The primary goal of this clinical trial is to test the hypothesis that the drug canakinumab (anti-IL-1B monoclonal antibody) decreases vascular inflammation when used by people with a history of coronary artery disease, including those with and without clonal hematopoiesis driven by mutations in TET2.
This is a prospective, randomized, double-blind, placebo-controlled study to test the effects of canakinumab, an inhibitor of interleukin-1B, on vascular inflammation in individuals with coronary artery disease. Half of the trial population will have clonal hematopoiesis of indeterminate potential (CHIP) driven by mutations in TET2. Participants (total N=120) will be randomized 1:1 to receive canakinumab (n=60) versus placebo (n=60). Baseline assessment in all participants will include coronary CT angiography, and a subset of participants in each group (n=16 per group) will undergo SPECT imaging to assess macrophage-specific vascular inflammation. After randomization, participants will have injection/safety visits at Week 0, Week 12, Week 24, and Week 36. Repeat imaging assessments for vascular inflammation will occur during the Week 48 visit(s). Participants will undergo final study and safety assessments at Week 60. The primary endpoint is change in the fat attenuation index (FAI) as measured by coronary CT angiography between baseline and Week 48. Other key endpoints are change in macrophage-specific inflammation by SPECT between baseline and Week 48 and change in TET2 clonal variant allele fraction among participant with TET2 clonal hematopoiesis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
120
Participants with and without TET2 CHIP will receive 150mg of canakinumab every 3 months for 4 doses as part of the randomized clinical trial part of this proposal.
Participants with and without TET2 CHIP will receive placebo injection every 3 months for 4 doses as part of the randomized clinical trial part of this proposal.
Massachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGBetween-group difference (canakinumab versus placebo) in the change in perivascular fat attenuation index (Hounsfield units) measured by coronary computed tomography angiography
Time frame: 48 weeks
Between-group difference (canakinumab versus placebo) in the percent change in TET2 variant allele fraction (proportion of mutated alleles in peripheral blood cells) ascertained by targeted genomic sequencing
Time frame: 48 weeks
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