Different Doses of BI 1467335 Compared to Placebo in Patients With Clinical Evidence of NASH

Inclusion criteria

• Clinical evidence of NASH defined as a. histological evidence of NASH (no more than 3 years prior to screening) OR b. clinical imaging results suggestive of NASH (no more than 3 years prior to screening) OR within the screening phase, imaging procedures performed as per local standard) i. evidence of hepatic steatosis >5% measured by the MRI-PDFF) or assessed as moderate to severe steatosis (raised echogenicity of the liver parenchyma) by ultrasound AND ii. evidence of liver fibrosis defined as mean stiffness > 3.64 kPa as measured by the MRE protocol or mean stiffness > 7.2 kPa as measured by ultrasound based transient elastography (Fibroscan®)
• Increased ALT defined as a. ALT >1.5 ULN at screening and ALT >1.25 ULN in a local lab within 1 week to 3 months prior screening OR b. Historic ALT > 1.25 ULN more than 3 months prior to screening and two consecutive ALT > 1.5xULN must be confirmed at least 1 week apart within the screening period
• Age ≥ 18 and ≤75 years at screening
• BMI ≥25kg/m2 and 210g/week in males and >140g/week in females on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on investigator judgement.
• Prior participation in an interventional NASH trial 6 months before baseline or 5 times halflife of the investigational drug, whichever is longer.
• Prior or planned bariatric surgery during study conduct, except gastric-band surgery more than 2 years prior to screening (including adjustments) with a stable body weight within the last 12 months.
• Use of drugs historically associated with liver injury, hepatic steatosis or steatohepatitis in the 4 weeks prior to screening.
• History of liver cirrhosis (fibrosis stage 4), or hepatic decompensation (e.g. ascites, hepatic encephalopathy, variceal bleeding, etc.) or history of other forms of chronic liver disease (for example Hepatitis B, Hepatitis C, autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilsons disease, hemochromatosis, A1At deficiency, history of liver transplantation).
• Active known chronic or relevant acute infections, such as HIV (Human Immunodeficiency Virus), \viral hepatitis, or tuberculosis. QuantiFERON® TB test and HBs Ag test will be performed during screening. Patients with a positive test result may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active infection.
• Solid liver lesions other than haemangiomas.

-- Suspicion or diagnosis or history of hepatocellular carcinoma (HCC)

• eGFR 5.0 ULN at screening.
• Platelet count ULN (except for known Gilbert´s disease with a conjugated bilirubin of 450 ms, family history of long QT, or on medication prolonging QT time at screening or planned initiation during the trial.
• Any other clinical condition that, in the opinion of the investigator, would jeopardize patient safety while participating in this clinical trial.