Obicetrapib + Ezetimibe for Coronary Artery Disease

(REMBRANDT Trial)

Overseen By Claudia Forkel

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NewAmsterdam Pharma

Must be taking: Lipid-modifying therapy

Disqualifiers: Diabetes, Liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This placebo-controlled, double-blind, randomized, Phase 3 study is being conducted in adult participants with high-risk atherosclerotic cardiovascular disease (ASCVD) who are not adequately controlled by their maximally tolerated lipid-modifying therapy, to assess the impact of the obicetrapib 10 mg + ezetimibe 10 mg FDC daily on coronary plaque and inflammation characteristics, evaluated using cardiovascular computed tomography angiography (CCTA).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that participants should be on their maximum tolerated lipid-modifying therapy. This suggests you may need to continue your current lipid-modifying medications.

Is the combination of Obicetrapib and Ezetimibe safe for humans?

Research shows that Obicetrapib, when used with high-intensity statins, has an acceptable safety profile in patients with high cholesterol. Ezetimibe has also been evaluated for safety in various studies, including when combined with other cholesterol-lowering medications, and is generally considered safe. ^{1 2 3 4 5}

What makes the drug Obicetrapib/Ezetimibe unique for treating coronary artery disease?

The drug Obicetrapib/Ezetimibe is unique because it combines two components that work together to lower cholesterol levels, which is a key factor in managing coronary artery disease. This combination may offer a novel approach compared to traditional treatments that often focus on single mechanisms or require more invasive procedures like percutaneous coronary intervention (PCI). ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults with high-risk heart-related artery disease who aren't responding well to their current cholesterol-lowering treatments. They should have a certain amount of plaque in their arteries, a body mass index between 18-40, proper kidney function, and LDL cholesterol over 70mg/dL.

Inclusion Criteria

My LDL cholesterol is above 70 mg/dL.

My kidney function is normal or only mildly reduced.

My heart's arteries have significant plaque buildup.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive obicetrapib 10 mg + ezetimibe 10 mg FDC daily or placebo for 18 months

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Obicetrapib/Ezetimibe

Trial Overview The study tests if taking obicetrapib plus ezetimibe daily can change the characteristics of coronary plaque and inflammation. This is measured using advanced heart scans (CCTA). Participants are randomly chosen to either receive this combination or a placebo without knowing which one they get.

Participant Groups

Group I: Obicetrapib/Ezetimibe Experimental Treatment 1 Intervention

obicetrapib 10 mg + ezetimibe 10 mg FDC daily

Group II: Placebo Placebo Group 1 Intervention

Placebo on top of baseline lipid modifying therapy

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]

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]

In a phase IV clinical trial involving patients with atherosclerotic cardiovascular disease (ASCVD), the combination therapy of moderate-intensity rosuvastatin and ezetimibe significantly reduced LDL cholesterol levels more than high-intensity rosuvastatin alone after 12 and 24 weeks.

The combination therapy also resulted in a higher percentage of patients reaching the target LDL-C level of ≤70 mg/dL, while maintaining a similar safety profile with no significant increase in adverse events compared to the monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid-Lowering Efficacy of Combination Therapy With Moderate-Intensity Statin and Ezetimibe Versus High-Intensity Statin Monotherapy: A Randomized, Open-Label, Non-Inferiority Trial From Korea. Choi, H., Kang, SH., Jeong, SW., et al.[2023]

In a study of 144 patients with coronary artery disease, coadministering ezetimibe with simvastatin led to a significant additional reduction in LDL cholesterol levels by 17.6% compared to simvastatin alone after 6 weeks.

The combination therapy also resulted in more patients reaching the target LDL cholesterol levels set by the National Cholesterol Education Program (70% vs. 33% for simvastatin alone), and it was well tolerated with a safety profile similar to simvastatin monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ezetimibe coadministration with simvastatin in a Middle Eastern population: a prospective, multicentre, randomized, double-blind, placebo-controlled trial. Zubaid, M., Shakir, DK., Bazargani, N., et al.[2015]

In a study of 827 patients with primary hypercholesterolemia, ezetimibe 10 mg/day significantly reduced low-density lipoprotein cholesterol (LDL-C) by an average of 17.7% compared to a 0.8% increase with placebo, demonstrating its efficacy in lowering cholesterol levels.

