Effects of IL-1 Beta Inhibition on Vascular Inflammation in TET2 Clonal Hematopoiesis

ConditionsVascular Inflammation ASCVD ASCVD Management

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorMassachusetts General Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

placement of a drug-eluting stent in a proximal coronary arterial segment <180 days before baseline imaging

prior coronary artery bypass grafting

pregnancy or breastfeeding

history of blood malignancy or current solid-tumor malignancy

Trial design

Design model

Parallel

Treatments tested in this trial

CANAKINUMAB (ILARIS®)
Drug
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.
Saline (NaCl 0,9 %) (placebo)
Drug
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.

Treatment groups

120 Participants

are divided into 2 treatment groups

Group A: Placebo: ControlPlacebo comparator 1 intervention

Group B: Treatment: CanakinumabExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Between-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

Secondary outcomes

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

Other outcomes

Between-group difference (canakinumab vs. placebo) in the change in the fatty attenuation index in the vessel with the highest fatty attenuation index (measured by coronary computed tomography angiography) in each participant

Time frame

48 weeks

Between-group difference (canakinumab versus placebo) in the fatty attenuation index (FAI) Score in all 3 major coronary arteries

Time frame

48 weeks

Between-group differences in effect of canakinumab on perivascular fatty attenuation index (measured using coronary computed tomography angiography) between those with TET2 CHIP vs. no CHIP using pooled placebo groups

Time frame

48 weeks

TET2 CHIP-specific effect on the between-group difference in change with canakinumab in perivascular fat attenuation index (Hounsfield units) measured by coronary computed tomography angiography

Time frame

48 weeks