Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk

Priscilla Hsue, MD

Status and phase: Completed; Phase 2

Conditions: HIV; Cardiovascular Disease

Treatments: Drug: Canakinumab; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02272946

Canakinumab

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex: All

Ages: 40 to 59 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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43 participants in 3 patient groups, including a placebo group

Safety Arm

Other group

Description:

In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).

Treatment:

Drug: Canakinumab

Canakinumab

Experimental group

Description:

In Stage II: About 67 subjects will receive 150mg Canakinumab subcutaneous injection.

Treatment:

Drug: Canakinumab

Placebo

Placebo Comparator group

Description:

In Stage II: About 33 subjects will receive 150mg placebo subcutaneous injection

Treatment:

Drug: Placebo