Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis

• Register: ClinicalTrials.gov
• Last refreshed on: 13 November 2023
• Main ID: NCT04017936
• Date of registration: 09/07/2019
• Prospective Registration: Yes
• Primary sponsor: Virginia Commonwealth University
• Public title: Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis MAGiC-ART
• Scientific title: Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis
• Date of first enrolment: October 23, 2020
• Target sample size: 28
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04017936
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Jordana Kron, MD
• Affiliation: Virginia Commonwealth University

• Name: Jordana Kron, MD

Key inclusion & exclusion criteria

INCLUSION CRITERIA (all 3 criteria need to be met)

- 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:

1. 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);

2. 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:

1. 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.

2. Clinical diagnosis group (those with negative myocardial biopsy findings or those
not undergoing myocardial biopsy)

The patient is clinically diagnosed as having sarcoidosis:

1. 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

2. 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.

1. 2 or more of the 5 major criteria (a)-(e) are satisfied.

2. 1 of the 5 major criteria (a)-(e) and 2 or more of the 3 minor criteria (f)-(h) are
satisfied.

1. Major criteria

1. High-grade AV block (including complete AV block) or fatal ventricular arrhythmia
(e.g., sustained VT and VF)

2. Basal thinning of the ventricular septum or abnormal ventricular wall anatomy
(ventricular aneurysm, thinning of the middle or upper ventricular septum, regional
wall thickening

3. Left ventricular contractile dysfunction (LVEF < 50%)

4. 67Ga citrate scintigraphy or 18F-FDG PET reveals abnormally high tracer accumulation
in the heart

5. Gadolinium-enhanced MRI revealed delayed contrast enhancement of the myocardium 2.
Minor criteria

6. Abnormal ECG findings: Ventricular arrhythmias (nonsustained VT, multifocal or
frequent premature ventricular contractions, bundle branch block, axis deviation, or
abnormal Q waves

7. Perfusion defects on myocardial perfusion scintigraphy (SPECT)

8. 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

1. 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.)

2. 67Ga scintigraphy or 18F-FDG PET reveals no abnormal tracer accumulation in any
organs other than the heart.

3. A chest CT scan reveals no shadow along the lymphatic tracts in the lungs or no
hilar and mediastinal lymphadenopathy (minor axis>10 mm).

1. Histological diagnosis group Isolated cardiac sarcoidosis is diagnosed
histologically when endomyocardial biopsy or surgical specimens demonstrate
non-caseating epithelioid granulomas.

2. 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)

1. Age<21 years;

2. Pregnancy;

3. Inability to obtain consent from patient or legally authorized representative;

4. 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);

5. Severe anemia (Hgb<8 g/dl - due to the need of more frequent blood sampling with this
study).

6. Acute or chronic active infections (not including treated/cured HCV with negative
viral load).

7. 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).

8. Active acute or chronic psychiatric illness that in the opinion of the investigator
may prevent from complying with study instructions;

9. Limited English Proficiency that in the opinion of the investigator may prevent from



Age minimum: 21 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cardiac Sarcoidosis

Intervention(s)

Drug: Anakinra

Primary Outcome(s)

Change in inflammation marker [Time Frame: Baseline to 28 days]

Secondary Outcome(s)

Change in cardiac fibrosis [Time Frame: Baseline to 28]

Change in cardiac inflammation [Time Frame: Baseline to 28]

Number of serious cardiac events [Time Frame: 28 days]

Secondary ID(s)

R21TR003103

HM20015843

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

American Heart Association

National Center for Advancing Translational Sciences (NCATS)