Clinical trial NCT04166773: A Study of Tirzepatide (LY3298176) in Participants With Nonalcoholic Steatohepatitis (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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-11-18
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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)

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