country [120] 0 0
Romania
State/province [120] 0 0
Satu Mare
Country [121] 0 0
South Korea
State/province [121] 0 0
Guri-si
Country [122] 0 0
South Korea
State/province [122] 0 0
Incheon
Country [123] 0 0
South Korea
State/province [123] 0 0
Seoul
Country [124] 0 0
Spain
State/province [124] 0 0
A Coruña
Country [125] 0 0
Spain
State/province [125] 0 0
Badalona
Country [126] 0 0
Spain
State/province [126] 0 0
Barcelona
Country [127] 0 0
Spain
State/province [127] 0 0
Ferrol
Country [128] 0 0
Spain
State/province [128] 0 0
Huelva
Country [129] 0 0
Spain
State/province [129] 0 0
Madrid
Country [130] 0 0
Spain
State/province [130] 0 0
Palma
Country [131] 0 0
Spain
State/province [131] 0 0
Pontevedra
Country [132] 0 0
Spain
State/province [132] 0 0
Santander
Country [133] 0 0
Spain
State/province [133] 0 0
Seville
Country [134] 0 0
Spain
State/province [134] 0 0
Valencia
Country [135] 0 0
Sweden
State/province [135] 0 0
Linköping
Country [136] 0 0
Taiwan
State/province [136] 0 0
Taipei
Country [137] 0 0
Ukraine
State/province [137] 0 0
Ivano-Frankivsk
Country [138] 0 0
Ukraine
State/province [138] 0 0
Kiev
Country [139] 0 0
Ukraine
State/province [139] 0 0
Kyiv
Country [140] 0 0
Ukraine
State/province [140] 0 0
Lviv
Country [141] 0 0
Ukraine
State/province [141] 0 0
Vinnytsia
Country [142] 0 0
Ukraine
State/province [142] 0 0
Zhytomyr
Country [143] 0 0
United Kingdom
State/province [143] 0 0
Clifton
Country [144] 0 0
United Kingdom
State/province [144] 0 0
Enfield
Country [145] 0 0
United Kingdom
State/province [145] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
Address 0 0
Country 0 0
Phone 0 0
1-317-615-4559
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
Data are available 6 months after the primary publication or approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Available to whom?
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.