NNC0491-6075 for High Cholesterol

No longer recruiting at 1 trial location

Overseen By Novo Nordisk

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Novo Nordisk A/S

Must be taking: Statins

Must not be taking: Prescription medications

Disqualifiers: Hypersensitivity, Safety disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, NNC0491-6075, to determine its safety and effectiveness for people with high cholesterol. Participants will receive either the new medicine or a placebo, similar to a sugar pill. The trial consists of three parts: one for healthy individuals, one for people with high cholesterol, and one for healthy Japanese participants. Individuals with high cholesterol who are otherwise healthy might be suitable for the trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, providing participants the opportunity to be among the first to receive this new medicine.

Do I have to stop taking my current medications for this trial?

Yes, you generally need to stop taking prescription or non-prescription medications 14 days before screening, except for topical medications, occasional use of acetaminophen or NSAIDs, and stable statin therapy in Part B.

Will I have to stop taking my current medications?

The trial requires that you stop taking most prescription or non-prescription medications 14 days before screening, except for topical medications, occasional use of acetaminophen or NSAIDs for mild pain, and stable statin therapy in Part B.

Is there any evidence suggesting that NNC0491-6075 is likely to be safe for humans?

Research shows that specific safety information for NNC0491-6075 is not yet available. This treatment remains in the early testing stages, where researchers primarily assess its safety and how the body processes it.

Since NNC0491-6075 is undergoing its first human trials, information on possible side effects is limited. It has not been approved for any condition, so its effects on people are still under study. This phase ensures the treatment does not cause significant harm and is generally well-tolerated by participants. Joining such a study allows participants to help gather this crucial safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for high cholesterol?

NNC0491-6075 is unique because it offers a fresh approach to treating high cholesterol, potentially setting it apart from standard treatments like statins or PCSK9 inhibitors. This investigational drug features a novel mechanism of action and is being tested in both subcutaneous and intravenous forms, which could provide more flexibility in how it’s administered. Researchers are particularly excited about its potential for more targeted action and possibly fewer side effects, which could make it a game-changer for patients struggling with dyslipidemia.

What evidence suggests that NNC0491-6075 might be an effective treatment for high cholesterol?

Research has shown that NNC0491-6075 targets a protein called ANGPTL3, which helps control fat levels in the blood. This protein plays a crucial role in how the body processes fats. By blocking ANGPTL3, NNC0491-6075 might reduce unhealthy fats and cholesterol in the blood. Although limited data exists on its effectiveness in humans, studies suggest that targeting ANGPTL3 could help manage abnormal cholesterol levels. This trial will investigate NNC0491-6075 as a potential new method to lower cholesterol and improve heart health. ^{1 3 4 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 healthy adults aged 18-55, or those with high fat levels in the blood aged 18-64. Participants must have a BMI of 18.5 to 34.9 kg/m^2 and stable health as confirmed by medical exams. Those on statins must be on a steady dose for at least 8 weeks prior.

Inclusion Criteria

I am 18-55 years old, healthy, with a BMI of 18.5-34.9, and of Japanese descent.

I am 18-64, healthy with stable cholesterol treatment, and my BMI is between 18.5 and 34.9.

Exclusion Criteria

I do not have any health issues that could make this study unsafe for me.

Your blood test results for liver and muscle function are not within certain ranges.

Known or suspected hypersensitivity to study intervention(s) or related products

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A - Single Dose Administration

Participants receive a single dose of NNC0491-6075 or placebo, administered subcutaneously or intravenously

110 days

Part B - Multiple Dose Administration

Participants with dyslipidemia receive weekly doses of NNC0491-6075 or placebo for four weeks

131 days

Part C - Single Dose Administration in Japanese Participants

Healthy Japanese participants receive a single dose of NNC0491-6075 or placebo, administered subcutaneously or intravenously

110 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NNC0491-6075

Trial Overview

The study tests NNC0491-6075's safety and how it works in the body compared to a placebo. It has three parts: single-dose effects in healthy people (Part A), weekly doses for four weeks in people with high fat levels (Part B), and single-dose effects in healthy Japanese participants (Part C).

How Is the Trial Designed?

