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

Phase 2
Completed
Conditions
Nonalcoholic Steatohepatitis
Interventions
Drug: Placebo
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
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo administered SC once a week.
5 mg TirzepatideTirzepatide5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
10 mg TirzepatideTirzepatide10 mg tirzepatide administered SC once a week.
15 mg TirzepatideTirzepatide15 mg tirzepatide administered SC once a week.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Absence of Nonalcoholic Steatohepatitis (NASH) With no Worsening of Fibrosis on Liver HistologyWeek 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
NameTimeMethod
Percentage of Participants With ≥1 Point Decrease in Fibrosis Stage With No Worsening of NASH on Liver HistologyWeek 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 HistologyWeek 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 ComponentsWeek 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 WeightBaseline 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)

University of Alabama-The Kirklin Clinic

🇺🇸

Birmingham, Alabama, United States

Synexus Clinical Research US, Inc.

🇺🇸

San Antonio, Texas, 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

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University of Alabama-The Kirklin Clinic
🇺🇸Birmingham, Alabama, United States

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