Investigation of Efficacy and Safety of Semaglutide s.c. Once-weekly Versus Placebo in Subjects With Non-alcoholic Steatohepatitis and Compensated Liver Cirrhosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 71
- 试验地点
- 38
- 主要终点
- Percentage of Participants With At Least One Stage of Liver Fibrosis Improvement With No Worsening of Non-Alcoholic Steatohepatitis (NASH) After 48 Weeks
研究概览
简要总结
Semaglutide is a medicine studied in patients with non-alcoholic steatohepatitis (NASH), as it may improve liver damage. Participants will either get semaglutide or placebo (a dummy medicine) - which treatment participants get is decided by chance. The study will last for about 61 weeks in total. Participants will have 10 clinic visits and 3 phone calls with the study doctor or staff during the study. Some of the clinic visits may be spread over more days. Participants will need to inject themselves with medicine under the skin. Participants will have to do this once a week for 48 weeks. The study includes magnetic resonance imaging (MRI) scans of the liver, 1 or 2 liver tissue samples, ultrasound scans of the stomach and a possible examination of the food pipe. For some tests participants may need to remove some items of clothing. Participants will stop in the study if the doctor thinks that there are any risks for their health. The information collected from participants during the study may help them and other patients with NASH in the future. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent.
- •Histologic evidence of NASH and fibrosis stage 4 according to the NASH CRN classification based on central pathologist evaluation of a liver biopsy obtained within 360 days prior to screening. In subjects who have never had a liver biopsy showing NASH and F4, liver stiffness above 14 kPa by FibroScan® at screening must be documented before subjects can have a trial-related liver biopsy
- •A histological NAFLD activity score (NAS) equal to or above 3 with a score of 1 or more in lobular inflammation and hepatocyte ballooning based on central pathologist evaluation
- •Body mass index equal to or above 27 kg/m^2
排除标准
- •Presence or history of hepatic decompensation (e.g. ascites, variceal bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis) or liver transplantation
- •Presence or history of gastroesophageal varices within the past 360 days prior to screening. For subjects with no known history of gastroesophageal varices and with a Fibroscan® equal to or above 20 kPa and thrombocytes equal to or below 150,000, a esophagogastroduodenoscopy must be performed to evaluate presence of gastroesophageal varices
- •Presence or history of hepatocellular carcinoma
- •Treatment with vitamin E (at doses equal to or above 800 IU/day) or pioglitazone which has not been at a stable dose in the opinion of the investigator in the period from 90 days prior to screening
- •Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the period from 90 days prior to screening
- •Treatment with other glucose lowering agent(s) (apart from what is listed in the exclusion criterion above) or weight loss medication not stable in the opinion of the investigator in the period from 28 days prior to screening
研究组 & 干预措施
Semaglutide
Dose escalation to 2.4 mg of semaglutide once-weekly
干预措施: Semaglutide (Drug)
Placebo
Semaglutide placebo once-weekly
干预措施: Placebo (semaglutide) (Drug)
结局指标
主要结局
Percentage of Participants With At Least One Stage of Liver Fibrosis Improvement With No Worsening of Non-Alcoholic Steatohepatitis (NASH) After 48 Weeks
时间窗: Week 48
NASH resolution defined by NASH clinical research network (CRN) as lobular inflammation of 0 or 1; hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, higher scores indicating more severe hepatocellular ballooning/lobular inflammation. Worsening of NASH defined by NASH CRN as increase of at least 1 stage of either lobular inflammation, hepatocyte ballooning or steatosis. Worsening of fibrosis defined by increase in fibrosis at least 1 stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
次要结局
- Change From Baseline in Liver Fat Content Measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Liver Stiffness Measured by Magnetic Resonance Elastography (MRE)-Ratio to Baseline(Baseline (week 0), Week 48)
- Percentage of Participants With NASH Resolution After 48 Weeks(Week 48)
- Change From Baseline in Fibrosis-4 Score-Ratio to Baseline(Baseline (week 0), Week 48)
- Percentage of Participants With Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)(Baseline (week 0), Week 48)
- Percentage of Participants With Change in Steatosis(Baseline (week 0), Week 48)
- Percentage of Participants With Change in The Fibrosis Stage According to The Kleiner Fibrosis Classification(Baseline (week 0), Week 48)
- Percentage of Participants With Change in Hepatocyte Ballooning(Baseline (week 0), Week 48)
- Percentage of Participants With Change in Lobular Inflammation(Baseline (week 0), Week 48)
- Percentage of Participants With Change in The Steatosis-Activity-Fibrosis (SAF) Activity Component Score(Baseline (week 0), Week 48)
- Change From Baseline in Hepatic Collagen(Baseline (week 0), Week 48)
- Percentage of Participants With Improvement in Steatosis (Yes/No)(Baseline (week 0), Week 48)
- Percentage of Participants With Improvement in NAS (Yes/No)(Baseline (week 0), Week 48)
- Percentage of Participants With Improvement in SAF Activity Component Score (Yes/No)(Baseline (week 0), Week 48)
- Percentage of Participants With Improvement in Ishak Fibrosis Score (Yes/No)(Baseline (week 0), Week 48)
- Change From Baseline in Body Weight(Baseline (week 0), Week 48)
- Percentage of Participants With Change in The Ishak Fibrosis Score(Baseline (week 0), Week 48)
- Percentage of Participants With Improvement in Fibrosis Stage According to The Kleiner Fibrosis Classification (Yes/No)(Baseline (week 0), Week 48)
- Percentage of Participants With Improvement in Hepatocyte Ballooning (Yes/No)(Baseline (week 0), Week 48)
- Percentage of Participants With Improvement in Lobular Inflammation (Yes/No)(Baseline (week 0), Week 48)
- Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c)(Baseline (week 0), Week 48)
- Change From Baseline in Fasting Plasma Glucose (FPG)(Baseline (week 0), Week 48)
- Change From Baseline in Fasting C-peptide-Ratio to Baseline(Baseline (week 0), Week 48)
- Relative Change From Baseline in Body Weight(Baseline (week 0), Week 48)
- Change From Baseline in Waist Circumference(Baseline (week 0), Week 48)
- Change From Baseline in Body Mass Index (BMI)(Baseline (week 0), Week 48)
- Percentage of Participants With Weight Loss of >= 5% of Baseline Body Weight at Week 48(Week 48)
- Percentage of Participants With Weight Loss of >= 10% of Baseline Body Weight at Week 48(Week 48)
- Change From Baseline in Systolic And Diastolic Blood Pressure(Baseline (week 0), Week 48)
- Change From Baseline in Total Cholesterol-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Triglycerides-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Free Fatty Acids (FFA)-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Alanine Aminotransferase (ALT)-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Aspartate Aminotransferase (AST)-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Gamma-Glutamyl Transferase (GGT)-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Albumin-Ratio to Baseline(Baseline (week 0), Week 48)
- Changes From Baseline in Thrombocytes-Ratio to Baseline(Baseline (week 0), Week 48)
- Number of Treatment-Emergent Adverse Events (TEAEs)(From baseline (week 0) to week 55)
- Change From Baseline in International Normalized Ratio (INR)-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Direct Bilirubin-Ratio to Baseline(Baseline (week 0), Week 48)
- Change From Baseline in Total Bilirubin-Ratio to Baseline(Baseline (week 0), Week 48)
- Number of Treatment-Emergent Hypoglycaemic Episodes(From baseline (week 0) to week 55)
- Change From Baseline in Pulse(Baseline (week 0), Week 48)