Effects of IL-1 Beta Inhibition on Vascular Inflammation in TET2 Clonal Hematopoiesis
Massachusetts General Hospital
Summary
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.
Description
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 imagi…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 18 years or older * Coronary artery disease, defined as prior heart attack, coronary stent procedure \>180 days before baseline imaging, or advanced subclinical coronary atherosclerosis (coronary artery calcium score ≥300 Agatston units, CAD-RADS 3 or greater atherosclerosis on coronary CT angiography, or qualitatively severe coronary artery calcification identified on non-gated CT imaging) * Presence of either TET2 mutations or no myeloid driver mutations on prior sequencing Exclusion Criteria: * placement of a drug-eluting stent in a proximal coronary arterial segmen…
Interventions
- DrugCANAKINUMAB (ILARIS®)
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.
- DrugSaline (NaCl 0,9 %) (placebo)
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.
Location
- Massachusetts General HospitalBoston, Massachusetts