2023-508170-28-00已完成2 期
Effects of NNC0194-0499 alone and in combination with semaglutide, of semaglutide alone, and of cagrilintide alone and in combination with semaglutide on liver damage and alcohol use in people with alcohol-related liver disease
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 140
- 试验地点
- 44
- 主要终点
- Change in Enhanced Liver Fibrosis (ELF)
研究概览
简要总结
To investigate the efficacy of NNC0194-0499, cagrilintide, semaglutide alone and NNC0194-0499 or cagrilintide in combination with semaglutide versus placebo on liver damage and function in people with alcohol-related liver disease.
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
- 否
入选标准
- •Participants are eligible to be included in the study only if all the following criteria apply:
- •Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
- •Male or female.
- •Age 18 years or above, and at the legal drinking age according to local requirements (Section 10.16) at the time of signing the informed consent.
- •Patient-reported history of alcohol overuse for ≥5 years with an alcohol history of a mean of ≥50 grams (male)/40 grams (female) pr day for the last year leading up to the time of signing informed consent.
- •ELF ≥ 9.0 units.
排除标准
- •Liver-related exclusion criteria:
- •Treatment with GLP-1 RAs within 90 days prior to V
- •Presence of acute pancreatitis within 180 days prior to V
- •1.Documented causes of chronic liver disease other than Alcohol-related liver disease (ALD).
- •History or presence of type 1 diabetes at V
- •13.Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
- •Alcohol-related exclusion criteria:
- •14.History of seizure disorder (except childhood febrile seizures)
- •CIWA-Ar score ≥ 10
- •Mental health related exclusion criteria:
- •Active or unstable depression or other active or unstable psychiatric conditions[1] which in the investigator’s opinion can jeopardise the participant’s safety or compliance with the protocol.
- •a) ALT > 5 x ULN at V
- •AST > 5 x ULN at V
- •A history of a suicidal attempt within 5 years before screening
- •Suicidal ideation corresponding to type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at V
- •Baseline screening using Montgomery–Åsberg Depression Rating Scale (MADRS) at V2, score corresponding to ≥ 34 (severe depression).
- •2.Positive HBsAg, positive HIV-1 or HIV-2 Ab, positive HCV RNA at screening (V1) or any known presence of HCV RNA or HBsAg within 2 years of screening (V1).
- •General safety-related exclusion criteria:
- •BMI ≤ 25 kg/m
- •21.Known or suspected hypersensitivity to study intervention(s) or related products. (incl. excipients).
- •Previous participation (i.e., signed informed consent) in this study. If exclusion criteria 5, 15, 24, or 33 is met, a single rescreening is possible at the investigator’s discretion. Re-screening is also allowed if a participant has previously screen-failed on the exclusion criterion for blood pressure (criterion 33 in protocol version 1-4). Re-screening is also allowed once if a participant has previously screen failed on the inclusion criterion 5 (ELF score ≥9.8 in protocol version 1-5), if ELF score was previously ≥9.0 and <9.
- •Participation (i.e., signed informed consent) in any other interventional clinical study within 180 days before visit (V1), including any post-treatment follow-up period.
- •Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method with low user-dependence
- •b) Total bilirubin > 1.5 mg/dL at V
- •Total bilirubin level > 1.5 mg/dL is allowed if conjugated bilirubin is within normal range.
- •Presence or history of malignant neoplasms other than hepatocellular carcinoma within 5 years prior to V
- •Basal and squamous cell skin cancer and any carcinoma in situ are allowed.
- •History or presence of chronic pancreatitis at V
- •Uncontrolled thyroid disease, as assessed by the investigator.
- •Any of the following: myocardial infarction, stroke, classification of heart failure NYHA Class IV, hospitalisation for unstable angina pectoris or transient ischaemic attack within 90 days prior to V
- •3.Presence or history of ascites more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or liver transplantation at screening (V1).
- •Any participant for whom substantial weight loss might, in the investigator’s opinion, jeopardise the safety of the participant.
- •Known or suspected drug (including opioids) or chemical substance abuse (excluding alcohol) within 1 year before screening.
- •31.Any condition which might, in the investigator’s opinion, jeopardise the safety of the participant or compliance with the protocol.This includes incapacitated subjects, subjects deprived of liberty or subjects committed to an institution.
