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

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2016 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT02272946
First received: October 13, 2014
Last updated: July 31, 2016
Last verified: July 2016
  Purpose
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 Intervention Phase
HIV Cardiovascular Disease Drug: Canakinumab Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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:
  • 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

  • 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

  • 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


Estimated Enrollment: 110
Study Start Date: September 2015
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02272946

Contacts
Contact: Danny Li danny.li@ucsf.edu
Contact: Sophia Hur, MPH sophia.hur@ucsf.edu

Locations
United States, California
San Francisco General Hospital Recruiting
San Francisco, California, United States, 94110
Contact: Danny Li    415-206-5801    danny.li@ucsf.edu   
Contact: Sophia Hur, MPH    415-206-5145    sophia.hur@ucsf.edu   
Principal Investigator: Priscilla Hsue, MD         
Quest Clinical Research Recruiting
San Francisco, California, United States, 94115
Contact: Ula Kowalczyk    415-353-0212    ula@questclinical.com   
Contact: Shilpa Dutta    415-353-0212    shilpa@questclinical.com   
Principal Investigator: Jay Lalezari, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Priscilla Hsue, MD University of California, San Francisco
  More Information

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02272946     History of Changes
Other Study ID Numbers: Canakinumab
Study First Received: October 13, 2014
Last Updated: July 31, 2016

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

ClinicalTrials.gov processed this record on June 22, 2017