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

Recruiting at 105 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

270 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Cagrilintide, CagriSema, NN-9388, Semaglutide/Cagrilintide, NNC0194-0499, Semaglutide, Ozempic, Wegovy, Rybelsus for treating alcoholic liver disease?

Research shows that semaglutide, a component of the drug, has been effective in improving liver conditions related to non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, and it has also shown promise in reducing alcohol use disorder symptoms in some patients. ^{1 2 3 4 5}

How is the drug Cagrilintide and Semaglutide unique for treating alcoholic liver disease?

Cagrilintide and Semaglutide, used together, are unique because they combine two drugs that have shown promise in treating liver conditions like non-alcoholic steatohepatitis (NASH) by reducing liver fat and inflammation. This combination could offer a novel approach for alcoholic liver disease, a condition with limited treatment options. ^{1 3 4 5 6}

What is the purpose of this trial?

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.

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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 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]

References

1. Netherlands 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series. [2023]

3. Spain pubmed.ncbi.nlm.nih.gov

Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity. [2023]

4. Netherlands 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. [2023]

5. United States 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. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-/-.Leiden Mice. [2023]