BridgeMD
Effects of NNC0194-0499, cagrilintide, and semaglutide alone or in combinations on liver damage and alcohol use in people with alcohol-related liver disease
EU CTIS ID: 2023-508170-28-00
What this study is testing
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.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Participants are eligible to be included in the study only if all the following criteria apply:
- 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. Male or female.
- 3. 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.
- 4. 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.
- 5. ELF ≥ 9.0 units.
You likely can't join if
- Liver-related exclusion criteria:
- 10. Treatment with GLP-1 RAs within 90 days prior to V1.
- 11. Presence of acute pancreatitis within 180 days prior to V1.
- 1.Documented causes of chronic liver disease other than Alcohol-related liver disease (ALD).
- 12. History or presence of type 1 diabetes at V1.
- 13.Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
See the full eligibility criteria
Who can join
- Participants are eligible to be included in the study only if all the following criteria apply:
- 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. Male or female.
- 3. 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.
- 4. 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.
- 5. ELF ≥ 9.0 units.
What rules you out
- Liver-related exclusion criteria:
- 10. Treatment with GLP-1 RAs within 90 days prior to V1.
- 11. Presence of acute pancreatitis within 180 days prior to V1.
- 1.Documented causes of chronic liver disease other than Alcohol-related liver disease (ALD).
- 12. History or presence of type 1 diabetes at V1.
- 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)
- 15. CIWA-Ar score ≥ 10
- Mental health related exclusion criteria:
- 16. 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 V1. AST > 5 x ULN at V1.
- 17. A history of a suicidal attempt within 5 years before screening
- 18. Suicidal ideation corresponding to type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at V2.
- 19. 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:
- 20. BMI ≤ 25 kg/m2.
- 21.Known or suspected hypersensitivity to study intervention(s) or related products. (incl. excipients).
- 22. 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 <9.8.
- 23. 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.
- 24. 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 V1. Total bilirubin level > 1.5 mg/dL is allowed if conjugated bilirubin is within normal range.
- 25. Presence or history of malignant neoplasms other than hepatocellular carcinoma within 5 years prior to V1. Basal and squamous cell skin cancer and any carcinoma in situ are allowed.
- 26. History or presence of chronic pancreatitis at V1.
- 27. Uncontrolled thyroid disease, as assessed by the investigator.
- 28. 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 V1.
- 3.Presence or history of ascites more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or liver transplantation at screening (V1).
- 29. Any participant for whom substantial weight loss might, in the investigator’s opinion, jeopardise the safety of the participant.
- 30. 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.
- 32. 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 V1.
- 4. Alcohol hepatitis at randomisation (as defined by NIAAA75)
- 5. Vibration Controlled Transient Elastography LSM ≥ 25 kPa at V2. If participants meet this criterion, rescreening is allowed once.
- 6. 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 µL 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
- 7.Presence or history of hepatocellular carcinoma at V1
- 8. 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 V1.
- e) MELD score > 12 points at V1.
- f) eGFR < 60 mL/min/1.73 m2 as defined according to the CKD-EPI creatinine equation (CKD-EPI, 2021) at V1. HbA1c > 80 mmol/mol (9.5%) at V1. Platelet count < 100,000 per µL of blood at V1.
- Diabetes-related exclusion criteria:
- 9. For participants with type 2 diabetes: Uncontrolled and potentially unstable diabetic retinopathy or maculopathy verified by a fundus examination performed within 90 days prior to V1 or in the period between V1 and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examinations.
The study team makes the final eligibility decision.
Where it's taking place
- Japan
- Canada
- Australia
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Japan; Canada; Australia; United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.