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

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

This trial will see if canakinumab, a drug that blocks IL‑1β, reduces artery inflammation in adults with prior heart attack or coronary stents, some of whom have TET2 clonal hematopoiesis.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (other)
• Drugs / interventions: radiation, canakinumab
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT06691217 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Adults aged 18 or older with prior heart attack or coronary stent placed more than 180 days before baseline imaging, who meet other safety criteria and either have TET2 CHIP or no CHIP variants on prior testing, are the intended participants.

Not a fit: People with recent drug‑eluting stents or coronary bypass surgery, active cancer, prior blood malignancy, organ/stem cell transplant, current systemic immunosuppression, pregnancy, or other excluded conditions are not eligible and are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could lower artery inflammation and potentially reduce future heart complications in people with coronary artery disease, especially those with TET2 CHIP.

How similar studies have performed: Previous large trials (for example CANTOS) showed that canakinumab can reduce cardiovascular events by lowering inflammation, but using TET2 CHIP status to guide therapy is a newer, less tested approach.

Eligibility criteria

Inclusion Criteria:

* 18 years or older
* Prior heart attack or coronary stent procedure \>180 days before baseline imaging
* Presence of either TET2 CHIP or no CHIP variants on prior sequencing

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 this trial is running

Boston, Massachusetts

• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)

Study contacts

• Study coordinator: Michael C Honigberg, MD MPP

Conditions: Vascular Inflammation, ASCVD, ASCVD Management, CHIP, TET2 CHIP, Clonal Hematopoiesis, ASCVD management