Mechanistic Clinical Trial of PCSK9 Inhibition for AAA

NCT06081153 | Not Yet Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: 852428R01HL166991
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Abdominal Aortic Aneurysm

Outcome Measures

Primary Outcomes (1)

• Interleukin (IL)-6 in myeloid derived monocytes/macrophages from in AAA tissue

  IL-6 expression will be measured in myeloid cells in the aortic tissue specimens using single nucleus RNA sequencing and confirmed by whole tissue ELISA.

  AAA Repair (Week 5)

Secondary Outcomes (3)

• Matrix metalloproteinase (MMP)-9 in myeloid derived monocytes/macrophages from in AAA tissue

  AAA Repair (Week 5)

• Infiltrating immune cell composition and their activation/inflammatory states in AAA tissue

  AAA Repair (Week 5)

• Smooth muscle composition of AAA tissue

  AAA Repair (Week 5)

Study Arms (2)

Evolocumab

EXPERIMENTAL

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).

Drug: Evolocumab

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Evolocumab DRUG

See arm description.

Evolocumab

Placebo DRUG

See arm description.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Abdominal aortic aneurysm (AAA) requiring open surgical repair
• Age \> 18
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study

You may not qualify if:

• Prior use of a PCSK9 inhibitor (evolocumab, alirocumab, inclisiran) within 6 months of the baseline visit
• LDL-C \< 40 mg/dL (within 3 months of baseline visit)
• Known allergy to PCSK9 inhibitor
• Aortic dissection
• Vascular connective tissue disorders
• Type I-III or V Thoraco-abdominal Aortic Aneurysm
• Vasculitis or inflammatory aneurysm
• Pregnant or lactating women
• Poorly controlled diabetes (A1C \> 10%)
• Chronic kidney disease Stage 4/5 or End Stage Renal Disease (ESRD) on hemodialysis (HD)
• Liver Disease (alanine transaminase \[ALT\] or aspartate aminotransferase \[ALT\] \> 3.0 x upper limits of normal) (within 3 months of baseline visit)
• Known latex or naturally rubber allergy
• 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.
• Any other condition that the Investigator feels prohibits participants' ability to comply with study or follow up.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Amgen: collaborator

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19010, United States

Location

MeSH Terms

Conditions

Aortic Aneurysm, Abdominal

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Aortic Aneurysm; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases

Study Officials

• Scott Damrauer, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Scott Damrauer, MD

CONTACT

215-615-1698; damrauer@upenn.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Surgery

Study Record Dates

• First Submitted: October 3, 2023
• First Posted: October 13, 2023
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): January 15, 2029
• Study Completion (Estimated): February 28, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)