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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(NN9500-7730)

Effects of NNC0194-0499, cagrilintide, and semaglutide alone or in combinations on liver damage and alcohol use in people with alcohol-related liver disease

Kazunori Kinoshita

Novo Nordisk Pharma Ltd.

2-1-1, Marunouchi, Chiyodaku, Tokyo

jphc_clinical_trials@novonordisk.com

Kazunori Kinoshita

Novo Nordisk Pharma Ltd.

2-1-1, Marunouchi, Chiyodaku, Tokyo

+81-362661000

jphc_clinical_trials@novonordisk.com

Not Recruiting

June. 28, 2024

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. 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.
2. Age 18 years or above, and at the legal drinking age according to local requirements at the time of signing the informed consent.
3. 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.
4. ELF >=9.8 units.

1. Known or suspected hypersensitivity to study intervention(s) or related products.
2. 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 >= 25 kPa), a single rescreening is possible at the investigators discretion.
3. Documented causes of chronic liver disease other than Alcohol-related liver disease (ALD).
4. Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V1) or any known presence of HCV RNA or HBsAg within 2 years of screening (V1).
5. Presence or history of ascites more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or liver transplantation at screening (V1).
6. Alcohol hepatitis at randomisation (as defined by NIAAA).
7. Vibration Controlled Transient Elastography LSM >= 25 kPa at V2. If participants meet this criterion, rescreening is allowed once.
8. Presence or history of gastro-oesophageal varices >= grade 2 at V2. For participants with LSM >= 20 kPa as well as blood platelets count < 150,000 per uL of blood an oesophagogastroduodenoscopy performed no more than 52 weeks prior to V2 must be available at V2. Grade 2: varices projecting by one-third of the luminal diameter that cannot be compressed with air insufflation4.
9. BMI <= 25 kg/m2
10. 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.

Both

lcohol-related liver disease

Approximately 240 participants are to be enrolled and randomised into 7 treatment arms. For drug formulation reasons, three different pen-injectors will be used. Consequently, the participants will follow a 2:2:2:1:2:2:1 randomisation scheme into group A and group B, leading to two placebo arms (one placebo arm for each of group A and group B). The participants will be blinded to active versus placebo treatment, but they will be unblinded as to whether they are in group A or group B.
Group A will receive two s.c. injections once weekly, consisting of (a) two active drugs or (b) one active drug and one placebo or (c) two placebos. Group B will receive one s.c. injection once weekly, consisting of (a) two active drugs or (b) one active drug and one placebo or (c) two placebos. The study is double-blind within each of the two placebo-matched groups but unblinded between the 2 groups (groups A and B) .

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.
Primary endopoint
Change in Enhanced Liver Fibrosis (ELF) From baseline (week 0) to week 28
The primary clinical question of interest is: What is the difference between means in the compositea change in ELF score from baseline to week 28 in patients with alcohol-related liver disease, treated with each of the active treatments versus placebo, irrespective of adherence to investigational medicinal product and with use of ancillary therapy.

+81-11-831-5151

May. 09, 2024

No

Australia/Bulgaria/Canada/Czech Republic/Denmark/France/Germany/Greece/Italy/Netherlands/Poland/Spain/United States