NNC0194-0499, Cagrilintide, and Semaglutide for Alcoholic Liver Disease

Not currently recruiting at 125 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novo Nordisk A/S

Disqualifiers: Chronic liver disease, Hepatitis B, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of three potential treatments—NNC0194-0499, cagrilintide, and semaglutide (a medication used for weight management and type 2 diabetes)—on liver damage and alcohol use in individuals with alcoholic liver disease. Participants will receive different combinations of these treatments or a placebo ("dummy" medicine). The goal is to determine which combination might reduce liver damage and alcohol consumption over 39 weeks. Individuals who have been drinking heavily for over five years and have liver issues related to alcohol use might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of NNC0194-0499 and semaglutide has been studied for its effects on liver conditions. Although specific safety information for this treatment remains limited, semaglutide is already FDA-approved for managing blood sugar in type 2 diabetes, suggesting it is generally well-tolerated.

For the combination of cagrilintide and semaglutide, known as CagriSema, studies have demonstrated that these drugs can be safely used together. Previous research linked this combination to improved blood sugar control, indicating a promising safety profile.

As this trial is in the middle phase, some safety data is available for these treatments, but more evidence is needed. Participants tolerated these drugs in earlier studies, but monitoring for side effects remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for alcoholic liver disease because they bring fresh mechanisms and combinations that differ from existing options. Unlike standard treatments that often focus on managing symptoms or slowing liver damage, Cagrilintide and NNC0194-0499 are being tested for their potential to address the underlying metabolic factors contributing to liver disease. Cagrilintide is a novel compound that works by mimicking a hormone in the body to regulate appetite and energy balance, while NNC0194-0499 is being explored for its ability to modulate metabolic pathways. Additionally, combining these with Semaglutide, a drug known for its effectiveness in metabolic conditions like diabetes, could offer a comprehensive approach to tackling alcoholic liver disease. This innovative angle has researchers hopeful for more effective treatments in the future.

What evidence suggests that this trial's treatments could be effective for alcoholic liver disease?

Research has shown that semaglutide, one of the treatments in this trial, may help with alcohol use disorder (AUD). In a small group of people with AUD who took semaglutide for weight loss, all participants experienced significant improvements in their alcohol use. This suggests semaglutide might also aid in addressing liver problems related to alcohol. NNC0194-0499, another treatment option in this trial, is under study to determine its potential to reduce liver damage in conditions not caused by alcohol, such as non-alcoholic steatohepatitis (NASH). Researchers hope it could also help with liver damage from alcohol. Cagrilintide, often used with semaglutide and included in this trial, is being evaluated for its effects on liver health, but specific results for alcoholic liver disease are still being gathered. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for individuals with alcoholic liver disease. Participants should be willing to receive injections of either the study medications or placebos and be available for the duration of the 39-week study. Specific inclusion and exclusion criteria details are not provided, but typically these would outline health conditions, lifestyle factors, or other medications that could affect participation.

Inclusion Criteria

Informed consent obtained before any study-related activities

Enhanced Liver Fibrosis (ELF) greater than or equal to 9.8 units

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) per day for the last year leading up to the time of signing informed consent

Exclusion Criteria

I have been diagnosed with alcohol hepatitis.

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

Body mass index (BMI) less than or equal to 25 Kilogram Per Square Meter (kg/m^2)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive NNC0194-0499, cagrilintide, semaglutide, or placebo in different combinations

28 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cagrilintide
• NNC0194-0499
• Semaglutide

Trial Overview The trial is testing how NNC0194-0499, cagrilintide, semaglutide alone or in combination can impact liver damage and alcohol use in people with alcoholic liver disease. Treatments are assigned randomly and include both active drugs and placebos (dummy medicine) to compare effects.

How Is the Trial Designed?

Group I: NNC0194-0499 placebo + semaglutide Experimental Treatment 2 Interventions

Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide.

Group II: NNC0194-0499 + semaglutide placebo Experimental Treatment 2 Interventions

Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide placebo.

Group III: NNC0194-0499 + semaglutide Experimental Treatment 2 Interventions

Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide.

Group IV: Cagrilintide + semaglutide placebo Experimental Treatment 2 Interventions

Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide placebo.

Group V: CagriSema Experimental Treatment 1 Intervention

Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide.

Group VI: Cagrilintide placebo + semaglutide placebo Placebo Group 2 Interventions

Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide placebo in combination with semaglutide placebo.

Group VII: NNC0194-0499 placebo + semaglutide placebo Placebo Group 2 Interventions

Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide placebo.