Group I: Part C: Single ascending dose (SAD) cohorts in healthy Japanese participants: Experimental Treatment 2 Interventions

Healthy Japanese participants, randomized in the ratio 3:1 in each of the cohorts will receive single ascending dose of either NNC0491-6075 or placebo in 3 cohorts (Cohort C1,C2 and C3). The route of administration will be subcutaneous or intravenous.

Group II: Part B Multiple ascending dose (MAD) cohorts in dyslipidemia participants Experimental Treatment 2 Interventions

Participants with dyslipidemia, randomized in the ratio 2:1 in each of the cohorts will receive multiple ascending dose of either NNC0491-6075 or placebo in 3 cohorts (Cohort B1,B2 and B3). Participants will receive subcutaneous injections of either NNC0491-6075 or placebo once weekly for 4 weeks.

Group III: Part A Single ascending dose (SAD) cohorts in healthy participants: Experimental Treatment 2 Interventions

Healthy participants, randomized in 3:1 ratio in each of the cohorts will receive single ascending dose of either NNC0491-6075 or placebo in 5 cohorts (Cohort A1, A2, A3, A4 and A5). In cohorts A1, A2 and A3, the participants will receive subcutaneous injection, whereas in cohorts A4 and A5 the administration will be performed intravenously.

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

Statins, such as atorvastatin and simvastatin, are highly effective in lowering cholesterol levels by inhibiting cholesterol synthesis in the liver, which helps reduce the risk of coronary heart disease (CHD).

The article reviews the pharmacological data of both established and novel statins, highlighting that differences in their pharmacokinetics may contribute to varying levels of toxicity and adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), including rosuvastatin and pitavastatin. Igel, M., Sudhop, T., von Bergmann, K.[2022]

Non-HDL cholesterol (c-NO-HDL) is a better predictor of cardiovascular disease risk than low-density lipoprotein cholesterol (c-LDL), as it accounts for a broader range of atherogenic lipoproteins.

Intervention studies show that lowering c-NO-HDL levels reduces the incidence of ischemic heart disease, leading to its recommendation as a therapeutic target in managing dyslipidemia, with specific target levels set for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-HDL cholesterol as a therapeutic goal. Brea, A., Hernández-Mijares, A., Millán, J., et al.[2020]

The National Cholesterol Education Program (NCEP) emphasizes the importance of regular cholesterol screenings for all adults at least every 5 years to manage cholesterol levels effectively.

For individuals with cholesterol levels above 5.2 mmol/L (200 mg/dl), dietary changes are recommended, and those with levels exceeding 6.2 mmol/L (240 mg/dl) may require more intensive treatment, including medication, but only after confirming LDL-cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The US National Cholesterol Education Program. Adult treatment guidelines. Hulley, SB.[2018]

Gastrointestinal symptoms were the most frequently reported adverse drug reactions (ADRs) for non-statin antihyperlipidaemic drugs, accounting for about 50% of cases, with cholestyramine and gemfibrozil being the primary culprits.

Niacin and acipimox were associated with a significant incidence of skin symptoms, while niacin and gemfibrozil were also linked to liver disease symptoms, highlighting the need for monitoring these side effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of non-statin antihyperlipidaemic drugs in China from 1989 to 2019: a national database analysis. Tsui, L., Chen, L., Ye, P., et al.[2023]

The National Cholesterol Education Program (NCEP) emphasizes dietary therapy as the primary treatment for high blood cholesterol, aiming to lower LDL-cholesterol levels through specific dietary modifications.

The Step-One Diet recommends limiting total fat to less than 30% of calories and saturated fat to less than 10%, with further restrictions in the Step-Two Diet if LDL-cholesterol goals are not met, highlighting the importance of diet in preventing coronary heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The National Cholesterol Education Program: implications for dietetic practitioners from the Adult Treatment Panel recommendations. Ernst, ND., Cleeman, J., Mullis, R., et al.[2013]

Non-high-density lipoprotein cholesterol (non-HDL-C) is a crucial measure for assessing the risk of coronary heart disease (CHD), especially in patients with triglycerides ≥200 mg/dL, and should be a primary target for therapy.

