Obicetrapib + Repatha for Dyslipidemia

(VINCENT Trial)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: NewAmsterdam Pharma

Disqualifiers: High HbA1c, Recent CV events

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The goal of this open label 16 week trial is to evaluate Lp(a) levels for patients with elevated Lp(a) being treated with obicetrapib and obiceptrapib/evolocumab Patients will: Have baseline Lp(a) tested at randomization Take 10mg/dL obiceptrapib daily for 8 weeks and have Lp(a) tested at Week 8 Take 10 mg/dL obicetrapib daily/evolocumab 140 every other week for 8 weeks and have Lp(a) retested at Week 16

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

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 Obicetrapib for dyslipidemia?

Research shows that Obicetrapib, when used with high-intensity statins, significantly lowers bad cholesterol (LDL-C) and increases good cholesterol (HDL-C) in patients with dyslipidemia, making it a promising option for those at high risk of heart disease. ^{1 2 3 4 5}

Is the combination of Obicetrapib and Repatha safe for treating dyslipidemia?

Obicetrapib, when tested in combination with high-intensity statins, showed an acceptable safety profile in patients with dyslipidemia, suggesting it is generally safe for human use. ^{1 2 3 4 6}

How does the drug Obicetrapib + Repatha differ from other dyslipidemia treatments?

Obicetrapib + Repatha is unique because it combines a cholesterol-ester transfer protein inhibitor (Obicetrapib) with a PCSK9 inhibitor (Repatha), potentially offering a novel approach to lowering LDL cholesterol and increasing HDL cholesterol, which is different from traditional statin-based therapies. ^{2 5 7 8 9}

Research Team

Eligibility Criteria

This trial is for individuals with dyslipidemia, specifically those with triglycerides under 400 mg/dL, Lp(a) over 50 mg/dL, and LDL cholesterol above 70 mg/dL. It's not suitable for people who don't meet these blood lipid criteria.

Inclusion Criteria

Lp(a) greater than 50 mg/dL

LDL-C greater than 70 mg/dL

TG less than 400 mg/dL

Exclusion Criteria

I have not had a heart attack or stroke in the last 3 months.

HbA1c greater than or equal to 10 or FPG greater than or equal to 270 mg/dL

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants take 10mg/dL obicetrapib daily for 8 weeks and have Lp(a) tested at Week 8

8 weeks

1 visit (in-person) at Week 8

Treatment Phase 2

Participants take 10 mg/dL obicetrapib daily and evolocumab 140 mg/dL every other week for 8 weeks and have Lp(a) retested at Week 16

8 weeks

1 visit (in-person) at Week 16

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Obicetrapib (Other)

Trial Overview The study tests the effects of obicetrapib alone and combined with evolocumab on lowering Lp(a) levels in patients. Participants will take obicetrapib daily for eight weeks, then add evolocumab injections every two weeks for another eight weeks.

Participant Groups

Group I: obicetrapib/evolocumab combination Experimental Treatment 1 Intervention

obicetrapib 10 mg/dL daily for 8 weeks followed by obicetrapib 10 mg/dL daily + evolocumab 140 mg/dL every other week for 8 weeks

Who Is Running the Clinical Trial?

NewAmsterdam Pharma

Lead Sponsor

Trials

17

Recruited

13,900+

Findings from Research

In a randomized, double-blind, placebo-controlled trial involving 120 dyslipidaemic patients, the CETP inhibitor obicetrapib significantly reduced LDL cholesterol levels by up to 51% over 8 weeks when added to high-intensity statin therapy.

Obicetrapib also decreased apolipoprotein B and non-HDL cholesterol levels while increasing HDL cholesterol by up to 165%, demonstrating its potential as an effective treatment for high-cardiovascular-risk patients with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: a randomized phase 2 trial. Nicholls, SJ., Ditmarsch, M., Kastelein, JJ., et al.[2022]

Emerging drugs for dyslipidemia, such as lomitapide and inclisiran, are developed based on human genetic evidence, particularly focusing on lowering LDL cholesterol and triglycerides.

