Evolocumab for Heart Disease

(VESALIUS-CV Trial)

Recruiting at 859 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must not be taking: Anticoagulants

Disqualifiers: MI, Stroke, CABG, 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: Approximately 4.5 years

12301 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study will assess the effect of lowering low-density lipoprotein cholesterol (LDL-C) with evolocumab on major cardiovascular events in adults without a prior myocardial infarction (MI) or stroke who are at high risk of a cardiovascular event.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have atrial fibrillation or atrial flutter, you must be on anticoagulation therapy to participate.

Is Evolocumab safe for humans?

The ZERBINI study analyzed Evolocumab's use in real-world settings for patients with high cholesterol and assessed its safety, indicating it is generally safe for human use. ^{1 2 3 4 5}

How is the drug Evolocumab unique for treating heart disease?

Evolocumab is unique because it is a monoclonal antibody that specifically targets and inhibits a protein called PCSK9, which helps lower LDL cholesterol (often called 'bad' cholesterol) levels in the blood. This mechanism is different from traditional cholesterol-lowering drugs like statins, which work by reducing cholesterol production in the liver. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Evolocumab for heart disease?

The ZERBINI study shows that Evolocumab is effective in treating patients with high cholesterol, which is a risk factor for heart disease. This suggests that Evolocumab may help reduce heart disease risk by lowering cholesterol levels. ^{1 11 12 13 14}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults aged 50-80 without a history of heart attack or stroke but at high risk for cardiovascular events. They must have high levels of LDL-C or other lipid markers and evidence of significant coronary, cerebrovascular, peripheral arterial disease, or diabetes with at least one high-risk feature.

Inclusion Criteria

I am a man over 50 or a woman over 55, but under 80, and meet the cholesterol guidelines.

I have significant heart, brain, or leg artery disease, or diabetes.

You have at least one significant risk factor.

Exclusion Criteria

Your triglyceride levels are higher than 500 mg/dL in the past 3 months.

I have not had a heart bypass surgery in the last 3 months.

My heart's pumping ability is very weak.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 140 mg evolocumab or placebo by subcutaneous injection every 2 weeks

Approximately 4.5 years

Bi-weekly visits for injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Evolocumab
• Placebo

Trial Overview The study tests the effect of Evolocumab on preventing major cardiovascular events compared to a placebo in individuals with no prior myocardial infarction or stroke but who are considered at high risk due to their cholesterol levels.

How Is the Trial Designed?

Group I: Evolocumab 140 mg Q2W Experimental Treatment 1 Intervention

Participants will receive 140 mg evolocumab by subcutaneous injection Q2W.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo subcutaneous injection once every 2 weeks (Q2W).

Evolocumab is already approved in United States, European Union for the following indications:

Approved in United States as Repatha for:

• To reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease
• Familial hypercholesterolemia
• High-risk patients with LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL on maximally tolerated statin therapy ± ezetimibe

Approved in European Union as Repatha for:

• Primary hypercholesterolaemia and mixed dyslipidaemia
• Homozygous familial hypercholesterolaemia

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

Celacade treatment in rats significantly reduced the production of transforming growth factor beta-1 in the heart after a myocardial infarction, indicating its potential to modulate inflammatory responses during acute heart injury.

While Celacade did not prevent chronic cardiac dilation following myocardial infarction, it successfully restored the heart's ability to contract more forcefully and reduced diastolic dysfunction, suggesting it may improve heart function post-injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of therapy using the Celacade system on structural and functional cardiac remodelling in rats following myocardial infarction. Zhang, ML., Mei, J., Archer, LA., et al.[2021]

Research shows that the immune system plays a crucial role in the development and progression of atherosclerosis, with elevated blood markers of inflammation linked to higher risks of cardiovascular events.

While existing treatments like statins suggest that modifying immune responses could improve cardiovascular outcomes, more robust clinical trials are needed to confirm the effectiveness of targeted anti-inflammatory therapies in managing atherosclerotic vascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inflammation and atherosclerosis: disease modulating therapies. Patel, MJ., Blazing, MA.[2021]

The immune system plays a crucial role in heart failure, yet it is often overlooked as a target for treatment, which could limit the effectiveness of current therapies.

Current heart failure treatments have various immunomodulatory effects beyond their primary actions, suggesting that understanding these effects could help develop new immunomodulatory therapies tailored for specific patient subpopulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation and immunopharmacology in heart failure. Markousis-Mavrogenis, G., Baumhove, L., Al-Mubarak, AA., et al.[2023]

Placebo-controlled trials are essential in clinical research as they help establish the efficacy of new treatments, but their use has come under scrutiny when effective alternatives are available.

The paper discusses the ethical implications of using placebo controls, emphasizing that while they provide valuable data, their appropriateness can vary depending on the medical context and existing treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 2: practical issues and specific cases. Ellenberg, SS., Temple, R.[2019]

In a multicenter trial involving 34 patients with Takayasu arteritis, the addition of abatacept to prednisone treatment did not significantly improve relapse-free survival compared to placebo, with rates of 22% for abatacept and 40% for placebo at 12 months.

There were no significant differences in the frequency or severity of adverse events, including infections, between the abatacept and placebo groups, indicating that abatacept is safe but ineffective in prolonging remission in Takayasu arteritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis. Langford, CA., Cuthbertson, D., Ytterberg, SR., et al.[2018]

In a multicenter trial involving 49 patients with giant cell arteritis (GCA), the addition of abatacept to a prednisone regimen significantly improved relapse-free survival rates at 12 months (48% for abatacept vs. 31% for placebo).

Patients receiving abatacept also experienced a longer median duration of remission (9.9 months) compared to those on placebo (3.9 months), with no increase in adverse events, indicating that abatacept is both effective and safe for treating GCA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. Langford, CA., Cuthbertson, D., Ytterberg, SR., et al.[2022]

This study protocol outlines a 52-week trial involving 206 participants to evaluate the effectiveness of abatacept, a co-stimulatory blocker, in preventing or delaying inflammatory arthritis in individuals at risk for rheumatoid arthritis (RA).

The trial is designed to rigorously assess the time to develop significant joint swelling, with all participants and assessors blinded to treatment assignments, ensuring unbiased results in determining the efficacy of abatacept compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol. Al-Laith, M., Jasenecova, M., Abraham, S., et al.[2023]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Effects of therapy using the Celacade system on structural and functional cardiac remodelling in rats following myocardial infarction. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Real-World Insights into Evolocumab Use in Patients with Hyperlipidemia Across Five Countries: Analysis from the ZERBINI Study. [2023]

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

Inflammation and atherosclerosis: disease modulating therapies. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Immunomodulation and immunopharmacology in heart failure. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy in HFrEF]. [2021]

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

Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 2: practical issues and specific cases. [2019]

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

Historical control monotherapy design in the treatment of epilepsy. [2010]

8. England pubmed.ncbi.nlm.nih.gov

Current trends in the cardiovascular clinical trial arena (I). [2023]

9. England pubmed.ncbi.nlm.nih.gov

Transitioning to active-controlled trials to evaluate cardiovascular safety and efficacy of medications for type 2 diabetes. [2022]

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

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis. [2018]

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

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Effects of golimumab, an anti-tumour necrosis factor-α human monoclonal antibody, on lipids and markers of inflammation. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol. [2023]

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

Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. [2022]