A Study of Tirzepatide (LY3298176) in Participants With Nonalcoholic Steatohepatitis (NASH)
- Registration Number
- NCT04166773
- Lead Sponsor
- Eli Lilly and Company
- 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
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 190
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo administered SC once a week. 5 mg Tirzepatide Tirzepatide 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. 10 mg Tirzepatide Tirzepatide 10 mg tirzepatide administered SC once a week. 15 mg Tirzepatide Tirzepatide 15 mg tirzepatide administered SC once a week.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Absence of Nonalcoholic Steatohepatitis (NASH) With no Worsening of Fibrosis on Liver Histology Week 52 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With ≥1 Point Decrease in Fibrosis Stage With No Worsening of NASH on Liver Histology Week 52 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).
Percentage of Participants With ≥1 Point Increase in Fibrosis Stage on Liver Histology Week 52 Participants were evaluated with the NASH CRN scoring system with ≥1 stage increase in fibrosis.
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 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.
Mean Absolute Change From Baseline in Liver Fat Content by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) Baseline to Week 52 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.
Mean Change From Baseline in Body Weight Baseline to Week 52 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.
Trial Locations
- Locations (108)
Texas Diabetes & Endocrinology, P.A.
🇺🇸Round Rock, Texas, United States
Kumamoto Shinto General Hospital
🇯🇵Kumamoto, Japan
Diabetes & Endocrinology Consultants, PC
🇺🇸Morehead City, North Carolina, United States
Antwerp University Hospital
🇧🇪Edegem, Antwerpen, Belgium
UZ Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Dallas Diabetes Research Center
🇺🇸Dallas, Texas, United States
Groupe Hospitalier Mutualiste Les Portes du Sud
🇫🇷Vénissieux, Rhône-Alpes, France
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
National Clinical Research, Inc
🇺🇸Richmond, Virginia, United States
UZ Leuven
🇧🇪Leuven, Vlaams-Brabant, Belgium
CHU Bordeaux Haut-Leveque
🇫🇷Pessac, Aquitaine, France
Galilee Medical Center
🇮🇱Nahariya, HaTsafon, Israel
Synexus Clinical Research
🇺🇸Chicago, Illinois, United States
WR-Clinsearch, LLC
🇺🇸Chattanooga, Tennessee, United States
Radiant Research - Dallas North
🇺🇸Dallas, Texas, United States
Tandem Clinical Research
🇺🇸Marrero, Louisiana, United States
UZ Brussel
🇧🇪Brussels, Bruxelles-Capitale, Région De, Belgium
Buffalo Clinical and Translational Research Center
🇺🇸Buffalo, New York, United States
The National Diabetes & Obesity Research Institute
🇺🇸Biloxi, Mississippi, United States
NYU Langone Health
🇺🇸New York, New York, United States
Hôpital Saint Antoine
🇫🇷Paris, France
Fukuiken Saiseikai Hospital
🇯🇵Fukui, Japan
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Bénite, Rhône, France
Rambam Health Care Campus
🇮🇱Haifa, HaTsafon, Israel
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Madrid, Spain
National Hospital Organization Yokohama Medical Center
🇯🇵Yokohama, Kanagawa, Japan
JADECOM Nara City Hospital
🇯🇵Nara-Shi, Nara-Ken, Japan
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hirakata kohsai Hospital
🇯🇵Higashi-cho, Hirakata-city, Osaka, Japan
Clínica Juaneda
🇪🇸Palma de Mallorca, Balears [Baleares], Spain
Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE)
🇪🇸Sevilla, Spain
Synexus Polska Oddział w Lodzi
🇵🇱Lodz, Łódzkie, Poland
Aintree University Hospital NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Synexus Manchester Clinical Research Centre
🇬🇧Manchester, United Kingdom
Instituto de Ciencias Médicas
🇪🇸Alicante, Spain
Royal London Hospital
🇬🇧London, England, United Kingdom
John Radcliffe Hospital
🇬🇧Headington, Oxford, United Kingdom
Synexus Midlands Clinical Research Centre
🇬🇧Birmingham, United Kingdom
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Harborview Medical Center/University of Washington
🇺🇸Seattle, Washington, United States
Fresno Clinical Research Center
🇺🇸Fresno, California, United States
National Research Institute - Huntington Park
🇺🇸Huntington Park, California, United States
UCSD - Altman Clinical and Translational Research Institute (ACTRI)
🇺🇸La Jolla, California, United States
National Research Institute - Wilshire
🇺🇸Los Angeles, California, United States
Catalina Research Institute, LLC
🇺🇸Montclair, California, United States
Diabetes Medical Center of California
🇺🇸Northridge, California, United States
Velocity Clinical Research, Panorama City
🇺🇸Panorama City, California, United States
Inland Empire Clinical Trials, LLC
🇺🇸Rialto, California, United States
Excel Medical Clinical Trials
🇺🇸Boca Raton, Florida, United States
Velocity Clinical Research, Santa Ana
🇺🇸Santa Ana, California, United States
Research Centers of America ( Hollywood )
🇺🇸Hollywood, Florida, United States
East Coast Institute for Research, LLC
🇺🇸Jacksonville, Florida, United States
IHS Health Research
🇺🇸Kissimmee, Florida, United States
Accel Research Sites - Maitland Clinical Research Unit
🇺🇸Maitland, Florida, United States
Clinical Pharmacology of Miami
🇺🇸Miami, Florida, United States
Shimane University Hospital
🇯🇵Izumo, Shimane, Japan
Gifu Municipal Hospital
🇯🇵Gifu, Japan
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Synexus North Teesside Clinical Research Centre
🇬🇧Stockton on Tees, Stockton-on-Tees, United Kingdom
Indiana University Health Hospital
🇺🇸Indianapolis, Indiana, United States
Cotton O'Neil Clinical Research Center
🇺🇸Topeka, Kansas, United States
Alliance for Multispecialty Research, LLC
🇺🇸Wichita, Kansas, United States
Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren
🇫🇷Limoges, Haute-Vienne, France
Centre Hospitalier Universitaire d'Angers
🇫🇷Angers, Maine-et-Loire, France
Shaare Zedek Medical Center
🇮🇱Jerusalem, Yerushalayim, Israel
Synexus Clinical Research US, Inc.
