Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
Condition: HIV; Cardiovascular Disease
MeSH terms: Cardiovascular Diseases; Inflammation
Intervention: Canakinumab; Placebo
Intervention description: 150mg Canakinumab received subcutaneously; 150mg Placebo received subcutaneously
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 43.0
Sex: All
Minimum age: 40 Years
Maximum age: 59 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the effects of IL-1β inhibition on safety, measures
      of systemic and vascular inflammation and endothelial function (all indicators of
      cardiovascular risk) in treated and suppressed HIV infected individuals This study will
      assess the safety and effects of canakinumab on endothelial function (assessed by
      flow-mediated vasodilation [FMD] of the brachial artery), vascular inflammation (assessed by
      FDG-PET/CT scanning), key inflammatory markers of cardiovascular disease (CVD) risk
      (high-sensitivity C-reactive protein [hsCRP]), interleukin-6 (IL-6), soluble CD163 (sCD163),
      D-dimer, T-cell and monocyte activation in the blood, and size of the HIV reservoir. 10
      individuals will receive a single dose of 150mg canakinumab with follow-up for 12 weeks. In
      the second part of the study, 100 participants will be randomized (2:1 - canakinumab to
      placebo) and will be followed by for 36 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          1. HIV infection,

          2. Age ≥ 40 years < 60 years

          3. On continuous ART for at least 12 months with no change in regimen in 12 weeks prior
             to study entry

          4. CD4+ T cell count ≥ 400 cells/mm3

          5. HIV RNA level below the standard limit of quantification for 52 weeks prior to entry

          6. High risk for CAD as defined by either documented CVD (including prior MI) or diabetes
             mellitus or 1 CVD risk factor (current smoking, hypertension, dyslipidemia, or
             hsCRP≥2mg/L.)

          7. Individuals on stable doses of lipid lowering therapy and/or anti-hypertensive
             medication will be allowed in the study.

          8. Appropriate documentation from medical records of prior receipt of pneumococcal
             vaccinations

        Exclusion Criteria:

          1. Women of childbearing potential or pregnant/nursing women

          2. CABG surgery in the past 3 years

          3. Class IV heart failure

          4. Uncontrolled HTN

          5. History of tuberculosis or latent TB that is not treated

          6. Nephrotic syndrome or eGFR< 30 ml/min/1.73m2

          7. Active hepatic disease or active/chronic hepatitis B or C

          8. Any prior malignancy including KS

          9. Serious illness requiring hospitalization or active infection requiring antibiotics
             within 90 days

         10. Requirement for live active vaccination 3 months prior to, during, and 3 months after
             study

         11. Concurrent immune modulating therapy

         12. Diabetes Mellitus

         13. History of multiple imaging studies associated with radiation exposure

         14. Neutropenia defined as ANC<1500/mm

         15. Triglycerides>400 mg/dL

         16. History of hypersensitivity to study drug

         17. History of EBV-related lymphoproliferative disorders

         18. Active or untreated latent TB infection