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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-001987-31 | EudraCT Number |
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| Name | Class |
|---|---|
| Boehringer Ingelheim | INDUSTRY |
| German Center for Diabetes Research | OTHER |
| Federal Ministry of Health, Germany | OTHER_GOV |
| Ministry of Innovation, Science and Research in North Rhine-Westphalia |
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The aim of this multicentre, prospective, placebo-controlled, double-blind, randomized, 3-arm parallel group, interventional study is to assess for the first time the effects of either a combined therapy with the antihyperglycemic drugs semaglutide and empagliflozin or empagliflozin monotherapy compared to placebo as potential treatments for non-alcoholic steatohepatitis (NASH) in patients with type 2 diabetes.
Obesity and type 2 diabetes (T2D) are tightly associated with non-alcoholic fatty liver disease (NAFLD), which in turn predicts the development of T2D and cardiovascular disease.
Up to 80% of NAFLD patients with T2D have NASH and the presence of T2D is an independent risk factor for more-advanced fibrosis, higher rate of fibrosis progression, and increased mortality. Liver-related mortality is increased 10-fold in NASH patients compared with the general population. In addition, people with NASH are at an excessive risk of cardiovascular morbidity and mortality.
Currently, there are no established pharmacotherapies for NASH patients with T2D.
The aim of this trial is to evaluate efficacy of a combined treatment with semaglutide 1 mg/week (GLP1RA) and empagliflozin 10 mg/d (SGLT2I) or ii) empagliflozin 10 mg/d monotherapy by means of histological resolution of NASH in T2D patients without progression of fibrosis after 48 weeks treatment.
To confirm a histological diagnosis of NASH and proof efficacy of treatment, a liver biopsy will be performed prior to screening as well as at the end of treatment phase.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combined treatment with Empagliflozin and Semaglutide | Experimental | Combined treatment with Empagliflozin, film-coated tablet, 10mg once daily and Semaglutide, colourless solution in pre-filled pen, 1mg once weekly |
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| Empagliflozin monotherapy | Experimental | Empagliflozin, film-coated tablet, 10mg once daily and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly) |
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| Placebo | Placebo Comparator | Placebo matching Empagliflozin (film-coated tablet, once daily) and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector | Drug | Measurement of the effect of the combined treatment with semaglutide 1mg/week and empagliflozin 10 mg/d compared to matching placebo after 48-week treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Histological resolution of NASH without worsening of fibrosis | NAFLD status will be assessed by histologic evaluation of liver biopsy samples based on NAFLD activity score. NASH resolution is defined by disappearance of ballooning (score 0), together with either disappearance of lobular inflammation or the persistence of mild lobular inflammation only (score 0 or 1) and resulting in an overall pathologic diagnosis of either steatosis alone or steatosis with mild inflammation; with no worsening of fibrosis. Worsening of fibrosis is defined by an increase of at least one stage of the Kleiner fibrosis classification. | from baseline to 48 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Overall NAFLD activity score (NAS) | Sum of a) steatosis (0-3 points), b) lobular inflammation (scored 0-3 points), c) hepatocellular ballooning (scored 0-2 points) assessed by liver histology | from baseline to 48 weeks |
| Stage of fibrosis according to the Kleiner Fibrosis Classification |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Roden, Prof., MD | German Diabetes Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medizinische Universität Graz | Graz | 8010 | Austria | |||
| Medizinische Universität Innsbruck |
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| Novo Nordisk A/S | INDUSTRY |
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double-blind placebo-controlled
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| Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide | Drug | Measurement of the effect of empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment. |
|
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| Placebo matching empagliflozin and placebo pen injector matching semaglutide | Drug | Measurement of the effect of the combined treatment with semaglutide 1mg/week and empagliflozin 10 mg/d OR empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment. |
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Assessed by liver histology according to the Kleiner Fibrosis Classification (stages 0-4) |
| from baseline to 48 weeks |
| Activity component of NASH according to the steatosis-activity-fibrosis (SAF) score | Sum of lobular inflammation (scored 0-3 points)and hepatocellular ballooning (scored 0-2 points) assessed by liver histology | from baseline to 48 weeks |
| Hepatic steatosis grade | steatosis grade (0-3) assessed by liver histology | from baseline to 48 weeks |
| Innsbruck |
| Austria |
| Wiener Gesundheitsverbund, Klinik Landstraße | Vienna | 1030 | Austria |
| Medizinische Universität Wien | Vienna | Austria |
| Wiener Gesundheitsverbund, Klinik Hietzing | Vienna | Austria |
| German Diabetes Center | Düsseldorf | North Rhine-Westphalia | 40225 | Germany |
| Herz- und Diabeteszentrum NRW | Bad Oeynhausen | 32545 | Germany |
| Franziskus-Krankenhaus Berlin | Berlin | 10787 | Germany |
| Leber- und Studienzentrum Checkpoint | Berlin | 10961 | Germany |
| University Clinics Berlin Charité | Berlin | 12200 | Germany |
| University Clinics Berlin Charité | Berlin | 13353 | Germany |
| University Clinics Bochum | Bochum | 44892 | Germany |
| Städtisches Klinikum Brandenburg GmbH | Brandenburg | 14770 | Germany |
| Städtisches Klinikum Braunschweig gGmbH | Braunschweig | 38126 | Germany |
| University Clinics Carl Gustav Carus Dresden | Dresden | 01307 | Germany |
| Universitätsklinikum Düsseldorf | Düsseldorf | 40225 | Germany |
| University Clinics Essen | Essen | 45147 | Germany |
| University Clinics Frankfurt | Frankfurt | 60590 | Germany |
| University Clinics Freiburg | Freiburg im Breisgau | 79106 | Germany |
| University Clinics Heidelberg | Heidelberg | 69120 | Germany |
| Eugastro GmbH | Leipzig | 04103 | Germany |
| University Clinics Johannes-Gutenberg Mainz | Mainz | 55131 | Germany |
| TUM | München | 81675 | Germany |
| University Clinics Tübingen | Tübingen | 72076 | Germany |
| Universitätsklinikum Ulm | Ulm | 89081 | Germany |
| University Clinics Würzburg | Würzburg | 97080 | Germany |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D065626 | Non-alcoholic Fatty Liver Disease |
| D005234 | Fatty Liver |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C570240 | empagliflozin |
| D013607 | Tablets |
| C000591245 | semaglutide |
| ID | Term |
|---|---|
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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