Cardiovascular Disease, HIV
Conditions
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. 10 individuals will receive a single dose of 150mg canakinumab with follow-up for 12 weeks. In the second part of the study, 100 participants will be randomized (2:1 - canakinumab to placebo) and will be followed by for 36 weeks.
Interventions
DRUGCanakinumab
150mg Canakinumab received subcutaneously
DRUGPlacebo
150mg Placebo received subcutaneously
Sponsors
Massachusetts General Hospital
Priscilla Hsue, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 59 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ALT From Baseline to Follow-up | weeks 4, 8, 12, 18, 24, and 36. | Change in ALT from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36. |
| Change in CD8 Count From Baseline to Follow-up | weeks 4, 8, 12, 18, 24, and 36. | Change in CD8 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36. |
| Change in Absolute Neutrophil Count From Baseline to Follow-up | weeks 4, 8, 12, 18, 24, and 36. | Change in absolute neutrophil count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36. |
| Change in Platelet Count From Baseline to Follow-up | weeks 4, 8, 12, 18, 24, and 36. | Change in platelet count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36. |
| Change in Creatinine Count From Baseline to Follow-up | weeks 4, 8, 12, 18, 24, and 36. | Change in creatinine count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36. |
| Change in AST From Baseline to Follow-up | weeks 4, 8, 12, 18, 24, and 36. | Change in AST from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36. |
| Change in CD4 Count From Baseline to Follow-up | weeks 4, 8, 12, 18, 24, and 36. | Change in CD4 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arterial Inflammation Measured at Baseline and Follow-up at Week 12 | Baseline (entry) and Week 12 | Change From Baseline in Arterial Fluorodeoxyglucose (FDG) Uptake Assessed by FDG-PET/CT and reported as target-to-background (TBR) ratio to measure of vascular inflammation |
| D-Dimer | Baseline, 4 weeks, 8 weeks, 12 weeks, and week 18 | D-Dimer will be assessed from baseline to weeks 4, 8, 12, and 18. |
| Human Serum Amyloid A (SAA) | Baseline, 4 weeks, 12 weeks, and week 18 | SAA will be assessed from baseline to weeks 4, 12, and 18. |
| Tumor Necrosis Factor Alpha (TNFa) | Baseline, 4 weeks, 12 weeks, and week 18 | TNFa will be assessed from baseline to weeks 4, 12, and 18. |
| Flow-Mediated Dilation (FMD) | Baseline and Week 12 | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
Canakinumab: 150mg Canakinumab received subcutaneously | 10 |
| Canakinumab In Stage II: 22 subjects will receive 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously | 25 |
| Placebo In Stage II: About 11 subjects will receive 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously | 8 |
| Total | 43 |
Baseline characteristics
| Characteristic | Safety Arm | Canakinumab | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 4 Participants | 1 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 21 Participants | 7 Participants | 37 Participants |
| Cardiovascular Disease | 3 Participants | 2 Participants | 1 Participants | 6 Participants |
| Diabetes | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
| Dyslipidemia on Statin Therapy | 8 Participants | 17 Participants | 4 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 25 Participants | 7 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hypertension | 9 Participants | 10 Participants | 2 Participants | 21 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 20 Participants | 7 Participants | 35 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 9 Participants | 23 Participants | 8 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 1 / 25 | 0 / 8 |
| other Total, other adverse events | 2 / 10 | 1 / 25 | 1 / 8 |
| serious Total, serious adverse events | 0 / 10 | 2 / 25 | 0 / 8 |
Outcome results
Primary
Change in Absolute Neutrophil Count From Baseline to Follow-up
Change in absolute neutrophil count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Time frame: weeks 4, 8, 12, 18, 24, and 36.
Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Safety Arm | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 8 | -0.137 log unit (k) per uL |
| Safety Arm | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 4 | -0.157 log unit (k) per uL |
| Safety Arm | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 12 | -0.065 log unit (k) per uL |
| Canakinumab | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 12 | -0.088 log unit (k) per uL |
| Canakinumab | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 4 | -0.149 log unit (k) per uL |
| Canakinumab | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 8 | -0.015 log unit (k) per uL |
| Canakinumab | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 18 | -0.110 log unit (k) per uL |
| Canakinumab | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 24 | -0.123 log unit (k) per uL |
| Canakinumab | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 36 | 0.056 log unit (k) per uL |
| Placebo | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 24 | 0.028 log unit (k) per uL |
| Placebo | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 18 | 0.053 log unit (k) per uL |
| Placebo | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 36 | 0.201 log unit (k) per uL |
| Placebo | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 8 | 0.044 log unit (k) per uL |
| Placebo | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 4 | -0.048 log unit (k) per uL |
| Placebo | Change in Absolute Neutrophil Count From Baseline to Follow-up | Week 12 | 0.046 log unit (k) per uL |
Primary
Change in ALT From Baseline to Follow-up
Change in ALT from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Time frame: weeks 4, 8, 12, 18, 24, and 36.
Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Safety Arm | Change in ALT From Baseline to Follow-up | Week 12 | 0.098 log ALT U/L |
| Safety Arm | Change in ALT From Baseline to Follow-up | Week 8 | -0.123 log ALT U/L |
| Safety Arm | Change in ALT From Baseline to Follow-up | Week 4 | 0.100 log ALT U/L |
| Canakinumab | Change in ALT From Baseline to Follow-up | Week 36 | 0.007 log ALT U/L |
| Canakinumab | Change in ALT From Baseline to Follow-up | Week 4 | 0.079 log ALT U/L |
| Canakinumab | Change in ALT From Baseline to Follow-up | Week 8 | 0.046 log ALT U/L |
| Canakinumab | Change in ALT From Baseline to Follow-up | Week 12 | 0.111 log ALT U/L |
| Canakinumab | Change in ALT From Baseline to Follow-up | Week 18 | 0.092 log ALT U/L |
| Canakinumab | Change in ALT From Baseline to Follow-up | Week 24 | 0.038 log ALT U/L |
| Placebo | Change in ALT From Baseline to Follow-up | Week 12 | 0.087 log ALT U/L |
| Placebo | Change in ALT From Baseline to Follow-up | Week 24 | 0.052 log ALT U/L |
| Placebo | Change in ALT From Baseline to Follow-up | Week 18 | 0.140 log ALT U/L |
| Placebo | Change in ALT From Baseline to Follow-up | Week 8 | 0.116 log ALT U/L |
| Placebo | Change in ALT From Baseline to Follow-up | Week 4 | -0.024 log ALT U/L |
| Placebo | Change in ALT From Baseline to Follow-up | Week 36 | 0.205 log ALT U/L |
Primary
Change in AST From Baseline to Follow-up
Change in AST from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Time frame: weeks 4, 8, 12, 18, 24, and 36.
Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Safety Arm | Change in AST From Baseline to Follow-up | Week 8 | -0.019 log AST U/L |
| Safety Arm | Change in AST From Baseline to Follow-up | Week 4 | 0.032 log AST U/L |
| Safety Arm | Change in AST From Baseline to Follow-up | Week 12 | 0.019 log AST U/L |
| Canakinumab | Change in AST From Baseline to Follow-up | Week 12 | 0.080 log AST U/L |
| Canakinumab | Change in AST From Baseline to Follow-up | Week 4 | 0.025 log AST U/L |
| Canakinumab | Change in AST From Baseline to Follow-up | Week 8 | 0.001 log AST U/L |
| Canakinumab | Change in AST From Baseline to Follow-up | Week 18 | 0.024 log AST U/L |
| Canakinumab | Change in AST From Baseline to Follow-up | Week 24 | 0.031 log AST U/L |
| Canakinumab | Change in AST From Baseline to Follow-up | Week 36 | 0.008 log AST U/L |
| Placebo | Change in AST From Baseline to Follow-up | Week 24 | -0.040 log AST U/L |
| Placebo | Change in AST From Baseline to Follow-up | Week 18 | 0.069 log AST U/L |
| Placebo | Change in AST From Baseline to Follow-up | Week 36 | 0.049 log AST U/L |
| Placebo | Change in AST From Baseline to Follow-up | Week 8 | 0.055 log AST U/L |
| Placebo | Change in AST From Baseline to Follow-up | Week 4 | -0.103 log AST U/L |
| Placebo | Change in AST From Baseline to Follow-up | Week 12 | 0.070 log AST U/L |
Primary
Change in CD4 Count From Baseline to Follow-up
Change in CD4 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Time frame: weeks 4, 8, 12, 18, 24, and 36.
Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Safety Arm | Change in CD4 Count From Baseline to Follow-up | Week 8 | -0.090 log cells per mm^3 |
| Safety Arm | Change in CD4 Count From Baseline to Follow-up | Week 4 | -0.085 log cells per mm^3 |
| Safety Arm | Change in CD4 Count From Baseline to Follow-up | Week 12 | -0.049 log cells per mm^3 |
| Canakinumab | Change in CD4 Count From Baseline to Follow-up | Week 12 | -0.111 log cells per mm^3 |
| Canakinumab | Change in CD4 Count From Baseline to Follow-up | Week 4 | -0.024 log cells per mm^3 |
| Canakinumab | Change in CD4 Count From Baseline to Follow-up | Week 8 | 0.004 log cells per mm^3 |
| Canakinumab | Change in CD4 Count From Baseline to Follow-up | Week 18 | -0.105 log cells per mm^3 |
| Canakinumab | Change in CD4 Count From Baseline to Follow-up | Week 24 | -0.142 log cells per mm^3 |
| Canakinumab | Change in CD4 Count From Baseline to Follow-up | Week 36 | -0.109 log cells per mm^3 |
| Placebo | Change in CD4 Count From Baseline to Follow-up | Week 24 | -0.012 log cells per mm^3 |
| Placebo | Change in CD4 Count From Baseline to Follow-up | Week 18 | -0.009 log cells per mm^3 |
| Placebo | Change in CD4 Count From Baseline to Follow-up | Week 36 | -0.164 log cells per mm^3 |
| Placebo | Change in CD4 Count From Baseline to Follow-up | Week 8 | -0.015 log cells per mm^3 |
| Placebo | Change in CD4 Count From Baseline to Follow-up | Week 4 | -0.020 log cells per mm^3 |
| Placebo | Change in CD4 Count From Baseline to Follow-up | Week 12 | -0.070 log cells per mm^3 |
Primary
Change in CD8 Count From Baseline to Follow-up
Change in CD8 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Time frame: weeks 4, 8, 12, 18, 24, and 36.
Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Safety Arm | Change in CD8 Count From Baseline to Follow-up | Week 8 | -0.103 log cells per mm^3 |
| Safety Arm | Change in CD8 Count From Baseline to Follow-up | Week 4 | -0.101 log cells per mm^3 |
| Safety Arm | Change in CD8 Count From Baseline to Follow-up | Week 12 | -0.166 log cells per mm^3 |
| Canakinumab | Change in CD8 Count From Baseline to Follow-up | Week 12 | -0.192 log cells per mm^3 |
| Canakinumab | Change in CD8 Count From Baseline to Follow-up | Week 4 | -0.039 log cells per mm^3 |
| Canakinumab | Change in CD8 Count From Baseline to Follow-up | Week 8 | -0.069 log cells per mm^3 |
| Canakinumab | Change in CD8 Count From Baseline to Follow-up | Week 18 | -0.202 log cells per mm^3 |
| Canakinumab | Change in CD8 Count From Baseline to Follow-up | Week 24 | -0.159 log cells per mm^3 |
| Canakinumab | Change in CD8 Count From Baseline to Follow-up | Week 36 | -0.171 log cells per mm^3 |
| Placebo | Change in CD8 Count From Baseline to Follow-up | Week 24 | -0.020 log cells per mm^3 |
| Placebo | Change in CD8 Count From Baseline to Follow-up | Week 18 | -0.098 log cells per mm^3 |
| Placebo | Change in CD8 Count From Baseline to Follow-up | Week 36 | -0.198 log cells per mm^3 |
| Placebo | Change in CD8 Count From Baseline to Follow-up | Week 8 | -0.040 log cells per mm^3 |
| Placebo | Change in CD8 Count From Baseline to Follow-up | Week 4 | 0.006 log cells per mm^3 |
| Placebo | Change in CD8 Count From Baseline to Follow-up | Week 12 | -0.111 log cells per mm^3 |
Primary
Change in Creatinine Count From Baseline to Follow-up
Change in creatinine count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Time frame: weeks 4, 8, 12, 18, 24, and 36.
Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Safety Arm | Change in Creatinine Count From Baseline to Follow-up | Week 8 | -0.001 log mg/dL |
| Safety Arm | Change in Creatinine Count From Baseline to Follow-up | Week 4 | -0.017 log mg/dL |
| Safety Arm | Change in Creatinine Count From Baseline to Follow-up | Week 12 | -0.001 log mg/dL |
| Canakinumab | Change in Creatinine Count From Baseline to Follow-up | Week 12 | -0.030 log mg/dL |
| Canakinumab | Change in Creatinine Count From Baseline to Follow-up | Week 4 | 0.032 log mg/dL |
| Canakinumab | Change in Creatinine Count From Baseline to Follow-up | Week 8 | 0.014 log mg/dL |
| Canakinumab | Change in Creatinine Count From Baseline to Follow-up | Week 18 | -0.017 log mg/dL |
| Canakinumab | Change in Creatinine Count From Baseline to Follow-up | Week 24 | -0.004 log mg/dL |
| Canakinumab | Change in Creatinine Count From Baseline to Follow-up | Week 36 | 0.014 log mg/dL |
| Placebo | Change in Creatinine Count From Baseline to Follow-up | Week 24 | -0.008 log mg/dL |
| Placebo | Change in Creatinine Count From Baseline to Follow-up | Week 18 | -0.068 log mg/dL |
| Placebo | Change in Creatinine Count From Baseline to Follow-up | Week 36 | -0.037 log mg/dL |
| Placebo | Change in Creatinine Count From Baseline to Follow-up | Week 8 | -0.012 log mg/dL |
| Placebo | Change in Creatinine Count From Baseline to Follow-up | Week 4 | -0.011 log mg/dL |
| Placebo | Change in Creatinine Count From Baseline to Follow-up | Week 12 | -0.037 log mg/dL |
Primary
Change in Platelet Count From Baseline to Follow-up
Change in platelet count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Time frame: weeks 4, 8, 12, 18, 24, and 36.
Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Safety Arm | Change in Platelet Count From Baseline to Follow-up | Week 8 | -0.029 log unit (k) per uL |
| Safety Arm | Change in Platelet Count From Baseline to Follow-up | Week 4 | -0.098 log unit (k) per uL |
| Safety Arm | Change in Platelet Count From Baseline to Follow-up | Week 12 | -0.014 log unit (k) per uL |
| Canakinumab | Change in Platelet Count From Baseline to Follow-up | Week 12 | -0.020 log unit (k) per uL |
| Canakinumab | Change in Platelet Count From Baseline to Follow-up | Week 4 | -0.079 log unit (k) per uL |
| Canakinumab | Change in Platelet Count From Baseline to Follow-up | Week 8 | -0.032 log unit (k) per uL |
| Canakinumab | Change in Platelet Count From Baseline to Follow-up | Week 18 | 0.015 log unit (k) per uL |
| Canakinumab | Change in Platelet Count From Baseline to Follow-up | Week 24 | 0.016 log unit (k) per uL |
| Canakinumab | Change in Platelet Count From Baseline to Follow-up | Week 36 | 0.045 log unit (k) per uL |
| Placebo | Change in Platelet Count From Baseline to Follow-up | Week 24 | 0.054 log unit (k) per uL |
| Placebo | Change in Platelet Count From Baseline to Follow-up | Week 18 | 0.028 log unit (k) per uL |
| Placebo | Change in Platelet Count From Baseline to Follow-up | Week 36 | -0.016 log unit (k) per uL |
| Placebo | Change in Platelet Count From Baseline to Follow-up | Week 8 | 0.007 log unit (k) per uL |
| Placebo | Change in Platelet Count From Baseline to Follow-up | Week 4 | 0.026 log unit (k) per uL |
| Placebo | Change in Platelet Count From Baseline to Follow-up | Week 12 | 0.014 log unit (k) per uL |
Secondary
Arterial Inflammation Measured at Baseline and Follow-up at Week 12
Change From Baseline in Arterial Fluorodeoxyglucose (FDG) Uptake Assessed by FDG-PET/CT and reported as target-to-background (TBR) ratio to measure of vascular inflammation
Time frame: Baseline (entry) and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Safety Arm | Arterial Inflammation Measured at Baseline and Follow-up at Week 12 | Baseline (Entry) | 3.27 target-to-background ratio | Standard Deviation 0.57 |
| Safety Arm | Arterial Inflammation Measured at Baseline and Follow-up at Week 12 | Week 12 | 2.97 target-to-background ratio | Standard Deviation 0.64 |
| Canakinumab | Arterial Inflammation Measured at Baseline and Follow-up at Week 12 | Baseline (Entry) | 3.18 target-to-background ratio | Standard Deviation 0.58 |
| Canakinumab | Arterial Inflammation Measured at Baseline and Follow-up at Week 12 | Week 12 | 3.21 target-to-background ratio | Standard Deviation 0.73 |
| Placebo | Arterial Inflammation Measured at Baseline and Follow-up at Week 12 | Baseline (Entry) | 3.85 target-to-background ratio | Standard Deviation 1.14 |
| Placebo | Arterial Inflammation Measured at Baseline and Follow-up at Week 12 | Week 12 | 4.01 target-to-background ratio | Standard Deviation 0.78 |
Secondary
D-Dimer
D-Dimer will be assessed from baseline to weeks 4, 8, 12, and 18.
Time frame: Baseline, 4 weeks, 8 weeks, 12 weeks, and week 18
Population: The safety arm is an open label study with D-Dimer markers evaluated at baseline, week 4, and week 8.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Safety Arm | D-Dimer | Baseline | 548.3 ng/mL |
| Safety Arm | D-Dimer | Week 4 | 499.7 ng/mL |
| Safety Arm | D-Dimer | Week 8 | 562.4 ng/mL |
| Canakinumab | D-Dimer | Week 12 | 2126.05 ng/mL |
| Canakinumab | D-Dimer | Week 4 | 2042.96 ng/mL |
| Canakinumab | D-Dimer | Baseline | 2121.89 ng/mL |
| Canakinumab | D-Dimer | Week 18 | 1879.56 ng/mL |
| Placebo | D-Dimer | Week 18 | 1669.79 ng/mL |
| Placebo | D-Dimer | Baseline | 1917.03 ng/mL |
| Placebo | D-Dimer | Week 4 | 2080.01 ng/mL |
| Placebo | D-Dimer | Week 12 | 1894.52 ng/mL |
Secondary
Flow-Mediated Dilation (FMD)
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
Time frame: Baseline and Week 12
Population: The safety arm is an open label study where brachial artery FMD was measured at baseline and week 8.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Safety Arm | Flow-Mediated Dilation (FMD) | Baseline FMD at 45 Seconds | 3 Percent change in artery diameter |
| Safety Arm | Flow-Mediated Dilation (FMD) | Baseline FMD at 60 Seconds | 4 Percent change in artery diameter |
| Safety Arm | Flow-Mediated Dilation (FMD) | Baseline FMD at 75 Seconds | 4 Percent change in artery diameter |
| Safety Arm | Flow-Mediated Dilation (FMD) | Baseline FMD at 90 Seconds | 2 Percent change in artery diameter |
| Safety Arm | Flow-Mediated Dilation (FMD) | Week 8 FMD at 45 Seconds | 3 Percent change in artery diameter |
| Safety Arm | Flow-Mediated Dilation (FMD) | Week 8 FMD at 60 Seconds | 3 Percent change in artery diameter |
| Safety Arm | Flow-Mediated Dilation (FMD) | Week 8 FMD at 75 Seconds | 3 Percent change in artery diameter |
| Safety Arm | Flow-Mediated Dilation (FMD) | Week 8 FMD at 90 Seconds | 2 Percent change in artery diameter |
| Canakinumab | Flow-Mediated Dilation (FMD) | Baseline FMD at 75 Seconds | 3 Percent change in artery diameter |
