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

HIV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02272946
• Other study ID #: Canakinumab
• Status: Completed
• Phase: Phase 2
• Start date: September 2015
• Est. completion date: December 2021

Study information

• Verified date: March 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: December 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 59 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• HIV
• Inflammation

Intervention

Drug:
• Canakinumab
150mg Canakinumab received subcutaneously
• Placebo
150mg Placebo received subcutaneously

Locations

Country	Name	City	State
United States	San Francisco General Hospital	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Priscilla Hsue, MD	Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in CD4 Count From Baseline to Follow-up	Change in CD4 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.	weeks 4, 8, 12, 18, 24, and 36.
Primary	Change in CD8 Count From Baseline to Follow-up	Change in CD8 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.	weeks 4, 8, 12, 18, 24, and 36.
Primary	Change in Absolute Neutrophil Count From Baseline to Follow-up	Change in absolute neutrophil count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.	weeks 4, 8, 12, 18, 24, and 36.
Primary	Change in Platelet Count From Baseline to Follow-up	Change in platelet count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.	weeks 4, 8, 12, 18, 24, and 36.
Primary	Change in Creatinine Count From Baseline to Follow-up	Change in creatinine count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.	weeks 4, 8, 12, 18, 24, and 36.
Primary	Change in AST From Baseline to Follow-up	Change in AST from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.	weeks 4, 8, 12, 18, 24, and 36.
Primary	Change in ALT From Baseline to Follow-up	Change in ALT from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.	weeks 4, 8, 12, 18, 24, and 36.
Secondary	Flow-Mediated Dilation (FMD)	Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter	Baseline and Week 12
Secondary	Arterial Inflammation Measured at Baseline and Follow-up at Week 12	Change From Baseline in Arterial Fluorodeoxyglucose (FDG) Uptake Assessed by FDG-PET/CT and reported as target-to-background (TBR) ratio to measure of vascular inflammation	Baseline (entry) and Week 12
Secondary	D-Dimer	D-Dimer will be assessed from baseline to weeks 4, 8, 12, and 18.	Baseline, 4 weeks, 8 weeks, 12 weeks, and week 18
Secondary	Human Serum Amyloid A (SAA)	SAA will be assessed from baseline to weeks 4, 12, and 18.	Baseline, 4 weeks, 12 weeks, and week 18
Secondary	Tumor Necrosis Factor Alpha (TNFa)	TNFa will be assessed from baseline to weeks 4, 12, and 18.	Baseline, 4 weeks, 12 weeks, and week 18