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

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

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
HIV; Cardiovascular Disease	Drug: Canakinumab; Drug: Placebo	Phase 2

Study Design

• 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

Arms and Interventions

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

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

• 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

Contacts and Locations

Contacts

Contact: Moore Kelvin; 628-206-5145; kelvin.moorejr@ucsf.edu

Contact: Sohee Park; 628-206-5801; rebecca.park2@ucsf.edu

Locations

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

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

More Information

Study Data/Documents: Clinical Study Report 

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 

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.

• 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
• Last Update Posted: March 9, 2020
• Last Verified: March 2020

Additional relevant MeSH terms:

Inflammation; Cardiovascular Diseases; Pathologic Processes