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

In a case series of 6 patients with alcohol use disorder (AUD) treated with semaglutide for weight loss, all patients showed significant improvement in AUD symptoms, with an average reduction of 9.5 points on the AUDIT scale (P < 0.001).

These findings suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide may be a promising new treatment option for AUD, although further randomized clinical trials are necessary to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series. Richards, JR., Dorand, MF., Royal, K., et al.[2023]

Semaglutide, a GLP-1 receptor agonist approved for type 2 diabetes and obesity, has shown significant weight reduction and hepatoprotective effects in non-alcoholic steatohepatitis (NASH) based on phase-3 clinical trials.

In addition to its benefits for obesity and diabetes, semaglutide demonstrates neuroprotective potential in neurodegenerative disorders like Parkinson's and Alzheimer's disease, suggesting it could be a promising treatment for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review. Mahapatra, MK., Karuppasamy, M., Sahoo, BM.[2022]

In a systematic review of 8 studies involving 2413 patients, 24 weeks of semaglutide treatment significantly reduced liver enzymes (alanine transaminase and aspartate transaminase) and improved liver fat content and stiffness, indicating its efficacy in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

Despite its benefits, semaglutide treatment was associated with a higher risk of serious gastrointestinal adverse events, such as nausea and vomiting, highlighting the need for careful monitoring of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Bandyopadhyay, S., Das, S., Samajdar, SS., et al.[2023]

In a study using Ldlr-/-.Leiden mice, semaglutide significantly reduced liver fat and inflammation by 74% and 73% respectively, indicating its potential effectiveness in treating non-alcoholic steatohepatitis (NASH).

While semaglutide improved liver health by reversing certain gene expressions associated with NASH, it did not significantly affect liver fibrosis, suggesting that it may need to be combined with other treatments for advanced fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-/-.Leiden Mice. Inia, JA., Stokman, G., Morrison, MC., et al.[2023]

In a phase 2 trial involving 71 patients with NASH-related cirrhosis, semaglutide did not significantly improve liver fibrosis or lead to NASH resolution compared to placebo after 48 weeks.

The safety profile of semaglutide was similar to that of the placebo, with no new safety concerns identified, and common side effects included nausea and diarrhea, but overall liver and kidney function remained stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Loomba, R., Abdelmalek, MF., Armstrong, MJ., et al.[2023]

In a study of 213 patients with type 2 diabetes, weekly subcutaneous semaglutide significantly reduced biomarkers of metabolic-associated fatty liver disease (MAFLD), specifically the hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) index, over 24 weeks.

The improvements in liver health were primarily linked to weight loss and reductions in triglyceride levels and insulin resistance, indicating that semaglutide's benefits extend beyond just controlling blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity. Carretero-Gómez, J., Carrasco-Sánchez, FJ., Fernández-Rodríguez, JM., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06409130

NCT06409130 | Effects of NNC0194-0499, Cagrilintide ... 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.

2. mayo.edu mayo.edu/research/clinical-trials/cls-20571137

Effects of NNC0194-0499, Cagrilintide, And Semaglutide ... The purpose of this study is to investigate fixed doses of NNC0194-0499, Cagrilintide, Semaglutide alone and NNC0194-0499 or Cagrilintide in combination with ...

3. withpower.com withpower.com/trial/phase-2-liver-diseases-4-2024-8894a?condition=cirrhosis&ageList=65&overallStatus=Recruiting&hasNoPlacebo=false

NNC0194-0499, Cagrilintide, and Semaglutide for ... In a case series of 6 patients with alcohol use disorder (AUD) treated with semaglutide for weight loss, all patients showed significant improvement in AUD ...

4. bu.trialstoday.org bu.trialstoday.org/trial/NCT06409130

Boston University - Clinical & Translational Science Institute 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.

5. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06409130/

Trial | NCT06409130 The study will look at the effects of NNC0194-0499, cagrilintide and semaglutide, on liver damage and alcohol use in participants with alcoholic liver ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673623011637

Articles Efficacy and safety of co-administered once-weekly ... We found that treatment with co-administered semaglutide 2·4 mg and cagrilintide 2·4 mg (CagriSema) resulted in clinically relevant improvements in glycaemic ...

7. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?id=22470&isClinicalTrial=True

ANZCTR - Registration ... Cagrilintide Alone and in Combination With Semaglutide on Liver Damage and Alcohol Use in People With Alcohol-related Liver Disease. Query ...