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Completed

NCT Number: NCT04166773

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

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).

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Key information

Conditions

Nonalcoholic Steatohepatitis Digestive System Diseases Fatty Liver Liver Diseases Non-alcoholic Fatty Liver Disease

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Antwerp University Hospital, Edegem, Antwerpen, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

  • 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)

Treatment and study plan

Tirzepatide

Drug

Administered SC

Other names: LY3298176

Placebo

Drug

Administered SC

Primary outcomes

  1. Percentage of Participants With Absence of Nonalcoholic Steatohepatitis (NASH) With no Worsening of Fibrosis on Liver Histology

    Time frame: 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 outcomes

  1. Percentage of Participants With ≥1 Point Decrease in Fibrosis Stage With No Worsening of NASH on Liver Histology

    Time frame: 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).

  2. Percentage of Participants With ≥1 Point Increase in Fibrosis Stage on Liver Histology

    Time frame: Week 52

    Participants were evaluated with the NASH CRN scoring system with ≥1 stage increase in fibrosis.

  3. 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

    Time frame: 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.

  4. Mean Absolute Change From Baseline in Liver Fat Content by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)

    Time frame: 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.

  5. Mean Change From Baseline in Body Weight

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study 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)

Acronym: SYNERGY-NASH

Important dates

Study start
2019
Primary completion
2023
Study completion
2024
First posted
Nov 18, 2019
Registry last updated
Jan 24, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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