Skip to content

Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

Short name SYNERGY-NASH

NCTNCT04166773 (opens ClinicalTrials.gov in a new tab)Other id17361Other idI8F-MC-GPHROther id2019-001550-26Other id2019
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 2
Enrollment
190 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Double masking
Countries
10 countries

United States, Belgium, France, Israel, Italy, Japan, Mexico, Poland, Spain, United Kingdom

Start
19 Nov 2019
Primary completion
11 Dec 2023
Completion
10 Jan 2024
First posted
18 Nov 2019
Last update posted
24 Jan 2025
Conditions
Nonalcoholic Steatohepatitis

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2019202020212022202320242025
  1. Ph 2

    SYNERGY-NASH

    NCT04166773

    19 Nov 2019 to 10 Jan 2024

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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).

Interventions

  • TirzepatideDrug
  • PlaceboDrug

Arms4

  • Experimental

    5 mg Tirzepatide

    5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

  • Experimental

    10 mg Tirzepatide

    10 mg tirzepatide administered SC once a week.

  • Experimental

    15 mg Tirzepatide

    15 mg tirzepatide administered SC once a week.

  • Placebo comparator

    Placebo

    Placebo administered SC once a week.

Primary outcomes1

Outcomes the sponsor listed as primary.

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

    Time frame · Week 52

    Registry description

    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(5)

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

    Time frame · Week 52

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· Week 52

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

GroupValue (Percentage of participants)
5 mg Tirzepatide51.84
10 mg Tirzepatide63.13
15 mg Tirzepatide73.92
Placebo12.62
Secondary and other outcome results(5)
Secondary outcomeNumber· Week 52

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

GroupValue (Percentage of participants)
5 mg Tirzepatide59.21
10 mg Tirzepatide53.35
15 mg Tirzepatide54.3
Placebo32.51
Secondary outcomeNumber· Week 52

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

GroupValue (Percentage of participants)
5 mg Tirzepatide12.04
10 mg Tirzepatide9.81
15 mg Tirzepatide5.53
Placebo13.03
Secondary outcomeNumber· 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

GroupValue (Percentage of participants)
5 mg Tirzepatide81.02
10 mg Tirzepatide86.55
15 mg Tirzepatide88.77
Placebo38.09
Secondary outcomeLeast squares mean· Baseline to Week 52

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

GroupValue (absolute percentage of liver fat)Spread
5 mg Tirzepatide-10.121.165
10 mg Tirzepatide-10.151.071
15 mg Tirzepatide-11.341.107
Placebo-1.311.142
Secondary outcomeLeast squares mean· Baseline to Week 52

Mean Change From Baseline in Body Weight

GroupValue (Kilogram (kg))Spread
5 mg Tirzepatide-11.461.404
10 mg Tirzepatide-14.221.380
15 mg Tirzepatide-17.881.376
Placebo-1.041.392

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
5 mg TirzepatideParticipants received 5 mg tirzepatide administered SC QW for 52 weeks \[initially 2.5 mg tirzepatide SC QW for 4 weeks, then 5 mg tirzepatide SC QW from weeks 5-52\].0 / 475 / 4743 / 47
10 mg TirzepatideParticipants received 10 mg tirzepatide administered SC QW for 52 weeks \[initially 2.5 mg tirzepatide SC QW for 4 weeks, then dose escalated to 5 mg, 7.5 mg, and 10 mg every 4 weeks until target dose (10 mg) was reached\].0 / 474 / 4743 / 47
15 mg TirzepatideParticipants received 15 mg tirzepatide administered SC QW for 52 weeks \[initially 2.5 mg tirzepatide SC QW for 4 weeks, then dose escalated to 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg every 4 weeks until target dose (15 mg) was reached\].0 / 480 / 4844 / 48
PlaceboParticipants received placebo administered SC QW for 52 weeks.0 / 483 / 4840 / 48

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

More studies

1 study on this page

Indexing hint: Randomized controlled trial · 2024

Corrected

Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.

Loomba et al. 2024The New England journal of medicinecited by 730

PMID 38856224DOI 10.1056/nejmoa2401943PUB-38856224

Full text at the publisher
Publisher pageRead the notice

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 80 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
* 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)

PepBank is a research reference. Talk to a doctor before you use any peptide.