Investigation of efficacy and safety of three dose levels of subcutaneous semaglutide once daily versus placebo in subjects with non-alcoholic steatohepatitis.
- Conditions
- on-alcoholic steatohepatitisMedDRA version: 22.0Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disordersTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2016-000685-39-NL
- Lead Sponsor
- ovo Nordisk A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 288
1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial, except for protocol described pre-screening activities which require a separate informed consent.
2. Male or female, aged 18-75 years (both inclusive) (for Japan: male or female aged 20-75 years (both inclusive) at the time of signing informed consent.
3. Histologic evidence of NASH based on central pathologist evaluation of a liver biopsy obtained up to 21 weeks before screening.
4. A histological NAS > = 4 with a score of 1 or more in each sub-component of the score based on central pathologist evaluation.
5. NASH fibrosis stage 1, 2 or 3 according to the NASH CRN fibrosis staging system based on central pathologist evaluation.
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 245
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 43
1. Known or suspected abuse of alcohol (> 20 g/day for women or > 30 g/day for men), alcohol dependence* or narcotics. (* = assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)).
2. Diagnosis of type 1 diabetes according to medical records.
3. HbA1c > 10% at screening.
4. History or presence of pancreatitis (acute or chronic).
5. Calcitonin = 50 ng/L at screening.
6. Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative.
7. Body Mass Index (BMI) = 25.0 kg/sqm at the screening visit (visit 1).
8. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the effect of semaglutide subcutaneous (s.c.) once daily versus placebo on histological resolution of non-alcoholic steatohepatitis (NASH).;Secondary Objective: 1. To investigate the dose-response relationship of three dose levels of semaglutide s.c. once daily (0.1 mg/day, 0.2 mg/day and 0.4 mg/day) on histological resolution of NASH.<br>2. To compare the effects of semaglutide s.c. once daily to placebo on liver-related histological parameters and biomarkers of NASH disease.<br>;Primary end point(s): NASH resolution without worsening of fibrosis (yes/no);Timepoint(s) of evaluation of this end point: After 72 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. At least one stage of liver fibrosis improvement with no worsening of NASH (yes/no) (worsening defined as an increase of at least one stage of either lobular inflammation or hepatocyte ballooning according to NASH clinical research network (CRN) criteria).<br>2. Change in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) (0-8)<br>3. Change in stage of fibrosis according to the Kleiner fibrosis classification (0-4)<br>4. Change in activity component of steatosis-activity-fibrosis (SAF) score (0-4)<br>5. Change in fasting plasma glucose (FPG)<br>6. Change in glycosylated haemoglobin A1c (HbA1c)<br>7. Change in serum enhanced liver fibrosis (ELF)<br>;Timepoint(s) of evaluation of this end point: 1. After 72 weeks <br>2. – 7. From baseline to week 72<br>