Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis

NCT04017936 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: HM20015843R21TR003103
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Cardiac Sarcoidosis

Outcome Measures

Primary Outcomes (1)

• Change in Inflammation Marker

  Change in c-reactive protein in participant plasma samples

  Baseline to 28 days

Secondary Outcomes (1)

• Change in Cardiac Fibrosis

  Baseline to 180 days

Study Arms (2)

Anakinra

EXPERIMENTAL

100 mg/0.67 mL daily subcutaneous injection for 4 weeks

Drug: Anakinra

Standard of Care

NO INTERVENTION

Continue standard of care treatment

Interventions

Anakinra DRUG

Active Treatment

Anakinra

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• or more of the 5 major criteria (a)-(e) are satisfied.
• of the 5 major criteria (a)-(e) and 2 or more of the 3 minor criteria (f)-(h) are satisfied.
• \. Major criteria
• High-grade AV block (including complete AV block) or fatal ventricular arrhythmia (e.g., sustained VT and VF)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• American Heart Association: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (2)

University of Michigan Sarcoidosis Clinic

Ann Arbor, Michigan, 48109, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (2)

• 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.

  PMID: 37092332 RESULT

• Kron 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.

  PMID: 34749739 DERIVED

MeSH Terms

Interventions

Interleukin 1 Receptor Antagonist Protein

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Jordana Kron, MD
• Organization: Virginia Commonwealth University

jordana.kron@vcuhealth.org

804-828-7565

Study Officials

• Jordana Kron, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: July 12, 2019
• Study Start: October 23, 2020
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: August 7, 2025
• Results First Posted: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)