Silencing Inflammatory Activity by Injecting Nanocort in Patients at Risk for Atherosclerotic Disease (SILENCE)

Inclusion Criteria:

• Population with target to background ratio of 2.2 of the aorta or carotid artery on PET-CT

Exclusion Criteria:

• Current medical history of auto-immune disease/vasculitis, active inflammatory diseases, Recent (<1 month prior to screening) or ongoing serious infection requiring IV antibiotic therapy.

• Recent or current treatment with medications that may have a significant effect on plaque inflammation as measured by plaque TBR, including but not limited to:

  • Steroids for at least 6 weeks prior to baseline measurement and during study (with the exception of inhaled acute use steroids).
  • Biological based medicines (anti-TNF (ex. Infliximab), anti-IL-6 therapy (ex. Tocilizumab) or anti-IL-1 (ex. anakinra)) within 8 weeks before the baseline visit and during the study
  • No other disease modifying antirheumatic drugs (DMRADS) within 6 weeks of baseline and during study (such as cyclosporine, azatioprine, etc.)
• Known systemic disorders such as hepatic, renal, hematologic, and malignant diseases or any clinically significant medical condition that could interfere with the conduct of the study.
• Changes in dose or frequency of doses at least 6 weeks prior to baseline measurement (unstable dosing) in angiotensin-converting enzyme (ACE) inhibitors (ACE-I) or angiotensin-receptor blockers (ARBs), non-statin lipid-modifying therapy, thiazolidinediones, inhaled steroids, or leukotriene modifying agents, nonsteroidal anti-inflammatory drugs (NSAIDS), and cyclo-oxygenase-2 inhibitors (COXIBs)
• Standard contra-indications to MRI, 18FDG PET, and CT based on physicians experience and current practices
• Current medical history of poorly controlled diabetes defined as hemoglobin A1c (HbA1c) >7.5%.
• Current medical history of drug or alcohol abuse within 12 months prior to screening.
• History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
• Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
• Subject has planned cardiac surgery, PCI or carotid stenting, or major non-cardiac surgery during the course of the study period or for 14 days after the last treatment.
• Use of any investigational drug in the 3 months prior to study drug administration.
• Use of insulin or any oral anti-diabetic (except metformin) in the 30 days prior to baseline measurements. Those subjects who are taking metformin may be included in the study if they are on a stable dose for at least 4 weeks and have a HbA1c <7.5%.
• Any contraindications for corticosteroid infusions (for example, but not limited current infections or vaccinations)