A multi-centre, double-blind, parallel-group, randomised, placebo controlled phase II a study to investigate safety, tolerability, pharmacodynamics, and harmacokinetics of different doses of orally administered BI 1467335 during a 12-week treatment period compared to placebo in patients with clinical evidence of NASH.

Phase 2

Completed

Conditions: ASH (niet alcoholische steatose hepatitis)
Non alcoholic liver inflammation
Non alcoholic steatohepatitis
10019654

Registration Number: NL-OMON47669

Lead Sponsor: Boehringer Ingelheim

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 2

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 < 45kg/m2 at screening;;5. Stable body weight defined as less than 5% change in body weight in the 3 months prior to screening while being treated with the standard of care site and not treated with anti-obesity medication at screening;;6. Treatment with Antidiabetic concomitant medication including any insulin regimen needs to be stable for 3 months and treatment with vitamin E needs to be stable for 6 months prior to informed consent and expected to be stable throughout the trial. All other concomitant medication has to be stable for at least 4 weeks prior screening. Concomitant medications taken to treat acute conditions (e.g. headache, sinusitis) for a short period (< 7 days) are permissible, if not otherwise prohibited. For restricted medications please refer to section 4.2.2.1;;Further criteria apply, see protocol section 3.3.2.

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 <60ml/min/1.73m2 at screening (CKD-EPI formula). ;9. ALT >5.0 ULN at screening. ;10. Platelet count <150.000/*L ;Further criteria apply, see protocol section 3.3.3.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint is the plasma amine oxidase copper-containing 3 (AOC3)<br /><br>activity relative to baseline in %, 24 h post dose, after 12 weeks of<br /><br>treatment. The baseline is defined as the last AOC3 activity measurement prior<br /><br>to administration of any randomised study medication.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Safety and tolerability will be assessed based on the number (%) of subjects<br /><br>with adverse reactions.<br /><br><br /><br>The secondary biomarker endpoints will be assessed based on the:<br /><br>- relative ALT change from baseline after 12 weeks of treatment<br /><br>- relative AST change from baseline after 12 weeks of treatment<br /><br>- relative AP change from baseline after 12 weeks of treatment<br /><br>- relative gamma-GT change from baseline after 12 weeks of treatment<br /><br>- relative caspase cleaved cytokeratin 18 (M30) change from baseline after 12<br /><br>weeks of treatment<br /><br>- relative total cytokeratin 18 (M65) change from baseline after 12 weeks of<br /><br>treatment</p><br>