Tirzepatide versus placebo in NASH

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 196

Inclusion Criteria

- Female or male 18 to 80 years of age (inclusive)
- Body Mass Index (BMI) = 27kg/m² and =50 kg/m2
- Participants with T2DM (HbA1c = 9.5% at screening, treated with diet and/or exercice, or treated with oral antihyperglycemic medication (as detailed in the protocol))
- Participants without diagnosed T2DM (HbA1c < 6.5% at screening and fasting glucose < 7.0 mmol/L)
- Diagnosis of NASH by liver biopsy
- NAFLD Activity Score (NAS) = 4 with = 1 point for each component
- Fibrosis stage 2 or 3 according to the NASH CRN scoring system
- Stable body weight for at least 3 months. For participants entering the study with a liver biopsy done between 3 to 6 months from the screening visit, body weight must be stable (<5% body weight change) for the period of time between the biopsy and the screening visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 156
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

- Alcohol consumption > 14 units/week for women and > 21 units/week for men
- Fibrosis stages 0 and 1 according to the NASH CRN scoring system
- Cirrhosis (fibrosis stage 4)
- Platelet count < 150,000/mm3
- Evidence of other forms of chronic liver disease
- Uncontrolled T2DM

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate that Tirzepatide 5mg, 10mg or 15mg administered SC QW is superior to placebo for NASH resolution with no worsening of fibrosis at Week 52.;Secondary Objective: To demonstrate that Tirzepatide 5mg, 10mg or 15mg administered SC QW is superior to placebo at Week 52 for :<br>- Regression of fibrosis with no worsening of NASH<br>- Prevention of fibrosis progression<br>- Decreasing NAS by = 2 points<br>- Decreasing liver fat content<br>- Decreasing body weight;Primary end point(s): Proportion of participants classified with absence of NASH with no worsening of fibrosis on liver histology;Timepoint(s) of evaluation of this end point: 52 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): From baseline :<br>- Proportion of participants with =1 point decrease in fibrosis stage with no worsening of NASH on liver histology<br>- Proportion of participants with =1 point increase in fibrosis stage on liver histology<br>- Proportion of participants that achieve a =2 point decrease in NAS on liver histology, with =1 point reduction in at least 2 NAS components (steatosis, hepatocellular ballooning, lobular inflammation)<br>- Mean absolute change in liver fat content by MRI-PDFF<br>- Mean change in body weight;Timepoint(s) of evaluation of this end point: 52 weeks