NCT02970942已完成2 期
This Trial is Conducted Globally. The Aim of This Trial is to Investigate Efficacy and Safety of Three Dose Levels of Subcutaneous Semaglutide Once Daily Versus Placebo in Subjects With Non-alcoholic Steatohepatitis
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 320
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Non- Alcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 72 Weeks (Yes/No)
研究概览
简要总结
Investigation of efficacy and safety of three dose levels of subcutaneous semaglutide once daily versus placebo in subjects with non-alcoholic steatohepatitis
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
- Double (Participant, Investigator)
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
- •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. - 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 - Local histological diagnosis of NASH followed by histological confirmation of NASH based on central pathologist evaluation of a liver biopsy obtained up to 21 weeks before screening - Histologic evidence of NASH based on central pathologist evaluation of a liver biopsy obtained up to 21 weeks before screening. - NASH fibrosis stage 1, 2 or 3 according to the NASH CRN fibrosis staging system based on central pathologist evaluation
排除标准
- •Known or suspected abuse of alcohol (above 20 g/day for women or above 30 g/day for men), alcohol dependence* or narcotics. (* = assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)) - Diagnosis of type 1 diabetes according to medical records - HbA1c above 10% at screening - History or presence of pancreatitis (acute or chronic) - Calcitonin equal or above 50 ng/L at screening - Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative - Body Mass Index (BMI) ≤ 25.0 kg/sqm at the screening visit (visit 1) - 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)
研究组 & 干预措施
Placebo 2
Placebo Comparator
干预措施: Placebo (Drug)
Semaglutide 0,1 mg
Experimental
干预措施: Semaglutide (Drug)
Semaglutide 0,2 mg
Experimental
干预措施: Semaglutide (Drug)
Semaglutide 0,4 mg
Experimental
干预措施: Semaglutide (Drug)
Placebo 1
Placebo Comparator
干预措施: Placebo (Drug)
Placebo 3
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Non- Alcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 72 Weeks (Yes/No)
时间窗: After 72 weeks
NASH resolution defined by NASH clinical research network as lobular inflammation of 0 or 1 and hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation. Worsening of fibrosis defined by an increase in fibrosis at least one stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Endpoint 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 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
次要结局
- Percentage of Participants With at Least One Stage of Liver Fibrosis Improvement With no Worsening of NASH After 72 Weeks (Yes/No)(After 72 weeks)
- Percentage of Participants With Change in Total NAFLD (Non- Alcoholic Fatty Liver Disease) Activity Score (NAS)(Baseline (week 0), Week 72)
- Percentage of Participants With Change in Steatosis(Baseline (week 0), Week 72)
- Percentage of Participants With Change in Lobular Inflammation(Baseline (week 0), Week 72)
- Percentage of Participants With Change in Hepatocyte Ballooning(Baseline (week 0), Week 72)
- Percentage of Participants With Change in Fibrosis Stage According to the Kleiner Fibrosis Classification(Baseline (week 0), Week 72)
- Change in Cytokeratin 18 (CK-18) Fragments(Baseline (week 0), Week 72)
- Percentage of Participants With Change in Activity Component of Steatosis-activity-fibrosis (SAF) Score(Baseline (week 0), Week 72)
- Change in Fibrosis-4 Score(Baseline (week 0), Week 72)
- Change in NAFLD Fibrosis Score (NFS)(Baseline (week 0), Week 72)
- Change in Alanine Aminotransferase (ALT)(Baseline (week 0), Week 72)
- Change in Aspartate Aminotransferase (AST)(Baseline (week 0), Week 72)
- Change in Gamma Glutamyl Transferase (GGT)(Baseline (week 0), Week 72)
- Change in Albumin(Baseline (week 0), Week 72)
- Change in International Normalized Ratio (INR)(Baseline (week 0), Week 72)
- Change in Enhanced Liver Fibrosis (ELF)(Baseline (week 0), Week 72)
- Change in microRNA 122 (miR-122)(Baseline (week 0), Week 72)
- Change in Monocyte Chemoattractant Protein 1 (MCP-1)(Baseline (week 0), Week 72)
- Change in Fasting Plasma Glucose (FPG)(Baseline (week 0), Week 72)
- Change in Homeostatic Model Assessment - Insulin Resistance (HOMA-IR)(Baseline (week 0), Week 72)
- Change in Pulse From Baseline to Week 72(Baseline (week 0), Week 72)
- Percentage of Participants With Change in Electrocardiogram (ECG)(Baseline (week 0), Week 72)
- Percentage of Participants With Change in Physical Examination: Cardiovascular System(Week -6, week 72)
- Percentage of Participants With Change in Physical Examination: Central and Peripheral Nervous System(Week -6, week 72)
- Percentage of Participants With Change in Physical Examination: Gastrointestinal System Including Mouth(Week -6, week 72)
- Percentage of Participants With Change in Physical Examination: General Appearance(Week -6, week 72)
- Change in Interleukin-1 Receptor (IL-1R) Antagonist(Baseline (week 0), Week 72)
- Change in Liver Stiffness Assessed by FibroScan®(Baseline (week 0), Week 72)
- Percentage of Participants With Weight Loss of ≥ 10% of Baseline Body Weight at 72 Weeks (Yes/No)(Week 72)
- Change in Body Weight(Baseline (week 0), Week 72)
- Change in Waist Circumference(Baseline (week 0), Week 72)
- Change in Fibroblast Growth Factor 21 (FGF-21)(Baseline (week 0), Week 72)
- Change in Liver Steatosis Assessed by FibroScan®(Baseline (week 0), Week 72)
- Change in Glycosylated Haemoglobin (HbA1c) (%-Point)(Baseline (week 0), Week 72)
- Percentage of Participants With Weight Loss of ≥ 5% of Baseline Body Weight at 72 Weeks (Yes/No)(Week 72)
- Change in Body Mass Index (BMI)(Baseline (week 0), Week 72)
- Change in HbA1c (Millimoles Per Mole)(Baseline (week 0), Week 72)
- Change in Fasting Glucagon(Baseline (week 0), Week 72)
- Change in Diastolic Blood Pressure (DBP)(Baseline (week 0), Week 72)
- Change in Systolic Blood Pressure (SBP)(Baseline (week 0), Week 72)
- Change in Free Fatty Acids(Baseline (week 0), Week 72)
- Change in Total Cholesterol(Baseline (week 0), Week 72)
- Change in Low Density Lipoprotein (LDL) Cholesterol(Baseline (week 0), Week 72)
- Change in High Density Lipoprotein (HDL) Cholesterol(Baseline (week 0), Week 72)
- Change in Very Low Density Lipoprotein (VLDL) Cholesterol(Baseline (week 0), Week 72)
- Change in Triglycerides(Baseline (week 0), Week 72)
- Change in High Sensitivity C-reactive Protein (hsCRP)(Baseline (week 0), Week 72)
- Change in Short Form 36 (SF-36) Score(Baseline (week 0), Week 72)
- Number of Treatment-emergent Adverse Events (TEAEs)(From week 0 to week 79)
- Number of Treatment-emergent Hypoglycaemic Episodes(From week 0 to week 79)
- Number of Treatment-emergent Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemic Episodes(From week 0 to week 79)
- Number of Treatment-emergent Severe Hypoglycaemic Episodes(From week 0 to week 79)
- Number of Participants Discontinuing Treatment Due to Gastrointestinal Adverse Events(From week 0 to week 79)
- Number of Participants With Occurrence of Anti-semaglutide Antibodies During and After 72 Weeks Treatment (Yes/No)(From week 0 to week 79)
- Number of Participants With Anti-semaglutide Antibodies With in Vitro Neutralising Effect During and After 72 Weeks Treatment (Yes/No)(From week 0 to week 79)
- Number of Participants With Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 During and After 72 Weeks Treatment (Yes/No)(From week 0 to week 79)
- Number of Participants With Cross-reacting Anti-semaglutide Binding Antibodies With in Vitro Neutralising Effect to Native GLP-1 During and After 72 Weeks Treatment (Yes/No)(From week 0 to week 79)
- Percentage of Participants With Change in Physical Examination: Head, Ears, Eyes, Nose, Throat, Neck(Week -6, week 72)
- Percentage of Participants With Change in Physical Examination: Lymph Node Palpation(Week -6, week 72)
- Percentage of Participants With Change in Physical Examination: Musculoskeletal System(Week -6, week 72)
- Percentage of Participants With Change in Physical Examination: Respiratory System(Week -6, week 72)
- Percentage of Participants With Change in Physical Examination: Skin(Week -6, week 72)
- Percentage of Participants With Change in Physical Examination: Thyroid Gland(Week -6, week 72)
- Change in Haematocrit(Baseline (week 0), Week 72)
- Change in Haemoglobin (g/dL)(Baseline (week 0), Week 72)
- Change in Haemoglobin (mmol/L)(Baseline (week 0), Week 72)
- Change in Leukocytes(Baseline (week 0), Week 72)
- Change in Thrombocytes(Baseline (week 0), Week 72)
- Change in Erythrocytes(Baseline (week 0), Week 72)
- Change in Creatinine (mg/dL)(Baseline (week 0), Week 72)
- Change in Creatinine (Umol/L)(Baseline (week 0), Week 72)
- Change in Estimated Glomerular Filtration Rate (eGFR)(Baseline (week 0), Week 72)
- Change in Creatine Kinase(Baseline (week 0), Week 72)
- Change in Urea(Baseline (week 0), Week 72)
- Change in Total Bilirubin (mg/dL)(Baseline (week 0), Week 72)
- Change in Total Bilirubin (Umol/L)(Baseline (week 0), Week 72)
- Change in Alkaline Phosphatase(Baseline (week 0), Week 72)
- Change in Ferritin(Baseline (week 0), Week 72)
- Change in Sodium (mEq/L)(Baseline (week 0), Week 72)
- Change in Sodium (mmol/L)(Baseline (week 0), Week 72)
- Change in Potassium (mEq/L)(Baseline (week 0), Week 72)
- Change in Potassium (mmol/L)(Baseline (week 0), Week 72)
- Change in Calcium (mg/dL)(Baseline (week 0), Week 72)
- Change in Calcium (mmol/L)(Baseline (week 0), Week 72)
- Change in Amylase(Baseline (week 0), Week 72)
- Change in Lipase(Baseline (week 0), Week 72)
- Change in Calcitonin(Baseline (week 0), Week 72)
研究者
研究点 (1)
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