Rilonacept to Improve Artery Function in Patients With Atherosclerosis

• Status: Completed
• Trial end date: 2008-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Rilonacept

Criteria

• INCLUSION CRITERIA:

• Male and non-pregnant female subjects over 18 years of age

• Diagnosis of atherosclerotic CAD by coronary angiography

• High sensitivity C-reactive protein (hsCRP) between 2.0 and 10.0 g/L, inclusive with percent change in CRP from Visit 1 to Visit 2 of less than 50% to +100%.

• Taking a HMG-CoA reductase inhibitor -For men and women of childbearing potential, willingness to utilize adequate contraception

• Willing, at time of study enrollment, to return for all clinic visits specified in the protocol and complete all study-related procedures.

EXCLUSION CRITERIA:

• BMI (body mass index) greater than 49.9 kg/m2 at Screening Visit 1 -Vascular intervention within 60 days prior to Screening Visit 1.

• Infection, use of systemic antibiotics, or clinically significant trauma (including surgery) within 30 days prior to Screening Visit 1.

• History or evidence of acute coronary syndrome within 60 days prior to Screening Visit 1.

• Acute or chronic inflammatory condition other than atherosclerosis

• Recently diagnosed diabetes mellitus

• Clinical evidence of congestive heart failure NYHA Class III-IV

• History of hypersensitivity other than localized injection site reaction to any biologic agent.

• Use of a thiazolidinedione

• Use of immunosuppressive or immunomodulatory medication (use of an inhaled glucocorticoid is permitted).

• Prior use of an immunomodulatory biologic drug within the last 6 months except immunizations and biologics used as standard care in cardiac care settings.

• Received a live/live attenuated vaccine within 90 days prior to Screening Visit 1 or other immunization within 30 days prior to Screening Visit 1.

• Prior or planned organ transplant recipient.

• Severe respiratory disease

• A history of tuberculosis infection, history of a positive skin test for tuberculosis, or a chest radiograph at Screening Visit 1 consistent with prior tuberculosis infection

• Positive result (5 mm or more in duration at 48 to 72 hours post-placement) of the PPD 5 TU placed at Screening Visit 2

• History or presence of malignancy (except for successfully treated basal cell carcinoma of the skin or in situ carcinoma of the cervix) within the past 5 years.

• HIV positive.

• Hepatitis B surface antigen or Hepatitis C antibody positive

• ALT, AST or alkaline phosphatase greater than twice the upper limit of the normal range, serum creatinine or total bilirubin greater than 1.5 times the upper limit of normal at Screening Visit 1.

• Hemoglobin less than 11.0 gm/dL, white blood cell (WBC) count less than 3,000/mm3, neutrophil count less than 2000/mm3 or platelet count less than 100,000/mm3 at Screening Visit 1.

• Participation in any clinical research study evaluating another investigational drug or therapy within 30 days prior to Screening Visit 1.

• History of substance abuse

• Elective surgery or vascular intervention planned to occur during the study.

• Any medical condition which would interfere with participation in the study, interfere with interpretation of study outcome measures, or place the subject at risk.