Rilonacept to Improve Artery Function in Patients With Atherosclerosis

Summary

This study will determine whether an experimental drug called Rilonacept can improve artery function in patients with atherosclerosis, a disease in which fatty deposits in arteries cause the vessels to stiffen, impeding blood flow. Atherosclerosis is believed to be caused in part by inflammation. Rilonacept blocks production of a protein called CRP, which, in high levels in the blood is associated with increased inflammation. Patients with coronary artery disease who have elevated blood levels of CRP are at increased risk of heart attack, heart failure and sudden death compared with people who have lower levels of the protein.

Patients 18 years of age and older with atherosclerotic coronary artery disease with a CRP level between 2 and 10 mg/L may be eligible for this study.

Patients are randomly assigned to receive four doses of either Rilonacept or placebo, given at 2-week intervals as injections under the skin. In addition to treatment, patients undergo the following procedures during eight visits to the NIH Clinical Center:

* Visit 1 (screening visit): Medical history, measurement of vital signs (temperature, blood pressure, heart rate and breathing rate), electrocardiogram (EKG) and blood tests.
* Visit 2: Blood tests, chest X-ray, treadmill exercise testing, tuberculin skin test, brachial artery flow-mediated dilation. Brachial artery flow-mediated dilation is used to measure how well the brachial artery (artery inside the elbow) dilates. An ultrasound device placed just above the elbow measures the size of the brachial artery and the flow of blood through it before and after a pressure cuff is inflated around the forearm.
* Visit 3: Injection of study drug.
* Visits 4, 5, and 6: Review of any changes in health or medical treatment, measurement of vital signs, blood tests, EKG, injection of study drug.
* Visit 7: Review of any changes in health or medical treatment, measurement of vital signs, blood tests, EKG, treadmill exercise testing, brachial artery flow-mediated dilation.
* Visit 8: Review of any changes in health or medical treatment, measurement of vital signs, blood tests, EKG, treadmill exercise testing, brachial artery flow-mediated dilation.

Conditions

• Coronary Artery Disease
• Atherosclerosis
• Inflammation
• Endothelial Dysfunction

Interventions

DRUG

Rilonacept

Lyophilized rilonacept will be supplied by Regeneron Pharmaceuticals at 160 mg/vial and reconstituted with 2.3 mL of sterile water for injection by the Clinical Center Pharmacy Intravenous Admixture Unit. The formulation contains 80 mg/mL rilonacept, histidine, citrate, PEG 3350, polysorbate 20, glycine, arginine, and sucrose (pH 6.5). Matching placebo in the identical formulation will also be supplied, and also reconstituted with 2.3 mL of sterile water for injection. Each administration of study drug will consist of two syringes containing 2.0 mL in each syringe (320 mg total drug).

DRUG

Placebo

Normal saline subcutaneously at each treatment visit.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  lead NIH

Principal Investigators

• Richard O Cannon, MD · NHLBI, NIH

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-12-31

Primary Completion

2008-04-30

Completion

2008-04-30

Countries

• United States

Study Locations