Obicetrapib + Repatha for Dyslipidemia

(VINCENT Trial)

Overseen By Ashley Walker

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NewAmsterdam Pharma

Disqualifiers: High HbA1c, Recent CV events

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

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

Compensation: Varies

Number of Visits: 2

69 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for people with dyslipidemia, characterized by abnormal levels of lipids (fats) in the blood. Researchers aim to determine how effectively obicetrapib, both alone and combined with evolocumab (a medication that lowers cholesterol), can reduce Lp(a) levels, a type of fat linked to heart problems. Participants will take obicetrapib for 8 weeks, followed by a combination of obicetrapib and evolocumab for another 8 weeks. Individuals with high Lp(a) levels and cholesterol, but not extremely high blood sugar, may be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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.

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

Research shows that obicetrapib, when combined with other cholesterol-lowering drugs, is generally well-tolerated. Most people experience only mild side effects, mainly related to the stomach. Studies are ongoing to fully understand its safety when combined with evolocumab. However, evolocumab is already approved for managing cholesterol and is usually well-tolerated, suggesting that the combination is likely safe. The current phase of the trial indicates that earlier research found the treatment safe enough for testing on more people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Obicetrapib is unique because it works differently from most current dyslipidemia treatments. While traditional options like statins primarily focus on reducing cholesterol by inhibiting its production in the liver, obicetrapib is a CETP inhibitor. This means it targets a protein that transfers cholesterol between lipoproteins, potentially leading to improved cholesterol balance in the blood. Researchers are excited because combining obicetrapib with evolocumab, a PCSK9 inhibitor, might offer a powerful duo that enhances cholesterol-lowering effects beyond what existing treatments can achieve alone.

What evidence suggests that this trial's treatments could be effective for dyslipidemia?

Studies have shown that obicetrapib effectively lowers certain bad cholesterol levels and significantly increases good cholesterol by up to 165%, suggesting it could improve heart health. Evolocumab, a cholesterol-lowering drug, has reduced levels of a specific type of cholesterol linked to heart disease risks. This trial tests the combination of obicetrapib and evolocumab to determine if it can further lower these harmful cholesterol levels. Early research suggests this combination could strongly manage unhealthy cholesterol levels. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Obicetrapib

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06496243

Study Details | NCT06496243 | Impact of Obicetrapib and ... To evaluate the effect of evolocumab in combination with obicetrapib on lipoprotein (a) (Lp[a]). Lp(a) change on combination therapy, 16 weeks from baseline; 8 ...

2. withpower.com withpower.com/trial/obicetrapib-repatha-for-dyslipidemia-9fcbc

Obicetrapib + Repatha for Dyslipidemia (VINCENT Trial) Obicetrapib also decreased apolipoprotein B and non-HDL cholesterol levels while increasing HDL cholesterol by up to 165%, demonstrating its potential as an ...

3. ctv.veeva.com ctv.veeva.com/study/impact-of-obicetrapib-and-obicetrapib-plus-repatha-on-lp-a-levels

Impact of Obicetrapib and Obicetrapib Plus Repatha on Lp(a ... 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/ ...

4. trialx.com trialx.com/clinical-trials/listings/324280/impact-of-obicetrapib-and-obicetrapib-plus-repatha-on-lpa-levels/

Impact of Obicetrapib and Obicetrapib Plus Repatha on Lp ... Overview. The goal of this open label 16 week trial is to evaluate Lp(a) levels for patients with elevated Lp(a) being treated with ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666667724000692

Advances in targeting LDL cholesterol: PCSK9 inhibitors ... A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J ... obicetrapib in combination with high-intensity statins: a randomized phase 2 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11278114/

Advances in targeting LDL cholesterol: PCSK9 inhibitors ... Obicetrapib has been studied in combination with high-intensity statins and ezetimibe [111]. The most prevalent adverse events were gastrointestinal disorders ( ...

7. clinicaltrials.eu clinicaltrials.eu/inn/obicetrapib/

Obicetrapib – Application in Therapy and Current Clinical ... With evolocumab (Repatha): A study is examining how obicetrapib works when combined with evolocumab, a different class of cholesterol medication. These ...

8. researchgate.net researchgate.net/publication/391995354_LDL-cholesterol_lowering_with_obicetrapib

LDL-cholesterol lowering with obicetrapib Results Of the 1090 patients, 140 (13%) had HeFH by clinical diagnostic criteria and/or CVD with LDLC >100 mg/dL despite ≥2 months on MTDLLT, ...