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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 270
- 试验地点
- 187
- 主要终点
- Change in Enhanced Liver Fibrosis (ELF)
研究概览
简要总结
The study will look at the effects of NNC0194-0499, cagrilintide and semaglutide, on liver damage and alcohol use in participants with alcoholic liver disease. Participants will get NNC0194-0499, semaglutide, cagrilintide or ''dummy" medicine in different treatment combinations. Which treatment participants get is decided by chance. The study will last for about 39 weeks.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Age 18 years or above, and at the legal drinking age according to local requirements at the time of signing the informed consent.
- •Patient-reported history of alcohol overuse for greater than or equal to 5 years with an alcohol history of a mean of greater than or equal to 50 grams (male)/40 grams (female) pr day for the last year leading up to the time of signing informed consent.
- •Enhanced Liver Fibrosis (ELF) greater than or equal to 9.0 units.
排除标准
- •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 7 is met (Vibration Controlled Transient Elastography liver stiffness measurement (LSM) is greater than or equal to 25 Kilopascal (kPa)), a single rescreening is possible at the investigator's discretion.
- •Documented causes of chronic liver disease other than Alcohol-related liver disease (ALD).
- •Positive hepatitis B surface antigen (HBsAg), positive human immunodeficiency virus-1 (HIV-1) or HIV-2 antibody (Ab), positive hepatitis C virus (HCV) ribonucleic acid (RNA) at screening (V1) or any known presence of HCV RNA or HBsAg within 2 years of screening visit 1 (V1).
- •Presence or history of ascites more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or liver transplantation at screening (V1).
- •Alcohol hepatitis at randomisation (as defined by National Institute on Alcohol Abuse and Alcoholism (NIAAA)).
- •Vibration Controlled Transient Elastography liver stiffness measurement (LSM) greater than or equal to 25 kPa at visit 2 (V2). If participants meet this criterion, rescreening is allowed once.
- •Presence or history of gastro-oesophageal varices greater than or equal to grade 2* at V
- •For participants with LSM greater than or equal to 20 kPa as well as blood platelets count less than 150,000 per microliter (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 insufflation
- •Body mass index (BMI) less than or equal to 25 Kilogram Per Square Meter (kg/m^2).
- •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-dependency.
研究组 & 干预措施
NNC0194-0499 + semaglutide
Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide.
干预措施: NNC0194-0499 (Drug)
NNC0194-0499 + semaglutide
Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide.
干预措施: Semaglutide (Drug)
NNC0194-0499 + semaglutide placebo
Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide placebo.
干预措施: NNC0194-0499 (Drug)
NNC0194-0499 + semaglutide placebo
Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide placebo.
干预措施: Semaglutide placebo (Group A) (Drug)
NNC0194-0499 placebo + semaglutide
Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide.
干预措施: Semaglutide (Drug)
NNC0194-0499 placebo + semaglutide
Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide.
干预措施: NNC0194-0499 placebo (Drug)
NNC0194-0499 placebo + semaglutide placebo
Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide placebo.
干预措施: NNC0194-0499 placebo (Drug)
NNC0194-0499 placebo + semaglutide placebo
Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide placebo.
干预措施: Semaglutide placebo (Group A) (Drug)
CagriSema
Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide.
干预措施: Cagrilintide + semaglutide (Drug)
Cagrilintide + semaglutide placebo
Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide placebo.
干预措施: Cagrilintide (Drug)
Cagrilintide + semaglutide placebo
Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide placebo.
干预措施: Semaglutide placebo (Group B) (Drug)
Cagrilintide placebo + semaglutide placebo
Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide placebo in combination with semaglutide placebo.
干预措施: Cagrilintide placebo (Drug)
Cagrilintide placebo + semaglutide placebo
Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide placebo in combination with semaglutide placebo.
干预措施: Semaglutide placebo (Group B) (Drug)
结局指标
主要结局
Change in Enhanced Liver Fibrosis (ELF)
时间窗: From week 0 to week 28
Measured as logarithm score
次要结局
- Change in Pro-peptide of Collagen 3 (Pro-C3)(From week 0 to week 28)
- Change in liver stiffness assessed by Vibration Controlled Transient Elastography (VCTE)(From week 0 to week 28)
- Change in liver steatosis assessed by Controlled Attenuated Parameter (CAP)(From week 0 to week 28)
- Change in Alanine Aminotransferase (ALT)(From week 0 to week 28)
- Change in Aspartate Aminotransferase (AST)(From week 0 to week 28)
- Number of treatment emergent adverse events(From week 0 to week 35)
- Change in Phosphatidylethanol (PEth)(From week -4 to week 28)
- Change in alcohol amount measured by timeline followback (TLFB)(From week -4 to week 28)
- Change in total cholesterol(From week 0 to week 28)