NASH (niet alcoholische steatose hepatitis) Non alcoholic liver inflammation Non alcoholic steatohepatitis
Conditions
Interventions
Multiple doses of BI 1467335 and/or Placebo to match BI 1467335 will be
administered.
For details, refer to protocol section 4.1.1. - 4.1.4.
NASH
Sponsors
Boehringer Ingelheim
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. 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) i. evidence of hepatic steatosis > 5% measured by the MRI-PDFF protocol ) or assessed as moderate to severe steatosis (raised echogenicity) 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®);;2. ALT > 1.5 ULN at screening and ALT > 1.25 ULN in a local lab within 1 week to 3 months prior screening;;3. Age * 18 and *75 years at screening;;4. BMI *25kg/m2 and
Exclusion criteria
Exclusion criteria: 1. Current or history of significant alcohol consumption (defined as intake of >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. ;2. Prior participation in an interventional NASH trial 6 months before baseline or 5 times halflife of the investigational drug, whichever is longer. ;3. 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. ;4. Use of drugs historically associated with liver injury, hepatic steatosis or steatohepatitis in the 4 weeks prior to screening;5. 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).;6. 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.;7. Solid liver lesions other than haemangiomas. a. Suspicion or diagnosis or history of hepatocellular carcinoma (HCC) ;8. eGFR 5.0 ULN at screening. ;10. Platelet count
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the plasma amine oxidase copper-containing 3 (AOC3) activity relative to baseline in %, 24 h post dose, after 12 weeks of treatment. The baseline is defined as the last AOC3 activity measurement prior to administration of any randomised study medication. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety and tolerability will be assessed based on the number (%) of subjects with adverse reactions. The secondary biomarker endpoints will be assessed based on the: - relative ALT change from baseline after 12 weeks of treatment - relative AST change from baseline after 12 weeks of treatment - relative AP change from baseline after 12 weeks of treatment - relative gamma-GT change from baseline after 12 weeks of treatment - relative caspase cleaved cytokeratin 18 (M30) change from baseline after 12 weeks of treatment - relative total cytokeratin 18 (M65) change from baseline after 12 weeks of treatment | — |
Countries
Belgium, Canada, France, Germany, Netherlands, Spain, United Kingdom, United States of America
Outcome results
None listed