Mechanistic Clinical Trial of PCSK9 Inhibition for AAA

NCT ID: NCT06081153

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-07-01
• Study Completion Date: 2028-02-28

Brief Summary

The goal of this mechanistic clinical trial is to assess whether lowering the low-density lipoprotein cholesterol (LDL-C) levels in the blood with the injections of the medication evolocumab will have any effect on the tissue or cells of patients with abdominal aortic aneurysm (AAA). Researchers will compare participants receiving evolocumab injections to participants receiving placebo injections to see how the tissue and cells of the aorta are affected by changes in LDL-C levels.

Detailed Description

After being informed about the study and its potential risks, all patients giving informed consent will undergo a baseline visit and be randomized to received either evolocumab 140mg subcutaneously or placebo. This baseline visit includes a vital signs assessment, laboratory tests, medical history and medication review, a pregnancy test (if applicable), and training on how to perform drug injections. Participants will receive 3 doses/autoinjectors of study drug or placebo and be instructed to perform injections every 14 days starting 5 weeks prior to their scheduled AAA repair. If the baseline assessment occurs 5 weeks prior to their scheduled AAA, the first injection will be performed during this visit. Participants will have the option of coming back to the site for injections 2 and 3 or perform these injections at home under telehealth supervision. At the time of open AAA repair, participants will repeat laboratory tests and have a sample of aneurysm tissue taken. Participants will then have a follow up phone call 4 weeks after AAA repair to assess for any adverse events. At the conclusion of the study investigators will examine gene expression and protein levels in the aortic tissue to determine the impact of LDL-C lowering with evolocumab.

Conditions

Abdominal Aortic Aneurysm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Evolocumab

Evolocumab is the drug that will be administered in this study. It will be administered as a 140mg subcutaneous injection every 14 days for 5 weeks (for a total of 3 doses).

Group Type: EXPERIMENTAL

Evolocumab

Intervention Type: DRUG

See arm description.

Placebo

This arm is a matching placebo that will be administered in the same fashion as the study drug if the patient is randomized to placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

See arm description.

Interventions

Evolocumab

See arm description.

Intervention Type: DRUG

Placebo

See arm description.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Abdominal aortic aneurysm (AAA) requiring open surgical repair

2. Age > 18

3. Provision of signed and dated informed consent form

4. Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

1. Prior use of a PCSK9 inhibitor (evolocumab, alirocumab, inclisiran) within 6 months of the baseline visit

2. LDL-C < 40 mg/dL (within 3 months of baseline visit)

3. Known allergy to PCSK9 inhibitor

4. Aortic dissection

5. Vascular connective tissue disorders

6. Type I-III or V Thoraco-abdominal Aortic Aneurysm

7. Vasculitis or inflammatory aneurysm

8. Pregnant or lactating women

9. Poorly controlled diabetes (A1C > 10%)

10. Chronic kidney disease Stage 4/5 or End Stage Renal Disease (ESRD) on hemodialysis (HD)

11. Liver Disease (alanine transaminase [ALT] or aspartate aminotransferase [ALT] > 3.0 x upper limits of normal) (within 3 months of baseline visit)

12. Known latex or naturally rubber allergy

13. Treatment with another investigational product within 30 days or 5 half-lives of the investigation drug before consent (whichever is longer) that would have an impact on endpoints associated with this trial.

14. Any other condition that the Investigator feels prohibits participants' ability to comply with study or follow up.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Scott Damrauer

Associate Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Scott Damrauer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Central Contacts

Scott Damrauer, MD

Role: CONTACT

damrauer@upenn.edu

215-615-1698

Other Identifiers

R01HL166991

Identifier Type: NIH

Identifier Source: secondary_id

View Link

852428

Identifier Type: -

Identifier Source: org_study_id