Rilonacept in Subjects With Cardiac Sarcoidosis

Mayo Clinic

Status and phase

Enrolling

Phase 2

Conditions

Cardiac Sarcoidosis

Treatments

Drug: Rilonacept

Study type

Interventional

Funder types

Other

Identifiers

NCT06660732

23-013175

Details and patient eligibility

About

The primary objective of this study is to evaluate the effect of rilonacept, added to standard therapy and compared with standard therapy alone, on improvement in myocardial inflammation in subjects with cardiac sarcoidosis after 24 weeks of therapy.

Enrollment

60 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Able to comprehend and willing to sign an ICF and to abide by the study restrictions and requirements
Age ≥ 18 years and ≤ 80 years
Female subjects must be:
- postmenopausal, defined as at least 12 months post cessation of menses (without an alternative medical cause), or
- permanently sterile following documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation, or having a male partner with vasectomy as affirmed by the subject, or
- nonpregnant, nonlactating, and having agreed to use an effective method of contraception (i.e., hormonal contraception, intrauterine device [IUD], or double barrier methods such as condom plus diaphragm or diaphragm plus spermicide or condom plus spermicide) from Screening Visit 1 until 5 months after study drug administration, if sexually active.
Male subjects must have documented vasectomy or must use double barrier methods of contraception (such as condom plus diaphragm or diaphragm plus spermicide or condom plus spermicide) or use condoms plus hormonal contraceptives or condoms plus IUD with their female partners of childbearing potential from randomization to 3 months after the last dose of study drug administration. Male subjects must agree to refrain from donating sperm during this time period.
Has completed recommended vaccinations per current guidelines prior to first dose of study drug

Cardiac Inclusion Criteria:
Has a diagnosis of cardiac sarcoidosis by the Heart Rhythm Society (HRS) expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis, or the Japanese Circulation Society 2016 Guideline on diagnosis and treatment of cardiac sarcoidosis (Terasaki 2019)
Three or more segments of active FDG uptake on PET scan within 8 weeks of randomization, despite standard therapy
Willing to wear an ambulatory cardiac rhythm monitor at the specified timepoints

Exclusion Criteria

Unable or unwilling to provide informed consent
Weight >380 pounds (172 kilograms)
Women who are pregnant or lactating or women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
Planned to initiate TNF-α antagonist therapy over the course of the study.
Known claustrophobia, or difficulty completing prior PET scan procedure(s)
Left ventricular end-systolic diameter (LVESD) > 60 mm on echocardiogram
Other systemic immune disorder(s) or other disorder(s) that require treatment with immunomodulators or immunosuppressants
Has received, or is scheduled to receive after randomization, mechanical circulatory support
Congenital, valvular, and/or coronary artery disease that could explain the severity of cardiac dysfunction
Known hypersensitivity to Rilonacept or to any of its excipients
Meets the following TB criteria:
1. History of active TB prior to screening OR
2. History of latent TB that was not adequately treated prior to screening OR
3. Signs or symptoms suggestive of active TB (e.g., new cough of >14 days in duration or a change in chronic cough, persistent fever, unintentional weight loss, or night sweats) upon review of medical history and/or physical examination at screening OR
4. Recent close contact with a person with active TB OR
5. Positive or indeterminate Interferon Gamma Release Assay (IGRA) test results or results from another positive TB test at screening based on acceptable local clinical practice
Use of the following immunosuppressive or immunomodulatory therapies (see also Section 5.6 "Prior and Concomitant Therapy") within the timeframe prior to randomization as defined below for each drug class or category:
1. INCREASE in dose of existing immunosuppression/immunomodulation drug or INITIATION of new immunosuppression/immunomodulation drug in the one month prior to or ON or AFTER the date of the eligibility/baseline FDG-PET scan until the date of randomization.
2. Anakinra within 1 week prior to first dose of study drug; canakinumab within 8 weeks prior to the first dose of study drug; abatacept within 8 weeks prior to first dose of study drug;
3. TNF inhibitors within 2-8 weeks of or 5 half-lives (etanercept within 2 weeks; infliximab, certolizumab, golimumab, or adalimumab within 8 weeks) prior to first dose of study drug, whichever is longer.
4. Rituximab within 6 months prior to the first dose of study drug unless levels of CD20+ B cells have been assessed and have returned to normal.
5. Cyclosporine A (CsA) within 4 weeks prior to the first dose of study drug.
Received any investigational product within 30 days or 5 half-lives (if the half-life is known) of an investigational product (whichever is longer) prior to first dose of study drug
Concurrent enrollment in another clinical study, with the exception of observational studies
Uncontrolled hypertension (systolic blood pressure >170 mmHg and diastolic blood pressure >110 mmHg
Uncontrolled thyroid disease (serum TSH < 0.1 mU/L or > 10 mU/L)
Uncontrolled diabetes mellitus (serum glucose > 180 mg/dL fasting or HbA1c >8%)
Estimated glomerular filtration rate (eGFR) (eGFR) <30mL/min
Major surgery within 8 weeks prior to screening or planned major surgery within 6 months after first dose of study drug.
Transplanted organs (except corneal transplant performed more than 3 months prior to first dose of study drug).
Severe active, recurrent, or chronic infection (per PI discretion), or any episode of infection requiring hospitalization or treatment with a course of IV antibiotics within 12 weeks before screening. Subjects with a history of severe opportunistic infection (per PI discretion) are also excluded from the study.
High risk of infection (e.g., history of hereditary or acquired immune deficiency disorder), a history of an infected joint prosthesis at any time with that prosthesis still in situ, leg ulcers, indwelling urinary catheter, or persistent or recurrent chest infections.
Chronic active HBV infection, defined as:
1. HBV surface antigen positive
2. HBV anti-core antibody positive but anti-surface antibody negative
Presence of symptoms indicative of COVID-19 infection (per PI discretion), unless a PCR test for COVID-19 has been reported as negative within the previous 7 days or is acquired prior to randomization.
History of cancer within the last 5 years from screening, except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured.
Has screening laboratory test results meeting any of the following criteria:
1. Hemoglobin level < 8.0 g/dL
2. WBC count < 3.0 × 103/µL
3. Neutrophil count <1.5 × 103/µL
4. Platelet count < 100 × 103/µL
5. Total bilirubin level >1.5 × ULN unless the test results are consistent with those for Gilbert's syndrome
6. AST or ALT values > 2 × ULN
Any condition that, in the opinion of the investigator, could interfere with evaluation of the investigational product or interpretation of subject safety or confound the results of the study