Rilonacept to Improve Artery Function in Patients With Atherosclerosis

NCT00417417 | Completed Phase 2 Results DMC

• 2 other identifiers: 07005507-H-0055
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Endothelium; Inflammation; Nitric Oxide; Rilonacept; Cytokines; Coronary Artery Disease; CAD; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• C-Reactive Protein (CRP)

  C-reactive protein levels in subjects randomized to rilonacept versus placebo injections.

  2 wks following last drug administration

Other Outcomes (1)

• Brachial Artery Flow-mediated Dilation

  Two weeks following final administration of drug

Study Arms (2)

Rilonacept

EXPERIMENTAL

Rilonacept 320 mg subcutaneous at each treatment visit

Drug: Rilonacept

Placebo

SHAM COMPARATOR

Normal saline subcutaneously at each treatment visit.

Drug: Placebo

Interventions

Rilonacept DRUG

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).

Also known as: Arcalyst (brand name)

Rilonacept

Placebo DRUG

Normal saline subcutaneously at each treatment visit.

Also known as: normal saline

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996 Mar 15;87(6):2095-147.

  PMID: 8630372 BACKGROUND

• 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.

  PMID: 8332913 BACKGROUND

• 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.

  PMID: 16470011 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease; Atherosclerosis; Inflammation

Interventions

rilonacept; Saline Solution

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Richard O. Cannon III, MD
• Organization: NHLBI/NIH

cannonr@nih.gov

301-496-9895

Study Officials

• Richard O Cannon, MD

  NHLBI, NIH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: senior investigator, NHLBI Division of Inrtramural Research

Study Record Dates

• First Submitted: December 29, 2006
• First Posted: January 1, 2007
• Study Start: December 1, 2006
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: April 30, 2012
• Results First Posted: April 13, 2010

Record last verified: 2012-04

Locations

US (1)