Ezetimibe was well tolerated and had a safety profile similar to placebo, without affecting lipid-soluble vitamins or cortisol production, suggesting it is a safe option for managing cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Knopp, RH., Gitter, H., Truitt, T., et al.[2019]

Percutaneous coronary intervention (PCI) has significantly improved in safety and efficacy over the past two decades due to advancements like drug-eluting stents and better pharmacological support, enhancing procedural success and long-term outcomes.

Despite these improvements, there is a growing concern about increased mortality associated with drug-eluting stents, prompting physicians to follow FDA guidelines until further studies clarify this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous coronary intervention: the story so far. Martinez-Ojeda, J., Martinez-Toro, J.[2010]

Coronary artery disease (CAD) is a leading cause of illness and death in the U.S., and its diagnosis involves a combination of clinical exams, noninvasive techniques, and catheterization.

Effective treatment options for CAD include a range of medications like aspirin and beta-blockers, as well as procedures like angioplasty and bypass surgery, with an emphasis on personalized care based on recent clinical trial findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and management of coronary artery disease. Blanchard, A., Pfeffer, MA.[2019]

In a study of 299 patients undergoing elective PCI or NSTEMI, administering a P2Y12 inhibitor only after coronary angiography resulted in a low incidence of major ischemic events (8.5%) and no cases of definite stent thrombosis within 30 days.

The approach was associated with a clinically relevant bleeding rate of 5.4%, suggesting that this 'on-the-table' loading strategy is both safe and effective in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Percutaneous Coronary Intervention Without P2Y12 Inhibitor Pretreatment From a Cohort of Unselected Patients. Lattuca, B., Belardi, D., Demattei, C., et al.[2018]

Dual antiplatelet therapy with aspirin and clopidogrel is commonly used during percutaneous coronary intervention (PCI) to prevent complications, but individual responses can vary due to genetic factors and other influences.

Newer oral antiplatelet agents like prasugrel and ticagrelor offer greater effectiveness in reducing ischaemic events but are associated with a higher risk of bleeding, highlighting the need for careful risk assessment when selecting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiplatelet therapy in percutaneous coronary intervention: recent advances in oral antiplatelet agents. Wong, YW., Prakash, R., Chew, DP.[2018]

In a study of 109 patients with acute coronary syndrome who underwent percutaneous coronary intervention, both ticagrelor and clopidogrel showed comparable effectiveness in preventing ischemic events, with no significant differences in stent thrombosis rates.

However, ticagrelor was associated with a higher frequency of minor bleeding compared to clopidogrel, which demonstrated better hemorrhagic safety, particularly in terms of fatal bleeding incidents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Double antiplatelet therapy in patients with acute coronary syndrome after percutaneous coronary intervention: individual efficacy and hemorrhagic safety of P2Y12 blockers of ticagrelor and clopidogrel in actual clinical practice]. Korotaeva, ES., Koroleva, LY., Kovaleva, GV., et al.[2019]

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

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

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Lipid-Lowering Efficacy of Combination Therapy With Moderate-Intensity Statin and Ezetimibe Versus High-Intensity Statin Monotherapy: A Randomized, Open-Label, Non-Inferiority Trial From Korea. [2023]

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

Effect of ezetimibe coadministration with simvastatin in a Middle Eastern population: a prospective, multicentre, randomized, double-blind, placebo-controlled trial. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. [2019]

6. Puerto Rico pubmed.ncbi.nlm.nih.gov

Percutaneous coronary intervention: the story so far. [2010]

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

Diagnosis and management of coronary artery disease. [2019]

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

Safety of Percutaneous Coronary Intervention Without P2Y12 Inhibitor Pretreatment From a Cohort of Unselected Patients. [2018]

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

Antiplatelet therapy in percutaneous coronary intervention: recent advances in oral antiplatelet agents. [2018]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Double antiplatelet therapy in patients with acute coronary syndrome after percutaneous coronary intervention: individual efficacy and hemorrhagic safety of P2Y12 blockers of ticagrelor and clopidogrel in actual clinical practice]. [2019]