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

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.

Study Overview

• Status: Recruiting
• Conditions: Vascular Inflammation; ASCVD; ASCVD Management
• Intervention / Treatment: Drug: Saline (NaCl 0,9 %) (placebo); Drug: CANAKINUMAB (ILARIS®)

Detailed 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 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
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael C Honigberg, MD MPP; Phone Number: 617-726-1843; Email: mhonigberg@mgh.harvard.edu
• Study Contact Backup: Name: Mabel Toribio, MD; Phone Number: (617)-724-2826; Email: mptoribio@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Victoria R Viscosi, MS; Phone Number: 617-724-2996; Email: vviscosi@mgh.harvard.edu
      • Contact: Jack H.A. Miller, BS; Phone Number: 617-643-7546; Email: jmiller90@mgh.harvard.edu
      • Principal Investigator: Michael C Honigberg, MD, MPP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo: Control; 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.	Drug: Saline (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.
Experimental: Treatment: Canakinumab; 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.	Drug: CANAKINUMAB (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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Between-group difference (canakinumab versus placebo) in the change in perivascular fat attenuation index (Hounsfield units) measured by coronary computed tomography angiography	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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	48 weeks

Other Outcome Measures

Outcome Measure	Time Frame
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	48 weeks
Between-group difference (canakinumab versus placebo) in the fatty attenuation index (FAI) Score in all 3 major coronary arteries	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	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	48 weeks
Predictors of the change in perivascular fat attenuation index (Hounsfield units) measured by coronary computed tomography angiography with canakinumab	48 weeks
Between-group difference (canakinumab vs. placebo) in the change in aortic volume with 99mTc-tilmanocept uptake (percent of aortic volume) measured by single-photon emission computed tomography	48 weeks
Between-group difference (canakinumab versus placebo) in the change in inflammatory cytokines	48 weeks
Between-group difference (canakinumab vs. placebo) in the change in bone marrow adipose tissue volume assessed using computed tomography	48 weeks
Between-group difference (TET2 CHIP vs. no CHIP) in the perivascular fat attenuation index (Hounsfield units) measured by coronary computed tomography angiography	0 weeks
Between-group difference (TET2 CHIP vs. no CHIP) in the fatty attenuation index in the vessel with the highest fatty attenuation index (measured by coronary computed tomography angiography) in each participant	0 weeks
Between-group difference (TET2 CHIP vs. no CHIP) in the perivascular fat attenuation index (FAI) Score for all three major coronary arteries	0 weeks
Between-group difference (TET2 CHIP vs. no CHIP) in aortic volume with 99mTc-tilmanocept uptake (percent of aortic volume) measured by single-photon emission computed tomography	0 weeks
Between-group difference (TET2 CHIP vs. no CHIP) in inflammatory cytokines	0 weeks
Between-group difference (TET2 CHIP vs. no CHIP) in bone marrow adipose tissue volume assessed using computed tomography	0 weeks
Between-group difference (canakinumab versus placebo) in the percent change in variant allele fraction (proportion of mutated alleles in peripheral blood cells) ascertained by targeted genomic sequencing for non-TET2 CHIP clones	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	12 weeks (between Week 48 to Week 60)

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Yale University; National Institutes of Health (NIH); Broad Institute of MIT and Harvard

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Vascular Inflammation; ASCVD; Clonal Hematopoiesis; CHIP; TET2 CHIP; ASCVD management
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; canakinumab; Sodium Chloride
• Other Study ID Numbers: 2024P002825

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared outside of MGH. All samples and images being analyzed by outside vendors will be de-identified

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes