Evolocumab for Coronary Heart Disease

(EMPOWER Trial)

Overseen By Leanne Barrett

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Brigham and Women's Hospital

Must be taking: PCSK-9 inhibitors

Must not be taking: PCSK-9 inhibitors

Disqualifiers: Myocardial infarction, Stroke, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 52 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The study protocol is a single-arm, open label pilot study designed to evaluate the impact of PCSK-9 inhibition on coronary blood flow in patients with stable coronary artery disease. Patients with stable coronary artery disease will be recruited from the BWH Cardiovascular Medicine clinic and/or from the BWH Nuclear Cardiology Laboratory. A target sample size of 50 participants will undergo imaging with N-13 ammonia or Rubidium-82 positron emission tomography (PET) and coronary computed tomography angiography (CCTA) before and after 12 months of PCSK-9 inhibition with Evolocumab to assess changes in myocardial blood flow, and plaque volume. To help account for physiological changes that may occur in myocardial blood flow and inflammatory biomarkers during the study period, we will also recruit a parallel control group of stable CAD patients who will undergo similar baseline and 12-month imaging and biomarker assessment. We plan to recruit 15 patients in the parallel control group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on a statin, you must be on a stable dose for at least 3 months before joining the study.

How is the drug Evolocumab unique for treating coronary heart disease?

Evolocumab is unique because it is a monoclonal antibody that targets a specific protein (PCSK9) to help the liver remove more LDL cholesterol from the blood, which is different from traditional treatments like statins. It is administered through an injection, either every two weeks or once a month, and is particularly useful for patients who cannot tolerate statins or need additional help lowering their cholesterol. ^{1 2 3 4 5}

Who Is on the Research Team?

Diana Lopez, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 50 (men) or 55 (women) with stable coronary artery disease and LDL cholesterol ≥70 mg/dL. They must not be planning revascularization soon, have been on a steady statin dose for 3+ months if applicable, and meet certain criteria indicating heart issues. Excluded are pregnant/breastfeeding individuals, those with severe heart conditions, kidney failure, contraindications to vasodilators, recent major cardiac events or procedures, specific genetic disorders affecting cholesterol levels, severe heart failure or angina.

Inclusion Criteria

You have a high score indicating calcium buildup in your arteries.

Your nuclear perfusion imaging results are not normal.

You have widespread clogging of the arteries in three main areas of the body.

Exclusion Criteria

Your fasting triglyceride levels are higher than 500 mg/dL.

I have a serious heart valve problem.

Currently pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline rest/stress cardiac PET scan along with CCTA

1 week

1 visit (in-person)

Treatment

Participants receive PCSK-9 inhibition with Evolocumab for 12 months

52 weeks

Regular visits as per protocol

Follow-up

Participants undergo final PET scan and CCTA to assess changes in myocardial blood flow and plaque volume

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Evolocumab

Trial Overview The study tests the effect of Evolocumab on blood flow in coronary arteries using PET scans and CCTA imaging before and after a year of treatment. It's an open-label pilot study where all participants receive the drug; there's also a control group without the drug to compare changes in myocardial blood flow and plaque volume.

How Is the Trial Designed?

Group I: Evolocumab Experimental Treatment 1 Intervention

Informed consent will be obtained from study participants willing to participate in EMPOWER. Study participants will then undergo the baseline rest/stress cardiac PET scan along with CCTA. The final PET scan and CCTA will occur at 12 months after the intervention.

Group II: Control Active Control 1 Intervention

Informed consent will be obtained from study participants willing to participate in EMPOWER. Study participants will then undergo the baseline rest/stress cardiac PET scan along with CCTA. The final PET scan and CCTA will occur at 12 months after the baseline.

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?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

Evolocumab (Repatha™) is an effective treatment for hypercholesterolaemia, approved in the EU and awaiting approval in the USA and Japan, that works by binding to PCSK9, enhancing the liver's ability to remove LDL-cholesterol from the blood.

The drug can be used alone or alongside statins and other lipid-lowering therapies, showing efficacy in both adults and adolescents with various forms of hypercholesterolaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolocumab: First Global Approval. Markham, A.[2020]

Evolocumab (Repatha(®)) is an effective injectable treatment for patients with familial hypercholesterolemia or statin intolerance, helping to significantly lower LDL cholesterol levels when statins alone are insufficient.

The review highlights the safety and efficacy of evolocumab based on results from various clinical trials, indicating its potential role as a second-line therapy after maximally tolerated statin therapy and lifestyle changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: evolocumab. Dahagam, C., Goud, A., Abdelqader, A., et al.[2021]

Evolocumab (Repatha) is an FDA-approved PCSK9 inhibitor that can reduce LDL-cholesterol levels by approximately 60% in high-risk patients already on maximum statin therapy, showing similar efficacy and safety to another PCSK9 inhibitor, alirocumab (Praluent).

The long-term effects of evolocumab on cardiovascular outcomes and its overall safety profile are still not fully established, and both evolocumab and alirocumab are considered expensive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolocumab (Repatha)--a second PCSK9 inhibitor to lower LDL-Cholesterol. [2019]

Evolocumab is a monoclonal antibody that significantly reduces LDL cholesterol levels in patients with primary hypercholesterolemia and mixed dyslipidemia, showing treatment differences of 54.8% to 76.3% compared to placebo and 36.9% to 47.2% compared to ezetimibe over 12-week trials.

It is effective even in patients who are statin-intolerant or have homozygous familial hypercholesterolemia, maintaining its efficacy over the long term and demonstrating good tolerability, making it a valuable treatment option for those who struggle to achieve LDL-C goals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolocumab: A Review in Hyperlipidemia. Keating, GM.[2019]

Evolocumab, a PCSK9 inhibitor, can significantly improve cardiovascular outcomes in high-risk patients, but its effectiveness can be compromised by improper injection techniques.

In a case study of a 41-year-old woman with familial hypercholesterolemia, her lack of response to the PCSK9 inhibitor was traced back to incorrect subcutaneous injection, emphasizing the need to ensure proper administration before considering genetic testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Small Change Can Make a Big Difference: A Lesson from Evolocumab. Mirzaee, S., Thein, PM., Wong, D., et al.[2021]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

Evolocumab: First Global Approval. [2020]

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

PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: evolocumab. [2021]

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

Evolocumab (Repatha)--a second PCSK9 inhibitor to lower LDL-Cholesterol. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Evolocumab: A Review in Hyperlipidemia. [2019]

5. Australia pubmed.ncbi.nlm.nih.gov

A Small Change Can Make a Big Difference: A Lesson from Evolocumab. [2021]