🇺🇸San Antonio, Texas, United States
American Research Corporation at Texas Liver Institute
🇺🇸San Antonio, Texas, United States
A.O.U. Policlinico Paolo Giaccone
🇮🇹Palermo, Sicilia, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti Di Foggia
🇮🇹Foggia, Italy
Ospedale Santa Maria Goretti
🇮🇹Latina, Italy
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
University of Alabama-The Kirklin Clinic
🇺🇸Birmingham, Alabama, United States
King's College Hospital
🇬🇧London, London, City Of, United Kingdom
Imperial College London - St Mary's Hospital
🇬🇧London, Westminster, United Kingdom
Pitie Salpetriere University Hospital
🇫🇷Paris, France
Iowa Diabetes and Endocrinology Research Center
🇺🇸West Des Moines, Iowa, United States
Liver Center of Texas, PLLC
🇺🇸Dallas, Texas, United States
Texoma Medical Center
🇺🇸Denison, Texas, United States
Virginia Commonwealth University (VCU) Medical Center
🇺🇸Richmond, Virginia, United States
Endeavor Clinical Trials
🇺🇸San Antonio, Texas, United States
The Center for Digestive Health
🇺🇸Orlando, Florida, United States
St. George's Hospital
🇬🇧London, England, United Kingdom
JCHO Hokkaido Hospital
🇯🇵Sapporo-shi, Hokkaido, Japan
Osaka Saiseikai Suita hospital
🇯🇵Suita, Osaka, Japan
Saga University Hospital
🇯🇵Saga, Japan
Phylasis Clinicas Research
🇲🇽Cuautitlan Izcalli, Distrito Federal, Mexico
Sheba Medical Center
🇮🇱Ramat Gan, HaMerkaz, Israel
Carmel Hospital
🇮🇱Haifa, Israel
Yokohama City University Hospital
🇯🇵Yokohama, Kanagawa, Japan
Tokyo Medical And Dental University Medical Hospital
🇯🇵Bunkyō, Tokyo, Japan
Yamagata University Hospital
🇯🇵Yamagata, Japan
Synexus Clinical Research Centre - Lancashire
🇬🇧Chorley, Lancashire, United Kingdom
Southern Therapy and Advanced Research (STAR) LLC
🇺🇸Jackson, Mississippi, United States
Christus Muguerza Hospital Sur
🇲🇽Monterrey, Nuevo León, Mexico
Hadassah Medical Center
🇮🇱Jerusalem, Yerushalayim, Israel
University Hospital,Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Centro de Investigación y Gastroenterología
🇲🇽Cuauhtémoc, Mexico
Queen's Medical Centre, Nottingham University Hospitals
🇬🇧Nottingham, Nottinghamshire, United Kingdom
Queen Elizabeth Hospital Birmingham
🇬🇧Birmingham, England, United Kingdom
AZ Delta vzw
🇧🇪Roeselare, West-Vlaanderen, Belgium
Aichi Medical University Hospital
🇯🇵Nagakute-shi, Aichi-ken, Japan
Niigata University Medical & Dental Hospital
🇯🇵Niigata, Japan
Grupo Medico Camino Sc
🇲🇽Mexico City, Distrito Federal, Mexico
Synexus Polska Sp. z o.o. Oddzial w Warszawie
🇵🇱Warsaw, Mazowieckie, Poland
Synexus North East Clinical Research Centre
🇬🇧Hexham, England, United Kingdom
Montefiore Medical Center
🇺🇸Bronx, New York, United States