| Canakinumab | Flow-Mediated Dilation (FMD) | Baseline FMD at 90 Seconds | 3 Percent change in artery diameter |
| Canakinumab | Flow-Mediated Dilation (FMD) | Week 12 FMD at 45 Seconds | 3 Percent change in artery diameter |
| Canakinumab | Flow-Mediated Dilation (FMD) | Week 12 FMD at 60 Seconds | 3 Percent change in artery diameter |
| Canakinumab | Flow-Mediated Dilation (FMD) | Week 12 FMD at 75 Seconds | 2 Percent change in artery diameter |
| Canakinumab | Flow-Mediated Dilation (FMD) | Baseline FMD at 45 Seconds | 3 Percent change in artery diameter |
| Canakinumab | Flow-Mediated Dilation (FMD) | Baseline FMD at 60 Seconds | 4 Percent change in artery diameter |
| Canakinumab | Flow-Mediated Dilation (FMD) | Week 12 FMD at 90 Seconds | 2 Percent change in artery diameter |
| Placebo | Flow-Mediated Dilation (FMD) | Baseline FMD at 75 Seconds | 3 Percent change in artery diameter |
| Placebo | Flow-Mediated Dilation (FMD) | Week 12 FMD at 90 Seconds | 3 Percent change in artery diameter |
| Placebo | Flow-Mediated Dilation (FMD) | Baseline FMD at 60 Seconds | 4 Percent change in artery diameter |
| Placebo | Flow-Mediated Dilation (FMD) | Baseline FMD at 90 Seconds | 2 Percent change in artery diameter |
| Placebo | Flow-Mediated Dilation (FMD) | Baseline FMD at 45 Seconds | 3 Percent change in artery diameter |
| Placebo | Flow-Mediated Dilation (FMD) | Week 12 FMD at 45 Seconds | 4 Percent change in artery diameter |
| Placebo | Flow-Mediated Dilation (FMD) | Week 12 FMD at 75 Seconds | 4 Percent change in artery diameter |
| Placebo | Flow-Mediated Dilation (FMD) | Week 12 FMD at 60 Seconds | 4 Percent change in artery diameter |
Secondary
Human Serum Amyloid A (SAA)
SAA will be assessed from baseline to weeks 4, 12, and 18.
Time frame: Baseline, 4 weeks, 12 weeks, and week 18
Population: The safety arm did not evaluate Human Serum Amyloid A
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Canakinumab | Human Serum Amyloid A (SAA) | Baseline | 479058.3 pg/mL |
| Canakinumab | Human Serum Amyloid A (SAA) | Week 12 | 844889.8 pg/mL |
| Canakinumab | Human Serum Amyloid A (SAA) | Week 4 | 310588.7 pg/mL |
| Canakinumab | Human Serum Amyloid A (SAA) | Week 18 | 8838641 pg/mL |
| Placebo | Human Serum Amyloid A (SAA) | Week 4 | 20045206 pg/mL |
| Placebo | Human Serum Amyloid A (SAA) | Baseline | 513209.75 pg/mL |
| Placebo | Human Serum Amyloid A (SAA) | Week 18 | 615594.95 pg/mL |
| Placebo | Human Serum Amyloid A (SAA) | Week 12 | 1968440.05 pg/mL |
Secondary
Tumor Necrosis Factor Alpha (TNFa)
TNFa will be assessed from baseline to weeks 4, 12, and 18.
Time frame: Baseline, 4 weeks, 12 weeks, and week 18
Population: The safety arm did not evaluate Tumor Necrosis Factor Alpha
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Canakinumab | Tumor Necrosis Factor Alpha (TNFa) | Baseline | 1.69 pg/mL |
| Canakinumab | Tumor Necrosis Factor Alpha (TNFa) | Week 4 | 1.47 pg/mL |
| Canakinumab | Tumor Necrosis Factor Alpha (TNFa) | Week 12 | 1.18 pg/mL |
| Canakinumab | Tumor Necrosis Factor Alpha (TNFa) | Week 18 | 1.16 pg/mL |
| Placebo | Tumor Necrosis Factor Alpha (TNFa) | Week 18 | 1.41 pg/mL |
| Placebo | Tumor Necrosis Factor Alpha (TNFa) | Baseline | 1.24 pg/mL |
| Placebo | Tumor Necrosis Factor Alpha (TNFa) | Week 12 | 1.4 pg/mL |
| Placebo | Tumor Necrosis Factor Alpha (TNFa) | Week 4 | 1.34 pg/mL |