NST-1024 for High Triglycerides

No longer recruiting at 30 trial locations

Overseen By Brandy Dupee

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NorthSea Therapeutics B.V.

Must be taking: Statins, Omega-3

Must not be taking: QT prolonging drugs

Disqualifiers: Type 1 diabetes, Stroke, Pancreatitis, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NST-1024 to lower high triglyceride levels, which are fats in the blood that can lead to heart problems. The study compares the effects of NST-1024 against a placebo (a pill with no active medication) to evaluate its effectiveness when combined with a healthy diet. It targets individuals with triglyceride levels between 500 and 2000 mg/dL who are already managing this condition with a stable treatment plan and lifestyle. Those with consistently high triglyceride levels who can maintain their current diet and exercise routine might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires that if you are on medications like statins, non-statin lipid-altering therapies, or weight loss drugs, your dosage must be stable for a certain period before and during the study. It doesn't specify stopping other medications, but you should discuss your specific situation with the study team.

Is there any evidence suggesting that NST-1024 is likely to be safe for humans?

Research has shown that NST-1024 was safe in earlier studies. In one study involving both healthy individuals and those with high triglycerides, NST-1024 was well-tolerated, with few reports of serious side effects. Researchers administered the treatment under controlled conditions and closely monitored participants.

Another study found that NST-1024 did not cause major health problems. Participants did not experience severe unexpected reactions, indicating that the treatment is generally safe for humans.

The drug underwent testing before the current trial, so its safety has been reviewed previously. Researchers continue to monitor for any issues during the trials to ensure participant safety. Overall, previous evidence suggests that NST-1024 is a safe option for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for high triglycerides, such as statins and fibrates, NST-1024 is unique because it is being studied for its ability to target triglycerides directly. Researchers are excited about NST-1024 because it is designed to be taken twice daily (BID) at a specific dosage of 400 mg, which may offer a more consistent control of triglyceride levels. Additionally, this drug could potentially provide a new mechanism of action compared to existing options, making it a promising candidate for those who do not respond well to current treatments.

What evidence suggests that NST-1024 might be an effective treatment for high triglycerides?

Research shows that NST-1024, also known as SEFA-1024, targets the connection between the gut and liver to help control high triglyceride levels in the blood. In animal studies, SEFA-1024 reversed weight gain and reduced liver fat, suggesting it could effectively lower triglycerides in people. Previous studies on similar treatments have had limited success, making NST-1024 a potentially better option. Early human trials confirmed its safety and mechanism of action. Participants in this trial will receive either NST-1024 or a placebo to evaluate its effectiveness in managing high triglycerides. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-79 with very high triglyceride levels (≥500 mg/dL and ≤2000 mg/dL). Participants must understand the study, follow its schedule, and give written consent. Women can join if they're not pregnant or breastfeeding, have had a hysterectomy or tubal ligation, are post-menopausal, or use effective contraception. Men's partners must also use effective birth control.

Inclusion Criteria

You understand the study procedures, agree to follow the study schedules, and are willing to give written consent before the screening assessments.

I have had a complete hysterectomy, tubal ligation, or I am post-menopausal.

I can take medication by mouth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Includes a TG qualifying period

Treatment

Participants receive NST-1024 400 mg BID or placebo for 28 days in a double-blind, randomized, parallel group, placebo-controlled setting

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• NST-1024
• Placebo

Trial Overview

The trial tests NST-1024 against a placebo in reducing triglycerides as an addition to diet changes over 28 days. It's a Phase IIa study with about 50 participants across multiple U.S. centers who will be randomly assigned to either the drug or placebo group in a double-blind setup (neither doctors nor patients know who gets what).

How Is the Trial Designed?

Group I: NST-1024 Active Control 1 Intervention

NST-1024 400 mg BID

Group II: Matched Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

NorthSea Therapeutics B.V.

Lead Sponsor

Trials

7

Recruited

590+

Published Research Related to This Trial

Lower doses of statins and bile acid sequestrants can effectively reduce LDL cholesterol levels, indicating that higher doses may not be necessary for optimal results.

Combining statins with bile acid sequestrants or niacin can provide an additive effect in lowering LDL cholesterol, suggesting a treatment strategy that maximizes efficacy while potentially reducing side effects and costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response characteristics of cholesterol-lowering drug therapies: implications for treatment. Schectman, G., Hiatt, J.[2019]

A 6-week treatment with lipid-lowering drugs results in consistent post-treatment cholesterol and triglyceride levels, suggesting that measuring absolute values after treatment is more reliable than looking at percentage reductions.

Combining clofibrate with Bufor leads to lower cholesterol levels compared to using either drug alone, while the effects of cholestyramine drugs like Cuemid and Questran cannot be accurately predicted based on previous clofibrate treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential drug therapy of the hyperlipoproteinaemias. The efficacy of lipid lowering drugs alone and in combination. Hansen, PF.[2013]

Gemfibrozil, at a daily dose of 1200 mg, effectively reduces total serum cholesterol, triglycerides, and apo B levels while increasing HDL cholesterol in patients with hyperlipidemia, demonstrating its efficacy as a lipid-lowering agent.

Long-term studies indicate that gemfibrozil has a more significant impact on lowering triglycerides than cholesterol, has few side effects, and maintains its effectiveness over time, making it a promising option for managing lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperlipoproteinemia, atherosclerosis and gemfibrozil. Nash, DT.[2017]

In a 3-month study involving 24 individuals with high triglycerides, gemfibrozil significantly reduced fasting plasma triglyceride levels from 4.01 to 1.34 mmol/L and increased HDL cholesterol from 0.54 to 0.67 mmol/L, indicating its efficacy in improving lipid profiles.

