Research Article Details
| Article ID: | A06005 |
| PMID: | 33039693 |
| Source: | Contemp Clin Trials |
| Title: | Semaglutide for the treatment of non-alcoholic steatohepatitis: Trial design and comparison of non-invasive biomarkers. |
| Abstract: | Non-alcoholic steatohepatitis (NASH) is a chronic liver disease. There is a clear need to develop pharmacological treatment for patients with NASH as well as biomarkers that can diagnose the disease. We describe a trial of semaglutide treatment for NASH, identify key patient characteristics and compare the relationship of patient characteristics and non-invasive biomarkers/scores. NCT02970942 is a randomised, double-blind, placebo-controlled, multi-national Phase 2 trial of daily subcutaneous semaglutide (0.1 mg, 0.2 mg, 0.4 mg) in patients with biopsy-confirmed NASH, F1-F3 fibrosis, NAFLD Activity Score ≥ 4, and body mass index (BMI) > 25 kg/m2. Exploratory analyses were performed to evaluate correlations between baseline parameters and biomarkers in NASH. Mean (standard deviation [SD]) age of 320 randomised patients was 55 (11) years, mean BMI was 36 (6) kg/m2, and 199 (62%) had type 2 diabetes. Of the total patients, 28% had F1 fibrosis, 23% had F2 fibrosis and 49% had F3 fibrosis. The highest area under the receiver operating characteristic curve (0.69) for accuracy in classifying fibrosis stage, F2-3 versus F1, was observed for Fib-4 and Enhanced Liver Fibrosis (ELF). No substantial correlation between BMI or other clinical or biochemical parameters and fibrosis stage was observed. In this large Phase 2 trial of semaglutide treatment for NASH, the clinical profile of enrolled patients was typical for patients with NASH. Of the investigated biomarkers/scores, ELF and Fib-4 showed the most apparent correlation in classifying fibrosis stage, but had only moderate predictive value. |
| DOI: | 10.1016/j.cct.2020.106174 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D327 | Semaglutide | Chemical drug | DB13928 | GLP1R agonist | Antidiabetic drug | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D155 | Glucagon | Biological drug | DB00040 | GCGR agonist | Antidiabetic drug | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |