non alcoholic liver infammation non alcoholic steatohepatitis
Conditions
Interventions
48 weeks of treatment consisting of up to 24 weeks dose escalation period and
at least 24 weeks maintenance period.
- 60 patients on BI 456906 2.4 mg (Group 1)
- 60 patients on BI 456906 4.8 mg (Grou
Sponsors
Boehringer Ingelheim
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Male or female patients >= 18 years and = 4, with at least 1 point in inflammation and ballooning each) and fibrosis stage F1-F3 proven by a biopsy conducted during the screening period or by a historical biopsy conducted within the last 6 months prior to randomization and stable body weight between the historical biopsy and randomization. - Liver fat fraction >= 8% measured by MRI-PDFF and liver stiffness > 6.0 kPa measured by FibroScan® at visit 1. However, the diagnosis of NASH and fibrosis at liver biopsy (including historical biopsy) is the primary assessment to establish patient eligibility. - Patients willing and able to undergo liver biopsies per protocol as judged by the Investigator. - BMI >= 25 kg/m2 and a body weight >= 70 kg at visit 1. - Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. - Women of childbearing potential (WOCBP) must be willing and able to use two forms of effective contraception where at least one form is highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
Exclusion criteria
Exclusion criteria: - Current or history of significant alcohol consumption (defined as intake of > 210 g/ week in males and > 140 g/ 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 within the last 5 years. - Intake of medications historically associated with liver injury, hepatic steatosis or steatohepatitis within 12 weeks prior to visit 1. Intake of restricted medications or any medications considered likely to interfere with the safe conduct of the trial - History of other forms of chronic liver disease. Hepatitis B and C testing will be done at visit 1. Patients with positive HBsAg should be excluded. - Suspicion, diagnosis or history of hepatocellular carcinoma (HCC), or any documented active or suspected malignancy or history of malignancy with in 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix. - Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, manifest hypo- or hyperthyroidism at screening visit. - History of chronic or acute pancreatitis or elevation of serum lipase/amylase > 2x ULN, or fasting serum triglyceride levels of > 500 mg/dL (> 5.65 mmol/L) at screening. - Known history of HIV (Human Immunodeficiency Virus) infection and/or tuberculosis and/or acute COVID-19 infection at visit 1. Further criteria apply, see protocol section 3.3.3.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the improvement (yes/ no) from baseline in liver histological findings based on liver biopsy after 48 weeks of treatment in patients with NASH (NAS >= 4, fibrosis F1-F3). Also refer to protocol section 2.1.2. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Improvement of liver fat content (yes/ no) defined as at least 30% relative reduction in liver fat content after 48 weeks of treatment compared to baseline assessed by magnetic resonance imaging proton density fat fraction measurement (MRI-PDFF) - Absolute and relative change of liver fat content from baseline after 48 weeks of treatment assessed by MRI-PDFF - Improvement of fibrosis (yes/ no) defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment assessed by liver biopsy - Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy Also refer to protocol section 2.1.3. | — |
Countries
Netherlands
Outcome results
None listed