Despite these improvements in triglycerides and cholesterol, gemfibrozil did not affect plasma glucose or insulin responses to meals, suggesting that while it helps with lipid levels, it does not enhance insulin sensitivity or glucose disposal in patients with hypertriglyceridemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemfibrozil treatment of endogenous hypertriglyceridemia: effect on insulin-mediated glucose disposal and plasma insulin concentrations. Jeng, CY., Sheu, WH., Fuh, MM., et al.[2013]

New triglyceride-lowering therapies, including selective PPARα modulators and omega-3 fatty acid formulations, show promise for patients with severe hypertriglyceridemia (HTG) and those at high cardiovascular risk, particularly those with diabetes.

The phase 3 trial REDUCE-IT demonstrated the efficacy of high-dose icosapent ethyl, suggesting that these therapies can be beneficial for patients who are already on statin therapy but still have elevated triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational drugs in development for hypertriglyceridemia: a coming-of-age story. Rhainds, D., Brodeur, MR., Tardif, JC.[2020]

Clinical trials indicate that taking four 1-g capsules of prescription omega-3 ethyl ester fatty acids daily can significantly lower triglyceride levels in patients with very high triglycerides.

The treatment is well tolerated, suggesting it is a safe option for managing high triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating hypertriglyceridemia with prescription omega-3 fatty acid ethyl esters. Mickleborough, TD.[2010]

Type 2 diabetic patients on statins who had high triglycerides and low HDL cholesterol saw a 31% reduction in cardiovascular events when fenofibrate was added to their treatment.

This means that for every 20 patients treated with fenofibrate over five years, one cardiovascular event could be prevented, highlighting its efficacy in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACCORD LIPID study results strengthen guideline approach of adding fenofibrate to therapy of dyslipidaemic type 2 diabetic patients. Aalbers, J.[2013]

Diet and drug therapy are essential for managing LDL cholesterol levels, with dietary changes focusing on reducing saturated fats and cholesterol, but may not be sufficient alone for high-risk individuals.

Statins are the preferred medication for lowering LDL cholesterol and improving HDL cholesterol in patients with coronary artery disease, while other drugs like bile acid resins and niacin can be used to enhance treatment effects or target specific lipid abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid management: current diet and drug treatment options. Stone, NJ.[2019]

In a study of 20 hypertriglyceridemic men, micronized fenofibrate significantly reduced fasting triglyceride levels by 36% and triglyceride-rich lipoprotein levels by approximately 40%, indicating its efficacy in improving lipid profiles.

Fenofibrate also led to a 10% increase in HDL cholesterol and a 15% decrease in total cholesterol/HDL cholesterol ratios, suggesting a favorable shift towards healthier lipid levels, while it did not significantly affect LDL cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of micronized fenofibrate on plasma lipoprotein levels and hemostatic parameters of hypertriglyceridemic patients with low levels of high-density lipoprotein cholesterol in the fed and fasted state. Genest, J., Nguyen, NH., Theroux, P., et al.[2019]

Citations

1.

northseatherapeutics.com

northseatherapeutics.com/en/programs/sefa_1024/

SEFA-1024

SEFA-1024 is an oral, gut/liver targeted, semi-synthetic eicosapentaenoic acid (EPA) derivative in development for the treatment of severe hypertriglyceridemia ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9463121/

Structurally-engineered fatty acid 1024 (SEFA ...

In a long-term model of diet-induced obesity, SEFA-1024 reversed excessive weight gain, hepatic steatosis, elevated liver enzymes, hepatic ...

3.

ysioscapital.com

ysioscapital.com/2023/01/05/northsea-therapeutics-provides-clinical-update/

NorthSea Therapeutics provides clinical update

SEFA-1024 is an oral, highly lipophilic SEFA for the treatment of severe hypertriglyceridemia that is designed to target the gut-liver axis and ...

4.

synapse.patsnap.com

synapse.patsnap.com/drug/da20051d4a89439f91241ea5ce4b88cf

NST-1024 - Drug Targets, Indications, Patents

NST has concluded a Phase 1 clinical trial with single and multiple ascending doses and a drug-to-drug interaction study of SEFA-1024 in healthy volunteers with ...

5.

barchart.com

barchart.com/story/news/35870086/hypertriglyceridemia-clinical-landscape-companies-therapeutic-assessment-treatment-algorithm-and-pipeline-insights-key-players-northsea-therapeutics-arrowhead-pharmaceuticals-zhejiang-doer-b

Hypertriglyceridemia: Clinical Landscape, Companies ...

Existing treatment options often have limited effectiveness in reducing triglycerides (TG) and non-HDL cholesterol or improving glycemic control ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04630366

A Phase 1, First Time in Humans Study of NST-1024

... NST-1024 in Healthy Subjects and Otherwise Healthy Subjects with Elevated Triglycerides. This will be a double-blind, randomised, placebo-controlled, single ...

7.

hra.nhs.uk

hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/first-in-man-study-to-evaluate-nst-1024-in-volunteers/

First in Man Study to Evaluate NST-1024 in Volunteers

This study is a first-in-human study to evaluate the safety, tolerability, and pharmacokinetics (how the drug is used by the body) (PK) of NST-1024.