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

Recruiting in Palo Alto (17 mi)

+106 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Novo Nordisk A/S

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

Prior Safety Data

Trial Summary

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.

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.

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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.

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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

I am 18 or older and legally allowed to drink alcohol.

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)

Trial 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)

Participant Groups

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.

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

The Institute for Liver Health Chandler, AZ

Del Sol Research Management, LLC Tucson, AZ

The Liver Institute Dallas, TX

Arizona Liver Center Tucson, AZ

More Trial Locations

Who Is Running the Clinical Trial?

Novo Nordisk A/S Lead Sponsor

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] Patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis are at high risk of liver-related and all-cause morbidity and mortality. We investigated the efficacy and safety of the glucagon-like peptide-1 analogue semaglutide in patients with NASH and compensated cirrhosis.

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] Objective: Despite being a major cause of preventable death worldwide, alcohol use disorder (AUD) currently has only 3 FDA-approved pharmacotherapies. The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide has shown promise in preclinical studies for reducing alcohol consumption, but there are currently no randomized clinical trials that associate a decline in AUD symptoms with semaglutide use. This case series presents 6 patients with positive AUD screenings who were treated with semaglutide for weight loss. All subsequently exhibited significant improvement in AUD symptoms.

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

Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity. [2023] This work aims to assess the effect of weekly subcutaneous semaglutide on biomarkers of metabolic-associated fatty liver disease (MAFLD), namely the hepatic steatosis index (HSI) and the fibrosis-4 (FIB-4) index, at 24 weeks in outpatients attended to in internal medicine departments.

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] This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 24 weeks of semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).

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] Semaglutide, a peptidic GLP-1 receptor agonist, has been clinically approved for treatment of type 2 diabetes mellitus and is available in subcutaneous and oral dosage form. Diabetes, insulin resistance, and obesity are responsible for the pathological manifestations of non-alcoholic steatohepatitis (NASH). Similarly, insulin resistance in brain is also responsible for neurodegeneration and impaired cognitive functions.

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

Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-/-.Leiden Mice. [2023] Semaglutide, a glucagon-like peptide-1 receptor agonist, is an antidiabetic medication that has recently been approved for the treatment of obesity as well. Semaglutide is postulated to be a promising candidate for the treatment of non-alcoholic steatohepatitis (NASH). Here, Ldlr-/-.Leiden mice received a fast-food diet (FFD) for 25 weeks, followed by another 12 weeks on FFD with daily subcutaneous injections of semaglutide or vehicle (control). Plasma parameters were evaluated, livers and hearts were examined, and hepatic transcriptome analysis was performed. In the liver, semaglutide significantly reduced macrovesicular steatosis (-74%, p < 0.001) and inflammation (-73%, p < 0.001) and completely abolished microvesicular steatosis (-100%, p < 0.001). Histological and biochemical assessment of hepatic fibrosis showed no significant effects of semaglutide. However, digital pathology revealed significant improvements in the degree of collagen fiber reticulation (-12%, p < 0.001). Semaglutide did not affect atherosclerosis relative to controls. Additionally, we compared the transcriptome profile of FFD-fed Ldlr-/-.Leiden mice with a human gene set that differentiates human NASH patients with severe fibrosis from those with mild fibrosis. In FFD-fed Ldlr-/-.Leiden control mice, this gene set was upregulated as well, while semaglutide predominantly reversed this gene expression. Using a translational model with advanced NASH, we demonstrated that semaglutide is a promising candidate with particular potential for the treatment of hepatic steatosis and inflammation, while for the reversal of advanced fibrosis, combinations with other NASH agents may be necessary.