A study involving 21,448 participants over 11 years found that high non-HDL-C levels independently increased CHD risk, suggesting that non-HDL-C is a more effective marker than LDL-C for guiding cardiovascular prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of non-HDL cholesterol in risk stratification for coronary artery disease. Rana, JS., Boekholdt, SM., Kastelein, JJ., et al.[2021]

Statins have been proven effective in improving lipid levels and significantly reducing the risk of atherosclerotic coronary artery disease (CAD), which leads to lower morbidity and mortality rates associated with CAD.

While statins are generally well tolerated, there are safety concerns regarding potential adverse effects on muscles, liver, kidneys, and the nervous system, with some risks being well-documented and others remaining speculative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin safety: an overview and assessment of the data--2005. Bays, H.[2022]

In a study of 269 healthy prepubescent children, only 3.7% had high non-HDL cholesterol (NHDL-c) levels, while 17.1% had a family history of early cardiovascular disease (HCVD), indicating that high NHDL-c is relatively rare in this population.

The study found a weak association between family HCVD and NHDL-c levels, but identified insulin resistance and diastolic blood pressure as stronger independent factors linked to elevated NHDL-c, suggesting that these may be more critical risk factors for cardiovascular disease in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Family history of cardiovascular disease and non-HDL cholesterol in prepubescent non-obese children. Strufaldi, MW., Souza, FI., Puccini, RF., et al.[2022]

Statin therapy has been shown to significantly reduce the risk of ischemic cardiovascular events and may even lower mortality within the first year of treatment, based on evidence from landmark trials.

Patients with moderately elevated cholesterol levels can safely benefit from statin treatment, as it is well tolerated and can prevent serious clinical events related to coronary artery disease when aggressive therapy is applied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Best practice--ongoing polemics. Paoletti, R., Bellosta, S.[2019]

In patients with chronic kidney disease (CKD), lowering total and LDL cholesterol has not been shown to effectively reduce the risk of coronary heart disease (CHD), despite its established link to atherosclerosis in the general population.

Statins, while generally well-tolerated, can cause dose-related side effects such as muscle pain and liver enzyme elevations, particularly in elderly CKD patients, necessitating cautious dosing and monitoring when used alongside certain other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in chronic kidney disease, dialysis, and transplant patients. Olyaei, A., Greer, E., Delos Santos, R., et al.[2022]

In a study involving 1361 veterans, only 35.4% of patients on pravastatin for secondary prevention of coronary heart disease (CHD) met their LDL cholesterol goals, highlighting a significant gap in achieving recommended cholesterol levels.

After converting 1115 patients from pravastatin to simvastatin, the study aims to assess the effectiveness of this change in improving LDL cholesterol levels, as initial results indicate that less than half of the patients were meeting their cholesterol targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale, design, and baseline results of the Pravastatin-to-Simvastatin Conversion Lipid Optimization Program (PSCOP). Ito, MK., Stolley, SN., Morreale, AP., et al.[2019]

Statin therapy has significantly reduced coronary heart disease (CHD) morbidity and mortality, as shown in controlled clinical trials involving both primary and secondary prevention patients.

Beyond lowering cholesterol levels, statins also provide nonlipid benefits, including improved endothelial function and stabilization of arterial plaques, which contribute to their overall effectiveness in heart disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggressive lipid therapy in the statin era. Farmer, JA.[2019]

Statin and LDL-lowering treatments have been shown to effectively reduce coronary heart disease (CHD) and cardiovascular disease (CVD) events across various high-risk patient groups, as confirmed by multiple clinical trials.

Recent findings indicate that some patients may experience limited benefits from lipid-lowering treatments due to non-reversible cardiovascular risks, suggesting that treatment decisions should consider both absolute risk and the specific clinical context, in line with updated guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reversible and non-reversible cardiovascular risk in patients treated with lipid-lowering therapy: analysis of SEAS and JUPITER trials. Poli, A., Corsini, A.[2015]

In a study of 19,422 patients who started statin therapy, those who had follow-up lipid tests and physician visits were significantly more likely to adhere to their medication regimen, with adherence rates increasing by 45% for those receiving both types of care.

The findings suggest that regular physician follow-up and lipid testing after starting statin treatment can improve patient adherence, highlighting the importance of ongoing medical support in managing cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Follow-up lipid tests and physician visits are associated with improved adherence to statin therapy. Benner, JS., Tierce, JC., Ballantyne, CM., et al.[2018]

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