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

Sponsor
Priscilla Hsue, MD (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02272946
Collaborator
(none)
110
1
3
87
1.3

Study Details

Study Description

Brief 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. 20 individuals will receive a single dose of 150mg canakinumab with follow-up for 18 weeks.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
110 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
Study Start Date :
Sep 1, 2015
Actual Primary Completion Date :
Feb 1, 2021
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Other: Safety Arm

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

Drug: Canakinumab
150mg Canakinumab received subcutaneously
Other Names:
  • IL--1β
  • Experimental: Canakinumab

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

    Drug: Canakinumab
    150mg Canakinumab received subcutaneously
    Other Names:
  • IL--1β
  • Placebo Comparator: Placebo

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

    Drug: Placebo
    150mg Placebo received subcutaneously

    Outcome Measures

    Primary Outcome Measures

    1. Number of Adverse Events at week 1 as a measure of safety [Week 1]

      Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose

    2. Number of Adverse Events at week 2 as a measure of safety [Week 2]

      Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose

    3. Number of Adverse Events at week 4 as a measure of safety [Week 4]

      Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose, CD4 count, HIV-1 RNA

    4. Number of Adverse Events at week 8 as a measure of safety [Week 8]

      Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose, CD4 count, HIV-1 RNA

    5. Number of Adverse Events at week 12 as a measure of safety [Week 12]

      Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose, CD4 count, HIV-1 RNA

    6. Number of Adverse Events at week 18 as a measure of safety [Week 18]

      Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose

    7. Number of Adverse Events at baseline as a measure of safety [Baseline]

      Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose

    Secondary Outcome Measures

    1. Change in brachial artery flow-mediated vasodilation (FMD) [Baseline, 12 weeks]

      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

    2. Change From Baseline in Arterial Fluorodeoxyglucose (FDG) Uptake Assessed by FDG-PET/CT as a measure of vascular inflammation [Baseline, 12 weeks]

      Assessed by FDG-PET/CT scanning

    3. Rate of change in inflammatory markers of CVD risk [Baseline, 4 weeks, 12 weeks, 18 weeks]

      Linear mixed modelling will be used to estimate rates of change over the 18 weeks of treatment. Inflammatory markers: 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years to 59 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 San Francisco General Hospital San Francisco California United States 94110

    Sponsors and Collaborators

    • Priscilla Hsue, MD

    Investigators

    • Principal Investigator: Priscilla Hsue, MD, University of California, San Francisco

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Priscilla Hsue, MD, Professor in Residence, University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT02272946
    Other Study ID Numbers:
    • Canakinumab
    First Posted:
    Oct 23, 2014
    Last Update Posted:
    Nov 10, 2021
    Last Verified:
    Nov 1, 2021
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 10, 2021