- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00417417
Rilonacept to Improve Artery Function in Patients With Atherosclerosis
Effects of Interleukin-1 Inhibition on C-Reactive Protein Levels, Endothelial Progenitor Cell Mobilization and Endothelial Function in Patients With Coronary Artery Disease
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.
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Rilonacept
Rilonacept 320 mg subcutaneous at each treatment visit
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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).
Other Names:
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Sham Comparator: Placebo
Normal saline subcutaneously at each treatment visit.
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Normal saline subcutaneously at each treatment visit.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
C-Reactive Protein (CRP)
Time Frame: 2 wks following last drug administration
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C-reactive protein levels in subjects randomized to rilonacept versus placebo injections.
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2 wks following last drug administration
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brachial Artery Flow-mediated Dilation
Time Frame: Two weeks following final administration of drug
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Brachial artery flow-mediated dilation in respone to 5 minutes of forearm ischemia
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Two weeks following final administration of drug
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Collaborators and Investigators
Investigators
- Principal Investigator: Richard O Cannon, MD, NHLBI, NIH
Publications and helpful links
General Publications
- Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996 Mar 15;87(6):2095-147.
- Colotta F, Re F, Muzio M, Bertini R, Polentarutti N, Sironi M, Giri JG, Dower SK, Sims JE, Mantovani A. Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science. 1993 Jul 23;261(5120):472-5. doi: 10.1126/science.8332913.
- Dinarello CA. Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. Am J Clin Nutr. 2006 Feb;83(2):447S-455S. doi: 10.1093/ajcn/83.2.447S.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 070055
- 07-H-0055 (Other Identifier: NIH Clinical Center protocol 07-H-0055)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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