- •Treatment with medications approved for AUD within 90 days prior to V1 (i.e., naltrexone, acamprosate, disulfiram, topiramate, varenicline, or baclofen). Benzodiazepines are allowed for up to 2 weeks as rescue medication for alcohol withdrawal symptoms."
- •33 Pulse outside the range of 50-89 beats/minute at screening.
- •c) Alkaline phosphatase levels > 2 x ULN at V
- •Alcohol hepatitis at randomisation (as defined by NIAAA75)
- •Vibration Controlled Transient Elastography LSM ≥ 25 kPa at V
- •If participants meet this criterion, rescreening is allowed once.
- •Presence or history of gastro-oesophageal varices ≥ grade 2* at V
- •For participants with LSM ≥ 20 kPa as well as blood platelets count < 150,000 per µL of blood an oesophagogastroduodenoscopy performed no more than 52 weeks prior to V2 must be available at V
- •Grade 2: varices projecting by one-third of the luminal diameter that cannot be compressed with air insufflation4
- •7.Presence or history of hepatocellular carcinoma at V1
- •Any laboratory safety parameters at screening outside the below laboratory ranges, see designated reference range documents for specific values:
- •d) INR of prothrombin time ≥ 1.35 at V
- •e) MELD score > 12 points at V
- •f) eGFR < 60 mL/min/1.73 m2 as defined according to the CKD-EPI creatinine equation (CKD-EPI, 2021) at V
- •HbA1c > 80 mmol/mol (9.5%) at V
- •Platelet count < 100,000 per µL of blood at V
- 另有 2 项未显示
研究组 & 干预措施
Placebo (zalfermin) + Placebo (semaglutide)
Placebo
干预措施: Placebo (zalfermin) + Placebo (semaglutide) (Drug)
zalfermin
Test
干预措施: zalfermin (Drug)
cagrilintide semaglutide, cagrilintide semaglutide, cagrilintide semaglutide, cagrilintide semaglutide, cagrilintide semaglutide
Test
干预措施: cagrilintide semaglutide (Drug)
semaglutide
Test
干预措施: semaglutide (Drug)
cagrilintide, cagrilintide, cagrilintide, cagrilintide, cagrilintide
Test
干预措施: cagrilintide (Drug)
Placebo (cagrilintide) + placebo (semaglutide)
Placebo
干预措施: Placebo (cagrilintide) + placebo (semaglutide) (Drug)
结局指标
主要结局
Change in Enhanced Liver Fibrosis (ELF)
Change in Enhanced Liver Fibrosis (ELF)
次要结局
- Supportive secondary endpoints:
- Change in Pro-peptide of Collagen 3 (Pro-C3)
- Change in liver stiffness assessed by Vibration Controlled Transient Elastography (VCTE)
- Change in liver steatosis assessed by Controlled Attenuated Parameter (CAP)
- Change in Alanine Aminotransferase (ALT)
- Change in Aspartate Aminotransferase (AST)
- Supportive secondary endpoints to secondary objectives:
- Number of treatment-emergent adverse events
- Change in Phosphatidylethanol (PEth)
- Change in alcohol amount measured by timeline follow-back (TLFB)
- Change in total cholesterol
研究者
EU Submission Hub
Scientific
Novo Nordisk A/S
研究点 (44)
Loading locations...
相似试验
招募中
1 期
A Study Looking at How Weekly Injections of Two Hormones - GIP and Amylin - Affect Stomach-related Side Effects in People Who Are Overweight or ObeseNCT07411560Novo Nordisk A/S100
已完成
2 期
A research study to investigate the effects of CagriSema compared to placebo in people with type 2 diabetes and painful diabetic peripheral neuropathyType 2 diabetes and painful diabetic peripheral neuropathy2023-509662-38-00Novo Nordisk A/S53
招募中
1 期
A study to see the effect of NNC0194-0499 alone or in combination with semaglutide on blood sugar control in people living with type 1 diabetes.2024-519533-38-00Novo Nordisk A/S96
招募中
1 期
Investigating how CagriSema, semaglutide and cagrilintide regulate insulin effects in the body of people with type 2 diabetes.2023-509483-20-00Novo Nordisk A/S150
进行中（未招募）
不适用
Effects of NNC0194-0499, cagrilintide, and semaglutide alone or in combinations on liver damage and alcohol use in people with alcohol-related liver diseasejRCT2011240020Novo Nordisk Pharma Ltd.24