Different doses of BI 1467335 compared to placebo in patients with clinical evidence of NASH
- Conditions
- on-alcoholic steatohepatitisMedDRA version: 20.0 Level: PT Classification code 10076331 Term: Steatohepatitis System Organ Class: 10019805 - Hepatobiliary disordersTherapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2016-000499-83-BE
- Lead Sponsor
- SCS Boehringer Ingelheim Comm. V
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 108
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) 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
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®)
2. 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 >1.5x ULN must be confirmed at least 1 week apart within the screening period
3. Age = 18 and =75 years at screening
4. BMI =25kg/m2 and <45kg/m2
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 at the study site.
6. Treatment with Antidiabetic, anti-obesity concomitant medication including any insulin regimen, and vitamin E needs to be stable for 3 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.
7. For female patients:: Women of childbearing potential* can be randomized after a negative pregnancy test and under adaquate contraception with two methods, of which at least one is highly effective, during the trial.
* A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tubal ligation is NOT a method of permanent sterilisation. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
8. Signed and dated written informed consent in accordance with GCP and local legislation prior to admission to the trial.
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 88
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1. Current or history of significant alcohol consumption (defined as intake of >210g/week in males and >140g/week 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; please refert to section 4.2.2.
5. History of liver cirrhosis (fibrosis stage 4) 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. History of HIV.
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/µL
11. Bilirubin level > ULN (except for known Gilbert´s disease with a conjugated bilirubin of < 0.3 mg/dL))
12. Uncontrolled diabetes defined as an HbA1c =9.5% in the 3 months prior to or at screening.
13. 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 study. Patients with an expected life expectancy of less than 2 years are also excluded.
14. Major surgery (major according to the investigator’s assessment) performed within 12 weeks prior to randomisation or planned during study conduct, e.g. hip replacement.
15. Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
16. Patients who must or wish to continue the intake of restricted medications (see section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the trial.
17. Previous randomisation in this trial.
18. Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s).
19. Chronic drug abuse or any condition that, in the investigator’s opinion, makes them an unreliable study subject or unlikely to complete the trial.
20. Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
21. Patients with Wolff-Parkinson-White Syndrom
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is the proof of mechanism and support of dose finding, together with the safety evaluation in patients with clinical evidence of NASH. ;Secondary Objective: Effect of BI 1467335 on reduction of secondary biomarker endpoints (ALT, AST, AP, Gamma-GT and CK18 fragments). Safety will be assessed throughout the study to provide key information regarding the use of BI 1467335 in patients with NASH.;Primary end point(s): 1) Plasma amine oxidase copper-containing 3 (AOC3) activity relative to baseline in %, 24 h post dose, after 12 weeks of treatment.;<br> Timepoint(s) of evaluation of this end point: 1) 24 hours <br>
- Secondary Outcome Measures
Name Time Method <br> Timepoint(s) of evaluation of this end point: 1) 16 weeks <br> 2) 12 weeks <br> 3) 12 weeks <br> 4) 12 weeks<br> 5) 12 weeks <br> 6) 12 weeks <br> 7) 12 weeks<br> ;<br> Secondary end point(s): 1) Percentage of subjects with adverse reactions. <br> 2) relative ALT change from baseline <br> 3) relative AST change from baseline <br> 4) relative AP change from baseline <br> 5) relative Gamma-GT change from baseline <br> 6) relative caspase cleaved cytokeratin 18 (M30) change from baseline <br> 7) relative total cytokeratin 18 (M65) change from baseline<br>