Blocking IL-1β to reduce artery inflammation in people with coronary artery disease, including those with TET2 clonal hematopoiesis

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a randomized, double‑blind, placebo‑controlled Phase 2 trial of canakinumab versus placebo in 120 adults with prior coronary artery disease, half of whom have TET2-driven clonal hematopoiesis. Participants are randomized 1:1 to receive injections at Weeks 0, 12, 24, and 36, with imaging at baseline and Week 48 and final safety follow-up at Week 60. The primary outcome is change in the fat attenuation index (FAI) on coronary CT angiography between baseline and Week 48, and a subset undergoes SPECT to measure macrophage-specific vascular inflammation. The trial also measures change in TET2 variant allele fraction in participants with TET2 CHIP.

Why it matters

Who can join: the full rules

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
* TET2-mutant myelodysplastic syndrome (MDS) or dysplastic-type chronic myelomonocytic leukemia (CMML) participants only must meet all of the following criteria:

  * Very low, low, or moderate-low risk for disease progression according to IPSS-M (score ≤0)
  * Peripheral blood blasts \<2% and bone marrow blasts \<5%
  * WBC \<13 ×10⁹/L
  * ANC ≥1.0 ×10⁹/L
  * Hemoglobin ≥10 g/dL
  * Platelet count ≥50 ×10⁹/L
  * No clinically significant transfusion requirement attributable to MDS/CMML, defined as receipt of \<2 units of RBCs and no platelet transfusions during the 8 weeks preceding screening (excluding transfusions for acute bleeding, surgery, or another transient intercurrent condition)
  * In the judgment of the treating oncologist, clinically stable disease for which disease-modifying therapy is not anticipated to be required within the subsequent 24 months

Exclusion Criteria:

* 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
* history of organ or stem cell transplantation
* current treatment with prescription, systemic (oral, IV \[intravenous\], or IM \[intramuscular\]) steroids or anti-inflammatory/immune suppressant medical therapies (including colchicine but excluding topical therapies, UV therapy, ASA-derivative therapies, or NSAIDS) for autoimmune/inflammatory diseases, post-transplant care, asthma, or pain
* use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for \>7 days within the past 1 month
* use of IV or IM steroids or IV or IM anti-inflammatory/immune suppressant medication within the past 3 months
* known allergy to dextran's and/or DTPA and/or radiometals and/or severe allergy to iodinated contrast media
* estimated glomerular filtration rate (eGFR) \< 45 ml/min/1.73 m2
* contraindications to nitroglycerin known narrow angle glaucoma, or known severe aortic stenosis
* use of phosphodiesterase type 5 inhibitor AND refusal to abstain from use of these medications within the 5 days prior to scheduled CCTA scan
* significant radiation exposure (40msV) received within the past 12 months
* concurrent enrollment in another research study judged by the investigators to interfere with the current study
* known active or recurrent hepatic disease (including cirrhosis or ALT/AST levels \>3 times the upper limit oof or total bilirubin \>2 times the upper limits of normal)
* history or evidence of tuberculosis (TB) (active or latent) infection or risk factor for TB
* active bacterial, fungal or viral infection at the time of enrollment or history of recurrent infections
* suspected or proven immunocompromised state
* live vaccinations within 3 months prior to randomization visit or live vaccinations planned during the trial

Where it's running

• Massachusetts General Hospital
  Boston, Massachusetts, United States Recruiting

Study contacts

• Study coordinator: Michael C Honigberg, MD MPP
• Email: mhonigberg@mgh.harvard.edu
• Phone: 617-726-1843

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.