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

Study Overview
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Brief Summary
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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).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Comparing the Efficacy and Safety of Tirzepatide Versus Placebo in Patients With Nonalcoholic Steatohepatitis (NASH)

Conditions
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Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Tirzepatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 mg Tirzepatide<br>5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: 10 mg Tirzepatide<br>10 mg tirzepatide administered SC once a week. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: 15 mg Tirzepatide<br>15 mg tirzepatide administered SC once a week. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Placebo Comparator: Placebo<br>Placebo administered SC once a week. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Absence of NASH with no Worsening of Fibrosis on Liver Histology | Percentage of Participants with Absence of NASH with no Worsening of Fibrosis on Liver Histology | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with ≥1 Point Decrease in Fibrosis Stage with No Worsening of NASH on Liver Histology | Percentage of Participants with ≥1 Point Decrease in Fibrosis Stage with No Worsening of NASH on Liver Histology | Week 52 | 
| Percentage of Participants with ≥1 Point Increase in Fibrosis Stage on Liver Histology | Percentage of Participants with ≥1 Point Increase in Fibrosis Stage on Liver Histology | Week 52 | 
| 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 | Percentage of Participants that Achieve a ≥2 Point Decrease in NAS on Liver Histology, with ≥1 Point Reduction in at Least 2 NAS Components | Week 52 | 
| Mean Absolute Change from Baseline in Liver Fat Content by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | Mean Absolute Change from Baseline in Liver Fat Content by MRI-PDFF | Baseline, Week 52 | 
| Mean Change from Baseline in Body Weight | Mean Change from Baseline in Body Weight | Baseline, Week 52 |