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

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ClinicalTrials.gov Identifier: NCT02272946
Recruitment Status : Recruiting
First Posted : October 23, 2014
Last Update Posted : March 9, 2020
Sponsor:
Information provided by (Responsible Party):
Priscilla Hsue, MD, University of California, San Francisco

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
HIV Cardiovascular Disease Drug: Canakinumab Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 2015
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Canakinumab

Arm Intervention/treatment
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 Name: IL--1β

Experimental: Canakinumab
In Stage II: About 67 subjects will receive 150mg Canakinumab subcutaneous injection.
Drug: Canakinumab
150mg Canakinumab received subcutaneously
Other Name: IL--1β

Placebo Comparator: Placebo
In Stage II: About 33 subjects will receive 150mg placebo subcutaneous injection
Drug: Placebo
150mg Placebo received subcutaneously




Primary Outcome Measures :
  1. Number of Adverse Events at week 1 as a measure of safety [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline, 12 weeks ]
    Assessed by FDG-PET/CT scanning

  3. Rate of change in inflammatory markers of CVD risk [ Time Frame: 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



Information from the National Library of Medicine

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02272946


Contacts
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Contact: Moore Kelvin 628-206-5145 kelvin.moorejr@ucsf.edu
Contact: Sohee Park 628-206-5801 rebecca.park2@ucsf.edu

Locations
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United States, California
San Francisco General Hospital Recruiting
San Francisco, California, United States, 94110
Contact: Kelvin Moore    628-206-5145    kelvin.moorejr@ucsf.edu   
Contact: Sohee Park, MS    628-206-5801    rebecca.park2@ucsf.edu   
Principal Investigator: Priscilla Hsue, MD         
Sponsors and Collaborators
Priscilla Hsue, MD
Investigators
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Principal Investigator: Priscilla Hsue, MD University of California, San Francisco

Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
The link above shows the current enrollment table of the Canakinumab study as of March 2, 2020. Of note, 40 participants have been enrolled in the study.
IL-1B inhibition [by way of Canakinumab] Reduces Atherosclerotic Inflammation in HIV Infection - Journal of the American College of Cardiology  This link exits the ClinicalTrials.gov site
The link above is the research publication written by Dr. Hsue (Primary Investigator) about how IL-1B inhibition [by way of Canakinumab] reduces atherosclerotic inflammation in the setting of HIV.

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Responsible Party: Priscilla Hsue, MD, Professor in Residence, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02272946    
Other Study ID Numbers: Canakinumab
First Posted: October 23, 2014    Key Record Dates
Last Update Posted: March 9, 2020
Last Verified: March 2020
Additional relevant MeSH terms:
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Inflammation
Cardiovascular Diseases
Pathologic Processes
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs