Cardiac SarcoidosisPhase 2MAGiC-ARTNCT04017936
Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis
A Phase 2 study testing Anakinra in people with Cardiac Sarcoidosis, run by Virginia Commonwealth University at 2 sites in United States.
Trial summary
Sarcoidosis is a heterogeneous disorder of unknown etiology whose signature lesions are granulomatous inflammatory infiltrates in involved tissues. Tissue commonly affected are lungs, skin, eyes, lymph nodes and the heart. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Cardiac Sarcoidosis
- What is being tested?
- Anakinra
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Oct 2020to 30 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society or the New Japanese Cardiac Sarcoidosis Guidelines (must meet one of the diagnostic pathways)
- Heart Rhythm Society Diagnostic Criteria based on 2 diagnostic pathways:
- Histological diagnosis from myocardial tissue - cardiac sarcoidosis is diagnosed in the presence of non-caseating granuloma on histologic examination of myocardial tissue with no alternative cause identified (including negative stain for microorganisms - as applicable);
- Clinical diagnosis from invasive and/or non-invasive studies - it is probable that there is cardiac sarcoidosis if there is (a) histological diagnosis of extracardiac sarcoidosis and (b) one or more of the following: steroid +/- immunosuppressant responsive cardiomyopathy or heart block; unexplained reduction in LVEF (<40%); unexplained sustained (spontaneous or induced) ventricular tachycardia; Mobitz type II 2nd degree or 3rd degree AV block; patchy uptake on dedicated cardiac PET (in a pattern consistent with cardiac sarcoidosis); late gadolinium enhancement on cardiac magnetic resonance (in a pattern consistent with cardiac sarcoidosis); positive gallium uptake (in a pattern consistent with cardiac sarcoidosis) and (c) other causes for the cardiac manifestation(s) have been reasonable excluded.
- Japanese Cardiac Sarcoidosis Diagnostic Criteria:
- Histological diagnosis group (those with positive myocardial biopsy findings) Cardiac sarcoidosis is diagnosed histologically when endomyocardial biopsy or surgical specimens demonstrate non-caseating epithelioid granulomas.
Show all 49Show fewer
- Clinical diagnosis group (those with negative myocardial biopsy findings or those not undergoing myocardial biopsy)
- The patient is clinically diagnosed as having sarcoidosis:
- When epithelioid granulomas are found in organs other than the heart and clinical findings strongly suggestive of the above-mentioned cardiac involvement are present (Table 1); or
- When the patient shows clinical findings strongly suggestive of pulmonary or ophthalmic sarcoidosis; at least 2 of the 5 characteristic laboratory findings of a sarcoidosis (Table 2); and clinical findings strongly suggest the above-mentioned cardiac involvement (Table 1)
- TABLE 1. Clinical findings defining cardiac involvement Cardiac findings should be assess based on the major criteria and the minor criteria. Clinical findings that satisfy the following 1) or 2) strongly suggest the presence of cardiac involvement.
- 2 or more of the 5 major criteria (a)-(e) are satisfied.
- 1 of the 5 major criteria (a)-(e) and 2 or more of the 3 minor criteria (f)-(h) are satisfied.
- 1. Major criteria
- High-grade AV block (including complete AV block) or fatal ventricular arrhythmia (e.g., sustained VT and VF)
- Basal thinning of the ventricular septum or abnormal ventricular wall anatomy (ventricular aneurysm, thinning of the middle or upper ventricular septum, regional wall thickening
- Left ventricular contractile dysfunction (LVEF < 50%)
- 67Ga citrate scintigraphy or 18F-FDG PET reveals abnormally high tracer accumulation in the heart
- Gadolinium-enhanced MRI revealed delayed contrast enhancement of the myocardium 2. Minor criteria
- Abnormal ECG findings: Ventricular arrhythmias (nonsustained VT, multifocal or frequent premature ventricular contractions, bundle branch block, axis deviation, or abnormal Q waves
- Perfusion defects on myocardial perfusion scintigraphy (SPECT)
- Endomyocardial biopsy: Monocyte infiltration and moderate or severe myocardial interstitial fibrosis
- Table 2. Characteristic laboratory findings of sarcoidosis 6. Bilateral hilar lymphadenopathy 7. High serum angiotensin-converting (ACE) activity or elevated serum lysozyme levels 8. High serum soluble interleukin-2 receptor (sIL-2R) levels 9. Significant tracer accumulation in 67Ga citrate scintigraphy or 18F-FDG PET 10. A high percentage of lymphocytes with a CD4CD8 ration of >3.5 in BAL fluid. 11.
- Diagnostic guidelines for isolated cardiac sarcoidosis based on New CS Guidelines in Japan Prerequisite
- No clinical findings characteristic of sarcoidosis are observed in any organs other than the heart. (The patient should be examined in detail for respiratory, ophthalmic, and skin involvement of sarcoidosis. When the patient is symptomatic, other etiologies that can affect the corresponding organs must be ruled out.)
- 67Ga scintigraphy or 18F-FDG PET reveals no abnormal tracer accumulation in any organs other than the heart.
- A chest CT scan reveals no shadow along the lymphatic tracts in the lungs or no hilar and mediastinal lymphadenopathy (minor axis>10 mm).
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- Histological diagnosis group Isolated cardiac sarcoidosis is diagnosed histologically when endomyocardial biopsy or surgical specimens demonstrate non-caseating epithelioid granulomas.
- Clinical diagnosis group Isolated cardiac sarcoidosis is diagnosed clinically when criterion (d) and at least 3 other major criteria (a)-(e) are satisfied. (Table 1)
- Cardiac fluoro-deoxyglucose uptake on recent PET (performed within the prior month).
- CRP high-sensitivty assay >2 mg/l.
- EXCLUSION CRITERIA (any of the following criteria would result in exclusion)
- Age<21 years;
- Pregnancy;
- Inability to obtain consent from patient or legally authorized representative;
- Contraindications to treatment with Anakinra (Kineret)(i.e. prior allergic reaction to the drug or to E. coli derived products or severe allergy to latex);
- Severe anemia (Hgb<8 g/dl - due to the need of more frequent blood sampling with this study).
- Acute or chronic active infections (not including treated/cured HCV with negative viral load).
- Acute or chronic inflammatory disease or immunosuppressive therapies (excluding stable [>1 month] oral corticosteroids at a dose of prednisone less than 0.5 mg/kg/day or methotrexate).
- Active acute or chronic psychiatric illness that in the opinion of the investigator may prevent from complying with study instructions;
- Limited English Proficiency that in the opinion of the investigator may prevent from understanding the content of the informed consent form or safely completing the study procedures.
- Live vaccination within the prior month
- Neutropenia (defined as absolute neutrophil count < 1,500/ml or <1,000/ml if subject is African American)
- History of malignancy within the prior 5 years (with exception of basal cell skin cancer, carcinoma in-situ of the cervix or low risk prostate cancer after curative therapy)
- Participation in another concurrent intervention study within 30 day or treatment with an investigational drug within 5 half-lives prior to randomization
- Severe kidney disease (GFR <30 mL/min/1.73m2)
- Evidence of COVID-19 within the last 60 days or recent (21 days) exposure to close personal contact with COVID-19.
- [Chronic, moderate-to-severe kidney disease (GFR <60 mL/min/1.73m2) or acute kidney injury, or history of severe hypersensitivity reactions to gadolinium-based contrast agents] - For VCU Imaging Substudy
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Michigan Sarcoidosis Clinic
Ann Arbor, Michigan, 48109
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
Sarcoidosis is a heterogeneous disorder of unknown etiology whose signature lesions are granulomatous inflammatory infiltrates in involved tissues. Tissue commonly affected are lungs, skin, eyes, lymph nodes and the heart. In this latter case, cardiac sarcoidosis (CS) can lead to atrioventricular (AV) blocks, ventricular arrhythmias, heart failure (HF) and sudden cardiac death. Similar to other involved organs, cardiac disease generally progresses from areas of focal inflammation to scar. However, the natural history of CS is not well characterized complicating an immediate and definitive diagnosis. The management of CS often requires multidisciplinary care teams and is challenged by data limited to small observational studies and from the high likelihood of side effects of most of the treatments currently used (eg: corticosteroids, methotrexate and TNF-alfa inhibitors).
Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine, also referred to as master regulator of the inflammatory response, involved in virtually every acute process. There is evidence that IL-1 plays a role in mouse model of sarcoidosis and human pulmonary lesions as the presence of the inflammasome in granulomas of the heart of patients with cardiac sarcoidosis, providing additional support for a role of IL-1 in the pathogenesis of CS. However, IL-1 blockade has never been evaluated as a potential therapeutic agent for cardiac sarcoidosis.
In the current study, researchers aim to evaluate the safety and efficacy of IL-1 blockade with anakinra (IL-1 receptor antagonist) in patients with cardiac sarcoidosis.
Read the detailed description
Researchers will perform an open label randomized clinical trial of anakinra (recombinant IL-1 receptor antagonist, Kineret, SOBI, Sweden) given for 4 weeks in 28 patients with cardiac sarcoidosis (defined using Heart Rhythm Society diagnostic criteria).
- Conditions
- Cardiac Sarcoidosis
- Being tested
- Anakinra
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnakinraDrug
Active Treatment
| Study group | Role | What they receive |
|---|---|---|
| Anakinra | Experimental | 100 mg/0.67 mL daily subcutaneous injection for 4 weeks Receives: Drug: Anakinra |
| Standard of Care | No intervention | Continue standard of care treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Inflammation Marker
Change in c-reactive protein in participant plasma samples
Measured: Baseline to 28 days
Secondary outcomes (1)
Change in Cardiac Fibrosis
Change in late gadolinium enhancement evident on magnetic resonance imaging (MRI) scan
Measured: Baseline to 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2019
- Study start23 Oct 2020
- Primary completion30 Jun 2024
- Study completion30 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cardiac SarcoidosisStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association, National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Sponsor
- Investigators
- Jordana Kron, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04017936
- Sponsor's protocol ID
- HM20015843
- Other IDs
- R21TR003103
- Acronym
- MAGiC-ART
- Status last verified
- Aug 2025
- First submitted
- 9 Jul 2019
- Last updated
- 7 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kron J, Crawford T, Bogun F, Jordan JH, Koelling T, Syed H, Syed A, Iden T, Polly K, Federmann EG, Bray K, Lathkar-Pradhan S, Ladd A, Dickson VM, Barron A, Tavoosi A, Beanlands R, Birnie D, Ellenbogen K, Van Tassell BW, Gregory Hundley W, Abbate A. Interleukin-1 Blockade in Cardiac Sarcoidosis: A Pilot Study. Circ Arrhythm Electrophysiol. 2023 May;16(5):e011869. doi: 10.1161/CIRCEP.123.011869. Epub 2023 Apr 24. No abstract available.
PubMed 37092332Kron J, Crawford T, Mihalick V, Bogun F, Jordan JH, Koelling T, Syed H, Syed A, Iden T, Polly K, Federmann E, Bray K, Lathkar-Pradhan S, Jasti S, Rosenfeld L, Birnie D, Smallfield M, Kang L, Fowler AB, Ladd A, Ellenbogen K, Van Tassell B, Gregory Hundley W, Abbate A. Interleukin-1 blockade in cardiac sarcoidosis: study design of the multimodality assessment of granulomas in cardiac sarcoidosis: Anakinra Randomized Trial (MAGiC-ART). J Transl Med. 2021 Nov 8;19(1):460. doi: 10.1186/s12967-021-03130-8.
PubMed 34749739
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis
- ClinicalTrials.gov ID
- NCT04017936
- Acronym / sponsor ID
- MAGiC-ART / HM20015843
- Conditions
- Cardiac Sarcoidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- American Heart Association, National Center for Advancing Translational Sciences (NCATS)
- Study start
- 23 Oct 2020 (actual)
- Primary completion
- 30 Jun 2024 (actual)
- Study completion
- 30 Jun 2024 (actual)
- First posted
- 12 Jul 2019 (actual)
- Results
- Posted 7 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sarcoidosis is a heterogeneous disorder of unknown etiology whose signature lesions are granulomatous inflammatory infiltrates in involved tissues. Tissue commonly affected are lungs, skin, eyes, lymph nodes and the heart. In this latter case, cardiac sarcoidosis (CS) can lead to atrioventricular (AV) blocks, ventricular arrhythmias, heart failure (HF) and sudden cardiac death. Similar to other involved organs, cardiac disease generally progresses from areas of focal inflammation to scar. However, the natural history of CS is not well characterized complicating an immediate and definitive diagnosis. The management of CS often requires multidisciplinary care teams and is challenged by data limited to small observational studies and from the high likelihood of side effects of most of the treatments currently used (eg: corticosteroids, methotrexate and TNF-alfa inhibitors).
Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine, also referred to as master regulator of the inflammatory response, involved in virtually every acute process. There is evidence that IL-1 plays a role in mouse model of sarcoidosis and human pulmonary lesions as the presence of the inflammasome in granulomas of the heart of patients with cardiac sarcoidosis, providing additional support for a role of IL-1 in the pathogenesis of CS. However, IL-1 blockade has never been evaluated as a potential therapeutic agent for cardiac sarcoidosis.
In the current study, researchers aim to evaluate the safety and efficacy of IL-1 blockade with anakinra (IL-1 receptor antagonist) in patients with cardiac sarcoidosis.
Detailed description
Researchers will perform an open label randomized clinical trial of anakinra (recombinant IL-1 receptor antagonist, Kineret, SOBI, Sweden) given for 4 weeks in 28 patients with cardiac sarcoidosis (defined using Heart Rhythm Society diagnostic criteria).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anakinra | Experimental | Drug: Anakinra100 mg/0.67 mL daily subcutaneous injection for 4 weeks |
| Standard of Care | No intervention | –Continue standard of care treatment |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (49 listed)
- Clinical diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society or the New Japanese Cardiac Sarcoidosis Guidelines (must meet one of the diagnostic pathways)
- Heart Rhythm Society Diagnostic Criteria based on 2 diagnostic pathways:
- Japanese Cardiac Sarcoidosis Diagnostic Criteria:
- When epithelioid granulomas are found in organs other than the heart and clinical findings strongly suggestive of the above-mentioned cardiac involvement are present (Table 1); or
- When the patient shows clinical findings strongly suggestive of pulmonary or ophthalmic sarcoidosis; at least 2 of the 5 characteristic laboratory findings of a sarcoidosis (Table 2); and clinical findings strongly suggest the above-mentioned cardiac involvement (Table 1)
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnakinraActive Treatment | Drug | Anakinra |
Primary outcome
Change in Inflammation Marker
Time frame: Baseline to 28 days
Change in c-reactive protein in participant plasma samples
1 secondary outcome
Change in Cardiac Fibrosis
Time frame: Baseline to 180 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37092332Kron J, Crawford T, Bogun F, Jordan JH, Koelling T, Syed H, Syed A, Iden T, Polly K, Federmann EG, Bray K, Lathkar-Pradhan S, Ladd A, Dickson VM, Barron A, Tavoosi A, Beanlands R, Birnie D, Ellenbogen K, Van Tassell BW, Gregory Hundley W, Abbate A. Interleukin-1 Blockade in Cardiac Sarcoidosis: A Pilot Study. Circ Arrhythm Electrophysiol. 2023 May;16(5):e011869. doi: 10.1161/CIRCEP.123.011869. Epub 2023 Apr 24. No abstract available.
- Derived from this study: PubMed 34749739Kron J, Crawford T, Mihalick V, Bogun F, Jordan JH, Koelling T, Syed H, Syed A, Iden T, Polly K, Federmann E, Bray K, Lathkar-Pradhan S, Jasti S, Rosenfeld L, Birnie D, Smallfield M, Kang L, Fowler AB, Ladd A, Ellenbogen K, Van Tassell B, Gregory Hundley W, Abbate A. Interleukin-1 blockade in cardiac sarcoidosis: study design of the multimodality assessment of granulomas in cardiac sarcoidosis: Anakinra Randomized Trial (MAGiC-ART). J Transl Med. 2021 Nov 8;19(1):460. doi: 10.1186/s12967-021-03130-8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jordana Kron, MD principal investigator
Virginia Commonwealth University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anakinra in people with Cardiac Sarcoidosis, run by Virginia Commonwealth University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 49 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Inflammation Marker (time frame: Baseline to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04017936, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.