Several new therapies, including evinacumab and IONIS-ANGPTL3-LRx, target both LDL cholesterol and triglycerides, highlighting a multi-faceted approach to managing dyslipidemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid-Lowering Agents. Hegele, RA., Tsimikas, S.[2019]

In a study of 850 patients with familial hypercholesterolemia, adding torcetrapib to atorvastatin significantly increased HDL cholesterol levels but did not improve the progression of atherosclerosis, as measured by carotid intima-media thickness.

The combination therapy actually led to a worsening in the common carotid artery's thickness, indicating that despite lowering LDL cholesterol and raising HDL cholesterol, torcetrapib did not provide the expected cardiovascular benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. Kastelein, JJ., van Leuven, SI., Burgess, L., et al.[2020]

In a phase 2 trial with 97 patients, the combination of obicetrapib and ezetimibe significantly reduced LDL cholesterol levels by 63.4% compared to only 6.35% in the placebo group, demonstrating strong lipid-altering efficacy.

Obicetrapib was well tolerated with no safety issues reported, indicating that it is a safe adjunct therapy when added to high-intensity statin treatment for patients with elevated LDL cholesterol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obicetrapib plus ezetimibe as an adjunct to high-intensity statin therapy: A randomized phase 2 trial. Ballantyne, CM., Ditmarsch, M., Kastelein, JJ., et al.[2023]

Patients with combined dyslipidemia are at high risk for coronary artery disease and often need combination drug therapy to meet lipid level goals set by the US National Cholesterol Education Program.

While statin therapy is beneficial, combining statins with niacin or fibrates can increase the risk of muscle-related side effects, necessitating careful monitoring and consideration of the risks versus benefits for each patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy for combined dyslipidemia. Xydakis, AM., Ballantyne, CM.[2019]

Despite the availability of new lipid-lowering medications approved in the last decade, many patients still do not reach their cholesterol goals due to issues like statin intolerance and under-prescription of these new drugs.

The review suggests a practical stepwise approach for clinicians to effectively prescribe these novel medications, aiming to shift treatment strategies from relying solely on high-intensity statins to using combination therapies for high-risk patients to better prevent atherosclerotic cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A stepwise approach to prescribing novel lipid-lowering medications. Kakavand, H., Aghakouchakzadeh, M., Shahi, A., et al.[2022]

Statin therapy is essential for lowering LDL cholesterol and preventing atherosclerosis, but lifestyle changes are also crucial for managing hypertriglyceridemia and combined dyslipidemia.

If statins alone do not achieve cholesterol targets, combination therapies with medications like ezetimibe or fibrates should be considered, especially for patients with severe lipid abnormalities or progressing cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Update dyslipidemia]. Parhofer, KG.[2021]

Statins are effective in lowering LDL cholesterol levels and are considered the primary treatment for preventing metabolic disorders and cardiovascular disease, often used in combination with other medications like ezetimibe and bile acid sequestrants.

PCSK9 inhibitors have recently been approved for secondary prevention of cardiovascular disease and are being researched for their role in treating atherogenic dyslipidemia, highlighting the evolving landscape of LDL-C-lowering therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid-lowering therapy: Guidelines to precision medicine. Su, X., Cheng, Y., Chang, D.[2022]

Statins remain a cornerstone in treating high LDL-cholesterol levels, with new evidence supporting their use in broader patient groups and the introduction of more potent options like rosuvastatin and ezetimibe.

Emerging treatments for dyslipidemia, particularly in metabolic syndrome, include PPAR agonists like fibrates and glitazones, with promising combinations of statins and fibrates showing potential benefits for cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New strategies in the treatment of dyslipidemia: do we know how? Vrablík, M., Ceska, R.[2010]

References

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

Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: a randomized phase 2 trial. [2022]

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

Lipid-Lowering Agents. [2019]

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

Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. [2020]

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

Obicetrapib plus ezetimibe as an adjunct to high-intensity statin therapy: A randomized phase 2 trial. [2023]

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

Combination therapy for combined dyslipidemia. [2019]

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

A stepwise approach to prescribing novel lipid-lowering medications. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

[Update dyslipidemia]. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Lipid-lowering therapy: Guidelines to precision medicine. [2022]

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

New strategies in the treatment of dyslipidemia: do we know how? [2010]