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

June 16, 2026 updated by: Michael C. Honigberg, Massachusetts General Hospital
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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Michael C Honigberg, MD, MPP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
Time Frame: 48 weeks
48 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
Time Frame: 48 weeks
48 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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
Time Frame: 48 weeks
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
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
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
48 weeks
Predictors of the change in perivascular fat attenuation index (Hounsfield units) measured by coronary computed tomography angiography with canakinumab
Time Frame: 48 weeks
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
Time Frame: 48 weeks
48 weeks
Between-group difference (canakinumab versus placebo) in the change in inflammatory cytokines
Time Frame: 48 weeks
48 weeks
Between-group difference (canakinumab vs. placebo) in the change in bone marrow adipose tissue volume assessed using computed tomography
Time Frame: 48 weeks
48 weeks
Between-group difference (TET2 CHIP vs. no CHIP) in the perivascular fat attenuation index (Hounsfield units) measured by coronary computed tomography angiography
Time Frame: 0 weeks
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
Time Frame: 0 weeks
0 weeks
Between-group difference (TET2 CHIP vs. no CHIP) in the perivascular fat attenuation index (FAI) Score for all three major coronary arteries
Time Frame: 0 weeks
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
Time Frame: 0 weeks
0 weeks
Between-group difference (TET2 CHIP vs. no CHIP) in inflammatory cytokines
Time Frame: 0 weeks
0 weeks
Between-group difference (TET2 CHIP vs. no CHIP) in bone marrow adipose tissue volume assessed using computed tomography
Time Frame: 0 weeks
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
Time Frame: 48 weeks
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
Time Frame: 12 weeks (between Week 48 to Week 60)
12 weeks (between Week 48 to Week 60)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Massachusetts General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Yale University
National Institutes of Health (NIH)
Broad Institute of MIT and Harvard

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 24, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 14, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 15, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 18, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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