non-alcoholic steatohepatitis MedDRA version: 22.0 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Sponsors
Boehringer Ingelheim France
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female patients = 18 years (or who are of legal age in countries where that is greater than 18 years) and = 80 years of age at time of consent. - Diagnosis of NASH (NAS = 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 defined as less than 5% self-reported change in body weight between the historical biopsy and randomization, if a historical biopsy is used. - Liver fat fraction = 8% measured by MRI-PDFF and liver stiffness > 6.0 kPa measured by FibroScan® at screening visit (if biopsy is scheduled during the screening period MRI-PDFF and FibroScan® assessments have to be performed prior to the biopsy). - 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. 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 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 64
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 (e.g. viral hepatitis, autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilson’s disease, hemochromatosis, A1At deficiency, history of liver transplantation). Hepatitis B and C testing will be done at visit 1. - 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 Visit 1. - 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 Visit 1. - Known history of HIV (Human Immunodeficiency Virus) infection and/or tuberculosis and/or an acute COVID-19 infection at Visit 1 (confirmed by SARS CoV-2 RT-PCR test). - Diagnosis of a serious or unstable disease including hepatic (other than NASH), renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease and other conditions that, in the clinical judgment of the Investigator, are likely to interfere with the analyses of safety and efficacy in this trial. Patients with a history of organ transplantation except for corneal transplantation and patients with an expected life expectancy of less than 2 years are also excluded. Further criteria apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This trial will characterize the dose response curve for BI 456906 in patients with NASH (NAS = 4, fibrosis F1-F3) by assessing three doses and placebo. The response is the proportion of patients with improvement from baseline in liver histological findings after 48 weeks.;Secondary Objective: Not applicable;Primary end point(s): 1) Improvement in liver histological findings;Timepoint(s) of evaluation of this end point: 1) week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) 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) 2) Absolute and relative change of liver fat content from baseline after 48 weeks of treatment assessed by MRI-PDFF 3) Improvement of fibrosis (yes/ no) defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment assessed by liver biopsy 4) Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy;Timepoint(s) of evaluation of this end point: 1) week 48 2) week 48 3) week 48 4) week 48 | — |
Countries
Australia, Austria, Belgium, Canada, China, Czechia, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, New Zealand, Poland, Portugal, Singapore, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactCT Disclosure & Data Transparency
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed