2023-505303-23-00招募中3 期
Multicentre, randomised, double-blind, placebo-controlled, 48-week, Phase III trial to evaluate the efficacy and safety of survodutide administered subcutaneously in participants with overweight or obesity and presumed or confirmed nonalcoholic steatohepatitis (NASH)
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 12
- 主要终点
- Relative reduction in liver fat content of at least 30% from baseline to Week 48 (yes/no) assessed by MRI-PDFF [%]
研究概览
简要总结
This trial aims to provide evidence of the efficacy, safety, and tolerability of survodutide administered once weekly as an adjunct to a reduced-calorie diet and increased physical activity, in comparison with placebo, in participants with presumed or onfirmed NASH and obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m2) with at least one of the following weight-related complications (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea, cardiovascular disease or T2DM.
The primary objective is to demonstrate superiority of survodutide in:
- Reduction in liver fat content assessed by MRI-PDFF, defined as ≥30% from baseline at Week 48 (odds ratio, survodutide vs. placebo), AND
- The difference in adjusted means of relative change (%) in body weight from baseline to Week 48 (survodutide vs. placebo)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Age ≥18 years at the time of signing informed consent, and at least the legal age of consent in countries where it is >18 years
- •BMI ≥30 kg/m², OR BMI ≥27 kg/m² and at least one weight-related comorbidity at screening: • Hypertension (defined as repeated, i.e. at least 3 measurements in resting condition, SBP values of ≥140 mmHg and/or DBP values of ≥90 mmHg in the absence of antihypertensive treatment, or intake of at least 1 anti-hypertensive drug to maintain a normotensive blood pressure) • Dyslipidaemia (defined as at least 1 lipid-lowering treatment required to maintain normal blood lipid levels, or low-density lipoprotein [LDL] ≥160 mg/dL [≥4.1 mmol/L] or triglycerides ≥150 mg/dL [≥1.7 mmol/L], or high-density lipoprotein (HDL] <40 mg/dL (<1.0 mmol/L] for men or HDL<50 mg/dL (<1.3 mmol/L) for women • Obstructive sleep apnoea • Cardiovascular disease (e.g. heart failure with New York Heart Association [NYHA] functional class II-III, history of ischaemic or haemorrhagic stroke or cerebrovascular revascularisation procedure [e.g. carotid endarterectomy and/or stent], MI, coronary artery disease, or peripheral vascular disease) • T2DM (diagnosed at least 180 days prior to screening, with glycated haemoglobin [HbA1c] ≥6.5% [48 mmol/mol] and <10% [86 mmol/mol] as measured by the central laboratory at screening)
- •Presumed/confirmed NASH: Evidence of hepatic steatosis (defined by an MRIPDFF ≥8% at screening) with the exclusion of secondary causes of hepatic fat accumulation such as significant alcohol consumption, other chronic liver diseases and/or steatogenic medications, AND at least one of the following: • MRE ≥2.61 and <4.68 kPa at screening, OR • MAST score ≥0.242 at screening, when MAST score = exp(MAST)/(1+exp[MAST]), where MAST = -12.17 + 7.07 logMRE + 0.037 PDFF + 3.55 log AST OR • FAST score ≥0.5 at screening, OR • FibroScan® VCTE™ ≥8 kPa and <20 kPa at screening, OR • FIB-4 score ≥2.67 and <3.48 at screening, OR • ELF score >7.7 and <11.3 at screening, OR • cT1 ≥875 ms at screening, OR • Recent liver biopsy (within 3 years of screening) consistent with NASH (defined as the presence of steatosis, inflammation, and ballooning) with stage ≤3 fibrosis according to the NASH Clinical Research Network classification.
- •History of at least one self-reported unsuccessful dietary effort to lose body weight
排除标准
- •Current or history of significant alcohol consumption (defined as intake of >210 g/week in men and >140 g/week in women on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on the investigator’s judgement within the last 5 years.
- •Previous or planned (during the trial period) treatment for obesity with surgery or a weight loss device, or prior surgery of the GI tract that could interfere with body weight. The following are allowed: (1) liposuction and/or abdominoplasty, if performed >1 year before screening, (2) lap banding, if the band has been removed >1 year before screening, (3) intragastric balloon, if the balloon has been removed >1 year before screening, (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed >1 year before screening (5) appendectomy, (6) simple hernia repair, or (7) cholecystectomy.
- •Obesity induced by other endocrinologic disorders (i.e. Cushing Syndrome) or diagnosed monogenetic or syndromic forms of obesity (i.e. melanocortin 4 receptor deficiency, leptin deficiency, or Prader Willi Syndrome)
- •Intake of medications associated with liver injury, hepatic steatosis or steatohepatitis
- •History of other chronic liver diseases (e.g. viral hepatitis, autoimmune liver disease, primary biliary cholangitis , primary sclerosing cholangitis, Wilson’s disease, hemochromatosis, A1At deficiency, history of liver transplantation). Hepatitis B and C testing will be done at Visit
- •Participants with positive HBsAg should be excluded. Participants treated for hepatitis C must have a negative RNA test at screening and also be HCV RNA negative for at least 3 years prior to screening in order to be eligible for the trial. Trial patients with positive HCV antibody and no history of HCV treatment require a negative HCV RNA test at screening to be eligible for the trial.
- •Cirrhosis based on clinical assessment, abdominal imaging, liver histology or noninvasive tests assessed at screening (ELF ≥11.3, FIB4 ≥3.48, FibroScan® VCTE™ ≥20 kPa, or MRE ≥4.68 kPa), or history of cirrhosis.
- •Current decompensated liver disease or previous hepatic decompensation (ascites, spontaneous bacterial peritonitis, portal hypertension bleeding, hepatic encephalopathy, hepatorenal syndrome).
- •Previous or current evidence of portal hypertension (e.g. splenomegaly, oesophageal varices, or other portosystemic collateral pathways).
- •Any of the following liver laboratory test abnormalities at screening: • Serum AST and/or ALT elevation ≥5x ULN • Total serum bilirubin concentration ≥1.2x ULN (except for cases of known Gilbert’s Syndrome) • Alkaline phosphatase >2x ULN • INR ≥1.3 (unless patient is on anticoagulants)
- •Body weight variation (self-reported) >5% within 3 months before screening
- •Medications for obesity within 3 months before screening
结局指标
主要结局
Relative reduction in liver fat content of at least 30% from baseline to Week 48 (yes/no) assessed by MRI-PDFF [%]
Relative reduction in liver fat content of at least 30% from baseline to Week 48 (yes/no) assessed by MRI-PDFF [%]
Relative change (%) in body weight [kg] from baseline to Week 48
Relative change (%) in body weight [kg] from baseline to Week 48
次要结局
- Absolute change from baseline to Week 48 in liver fat content assessed by MRI-PDFF [%]
- Reduction from baseline to Week 48 in cT1 [ms] levels of ≥80 ms (yes/no)
- Absolute and relative change from baseline to Week 48 in ALT [U/L] levels
- Absolute and relative change from baseline to Week 48 in HOMA-IR (FPI [mlU/L]·FPG [mmol/L]/22.5)
- Absolute and relative change from baseline to Week 48 in liver stiffness [kPa] assessed by MRE
- Absolute and relative change in liver volume [mL] from baseline to Week 48 measured using MRI
- Absolute and relative change from baseline to Week 48 in waist circumference [cm]
- Relative change (%) from baseline to Week 48 in liver fat content assessed by MRI-PDFF [%]
研究者
CT Disclosure & Data Transparency
Scientific
Boehringer Ingelheim International GmbH
研究点 (12)
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