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

• ClinicalTrials.gov Identifier: NCT04166773
• Recruitment Status: Completed
• First Posted: November 18, 2019
• Last Update Posted: April 18, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: November 15, 2019
• First Posted Date: November 18, 2019
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: November 19, 2019
• Actual Primary Completion Date: December 11, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 15, 2019)

Percentage of Participants with Absence of NASH with no Worsening of Fibrosis on Liver Histology [ Time Frame: Week 52 ]

Percentage of Participants with Absence of NASH with no Worsening of Fibrosis on Liver Histology

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 15, 2019)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Nonalcoholic Steatohepatitis

Intervention

• Drug: Tirzepatide
  Administered SC
  Other Name: LY3298176
• Drug: Placebo
  Administered SC

Study Arms

• Experimental: 5 mg Tirzepatide
  5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
  Intervention: Drug: Tirzepatide
• Experimental: 10 mg Tirzepatide
  10 mg tirzepatide administered SC once a week.
  Intervention: Drug: Tirzepatide
• Experimental: 15 mg Tirzepatide
  15 mg tirzepatide administered SC once a week.
  Intervention: Drug: Tirzepatide
• Placebo Comparator: Placebo
  Placebo administered SC once a week.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 15, 2019): 196
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 10, 2024
• Actual Primary Completion Date: December 11, 2023 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Israel, Italy, Japan, Mexico, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04166773
• Other Study ID Numbers: 17361; I8F-MC-GPHR ( Other Identifier: Eli Lilly and Company ); 2019-001550-26 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: http://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: 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); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: April 2024