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).
Brief Title
A Study of Tirzepatide (LY3298176) in Participants With Nonalcoholic Steatohepatitis (NASH)
Completion Date
Completion Date Type
Actual
Conditions
Nonalcoholic Steatohepatitis
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)
* 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)
Inclusion 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)
* 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)
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
80 Years
Minimum Age
18 Years
NCT Id
NCT04166773
Org Class
Industry
Org Full Name
Eli Lilly and Company
Org Study Id
17361
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome 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.
Outcome Measure
Percentage of Participants With Absence of Nonalcoholic Steatohepatitis (NASH) With no Worsening of Fibrosis on Liver Histology
Outcome Time Frame
Week 52
Secondary Ids
Secondary Id
I8F-MC-GPHR
Secondary Id
2019-001550-26
Secondary Outcomes
Outcome 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).
Outcome Time Frame
Week 52
Outcome Measure
Percentage of Participants With ≥1 Point Decrease in Fibrosis Stage With No Worsening of NASH on Liver Histology
Outcome Description
Participants were evaluated with the NASH CRN scoring system with ≥1 stage increase in fibrosis.
Outcome Time Frame
Week 52
Outcome Measure
Percentage of Participants With ≥1 Point Increase in Fibrosis Stage on Liver Histology
Outcome 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.
Outcome Time Frame
Week 52
Outcome Measure
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
Outcome 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.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Mean Absolute Change From Baseline in Liver Fat Content by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)
Outcome 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.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Mean Change From Baseline in Body Weight
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
80
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Samuel Sigal
Investigator Email
ssigal@montefiore.org
Investigator Phone
718-920-6240