NNC0194-0499 + Semaglutide for Fatty Liver Disease

No longer recruiting at 506 trial locations

Overseen By Novo Nordisk

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Novo Nordisk A/S

Must not be taking: Vitamin E, Pioglitazone, GLP-1 RAs

Disqualifiers: Chronic liver disease, HIV, HCV, others

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

Compensation: Varies

Number of Visits: 14

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether two medicines, NNC0194-0499 and semaglutide, can reduce liver damage in people with non-alcoholic steatohepatitis (NASH), a serious liver condition. NNC0194-0499 is a new liver-targeted treatment, while semaglutide is already used for type 2 diabetes and weight loss. Participants will receive injections of these medicines, another possible treatment option (NNC0174-0833, an experimental treatment), or a placebo (a dummy treatment). The trial is suitable for those with NASH confirmed by a recent liver biopsy and who experience liver-related issues in daily life. Participants will have regular clinic visits and phone calls with the study doctor over about 19 months. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

You may need to stop or adjust some medications before joining the trial. Specifically, treatments like vitamin E, pioglitazone, GLP-1 RAs, glucose-lowering agents, lipid-lowering medications, or weight loss medications must be stable for at least 90 days before the trial starts. It's best to discuss your current medications with the study doctor to see if any changes are needed.

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

Research has shown that semaglutide is generally safe for people with non-alcoholic fatty liver disease (NAFLD). One study found that it improves liver health and is safe to use. Semaglutide is already approved for treating type 2 diabetes and obesity, enhancing its safety reputation.

In contrast, NNC0194-0499 remains under study, so less information is available. Current research examines its safety and how it functions in the body, focusing on tolerance and potential side effects.

NNC0174-0833, another drug in the study, has undergone safety and tolerance checks. As a long-acting medication, it is being explored for its potential to treat liver conditions.

In summary, semaglutide is known to be safe, while NNC0194-0499 and NNC0174-0833 are newer and still undergoing testing. This research phase primarily focuses on ensuring their safety and identifying any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine NNC0194-0499 with semaglutide to tackle fatty liver disease in a novel way. Unlike current treatments, which often focus on lifestyle changes or medications like vitamin E and pioglitazone, this combination targets the condition by potentially reducing inflammation and fat accumulation in the liver. NNC0194-0499 is a new compound that, alongside semaglutide—a medication already known for treating diabetes and aiding weight loss—may offer a more effective approach. The weekly subcutaneous injections might also improve patient compliance compared to daily oral medications. This innovative combination has the potential to provide a more comprehensive treatment for fatty liver disease, addressing both metabolic and inflammatory aspects of the condition.

What evidence suggests that this trial's treatments could be effective for non alcoholic steatohepatitis?

Research has shown that semaglutide, one of the treatments in this trial, can help treat non-alcoholic fatty liver disease (NAFLD). In one study, 63% of participants taking semaglutide experienced reduced liver inflammation without worsening scarring. Another study found that it improved liver function and reduced liver stiffness. NNC0194-0499, another treatment option in this trial, is a new medicine being tested that targets the liver. When combined with semaglutide, it might more effectively reduce liver damage in people with non-alcoholic steatohepatitis (NASH). Additionally, NNC0174-0833, also under study in this trial, is being investigated for its potential to aid weight loss, which can also improve liver health. ^{1 2 3 5 6}

Who Is on the Research Team?

Clinical Transparency (dept. 1452)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

Adults with a certain liver condition called NASH and evidence of liver scarring (fibrosis stages 2-4) can join this study. They must have had a recent biopsy confirming the disease. Pregnant women or those planning pregnancy, heavy drinkers, and people on unstable doses of certain medications are excluded.

Inclusion Criteria

My liver biopsy confirms I have NASH.

My liver disease score is high enough to meet the trial's requirements.

I am of legal age in my country to consent to participate in a clinical trial.

Exclusion Criteria

I have had serious liver problems or a liver transplant.

I haven't taken GLP-1 receptor agonists in the last 90 days.

My diabetes, cholesterol, or weight loss medication doses have been stable for the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly injections of either two active drugs, one active drug and one placebo, or two placebo injections for 52 weeks

52 weeks

14 clinic visits, 9 phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NNC0174 0833 10 mg/mL
• NNC0174 0833 placebo
• NNC0194 0499 50 mg/mL
• Placebo (NNC0194-0499)
• Semaglutide
• Semaglutide placebo

Trial Overview

The trial is testing if two drugs, NNC0194-0499 and semaglutide, can help reduce liver damage in NASH patients when used together or separately compared to placebo injections. Participants will receive weekly injections for about 19 months with regular clinic visits and calls.

How Is the Trial Designed?

Group I: NNC0194-0499 7.5 mg + semaglutide 2.4 mg Experimental Treatment 2 Interventions

Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

Group II: NNC0194-0499 30 mg + semaglutide placebo 2.4 mg Experimental Treatment 2 Interventions

Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

Group III: NNC0194-0499 30 mg + semaglutide 2.4 mg Experimental Treatment 1 Intervention

Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

Group IV: NNC0194-0499 15 mg + semaglutide 2.4 mg Experimental Treatment 2 Interventions

Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

Group V: NNC0174-0833 2.4 mg + semaglutide 2.4 mg Experimental Treatment 2 Interventions

Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

Group VI: Placebo (NNC0194-0499) 30 mg + semaglutide 2.4 mg Active Control 2 Interventions

Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

Group VII: Placebo (NNC0194-0499) 7.5 mg + semaglutide placebo 2.4 mg Placebo Group 2 Interventions

Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

Group VIII: Placebo (NNC0194-0499) 15 mg + semaglutide placebo 2.4 mg Placebo Group 2 Interventions

Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

Group IX: Placebo (NNC0194-0499) 30 mg + semaglutide placebo 2.4 mg Placebo Group 2 Interventions

Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

Group X: Placebo (NNC0174-0833) 2.4 mg + semaglutide placebo 2.4 mg Placebo Group 2 Interventions

Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

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

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03856047

NCT03856047 | Research Study Investigating How Well ...

This study will look at the change in body weight in people taking NNC0174-0833, liraglutide and "dummy" medicine, from the start to the end of the study.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9884828/

Advancements in the treatment of non-alcoholic fatty liver ...

This review article has comprehensively discussed the research advancements in NAFLD treatment in recent years.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05016882

NCT05016882 | Research Study on Whether a ...

This study is being done to see if a combination of 2 medicines (called NNC0194-0499 and semaglutide) can reduce liver damage in patients with non alcoholic ...

4.

clinicaltrialsregister.eu

clinicaltrialsregister.eu/ctr-search/trial/2020-003566-39/IT

Clinical Trials Register

The European Union Clinical Trials Register allows you to search for protocol and results information on EU/EEA interventional clinical trials.

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S014067362100845X

Articles Safety, tolerability, pharmacokinetics, and ...

Cagrilintide (recommended international non-proprietary name for NNC0174-0833)17 is a long-acting acylated amylin analogue with agonistic effects on both native ...

6.

go.drugbank.com

go.drugbank.com/drugs/DB13928/clinical_trials?conditions=DBCOND0119264&phase=2&purpose=treatment&status=completed

Semaglutide Completed Phase 2 Trials for Metabolic ...

Research Study on Whether a Combination of 2 Medicines (NNC0194 0499 and Semaglutide) Works in People With Non-alcoholic Steatohepatitis (NASH).