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

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ClinicalTrials.gov Identifier: NCT02272946
Recruitment Status : Active, not recruiting
First Posted : October 23, 2014
Last Update Posted : June 4, 2018
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

Study Description
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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

Study Design
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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 : September 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

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

Arms and Interventions
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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


Outcome Measures
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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


Eligibility Criteria
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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV infection,
  2. Age ≥ 40 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, diabetes medication (not including insulin) 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 or diabetes
  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. Requirement for insulin
  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
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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


Locations
United States, California
San Francisco General Hospital
San Francisco, California, United States, 94110
Quest Clinical Research
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Priscilla Hsue, MD University of California, San Francisco
More Information
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02272946     History of Changes
Other Study ID Numbers: Canakinumab
First Posted: October 23, 2014    Key Record Dates
Last Update Posted: June 4, 2018
Last Verified: May 2018

Additional relevant MeSH terms:
Inflammation
Cardiovascular Diseases
Pathologic Processes
 Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs