Cardiac Sarcoidosis
Conditions
Keywords
baricitinib, sarcoidosis, cardiac sarcoidosis, Janus kinase inhibitor, JAK inhibitor
Brief summary
The goal of this clinical trial is to learn if baricitinib in combination with a background steroid-sparing medication can treat active cardiac sarcoidosis in adults. The main question it aims to answer is: \- In patients with active cardiac sarcoidosis, does treatment with baricitinib improve cardiac sarcoidosis disease activity as assessed by changes on cardiac FDG-PET/CT? Participants will: * Take baricitinib in combination with a steroid-sparing therapy for up to 16 weeks * Visit the clinic every two to four weeks for checkups and tests * Be asked to complete questionnaires to see how they feel on baricitinib and medication diaries to record when they take baricitinib
Interventions
baricitinib 4 mg tablet taken orally once daily
Sponsors
Stanford University
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of cardiac sarcoidosis based on one of the following pathways: * Histological Diagnosis * Myocardial or extracardiac biopsy demonstrating non-caseating granuloma with no alternative cause identified AND * Abnormal FDG uptake on cardiac PET-CT conducted within six weeks of Screening, in a pattern consistent with active cardiac sarcoidosis AND * Exclusion of other causes for cardiac manifestations * Clinical Diagnosis * One or more of the following is present: * Steroid +/- immunosuppressant responsive cardiomyopathy or heart block * Unexplained reduced LVEF (\< 40%) and/or segmental wall motion abnormalities not related to coronary artery disease or another defined cause * Unexplained sustained (spontaneous or induced) VT * Mobitz type II 2nd degree heart block or 3rd degree heart block * CT chest and/or FDG PET-CT showing features consistent with pulmonary sarcoidosis and/or hilar lymphadenopathy AND * Abnormal FDG uptake on cardiac PET-CT conducted within 6 weeks of Screening, in a pattern consistent with active cardiac sarcoidosis AND * Exclusion of other causes for cardiac manifestations * Active cardiac sarcoidosis based on abnormal FDG uptake on cardiac PET-CT conducted within six weeks of Screening, in a pattern consistent with active cardiac sarcoidosis * No current treatment with immunosuppressive medications other than a steroid-sparing medication (including methotrexate, leflunomide, azathioprine, or mycophenolate mofetil), and/or prednisone (or equivalent) at a dose of ≤ 20mg daily at Baseline Key
Exclusion criteria
* Receipt of a non-biologic DMARD or immunosuppressive agent other than methotrexate, leflunomide, azathioprine, mycophenolate mofetil, hydroxychloroquine, or glucocorticoids within 28 days prior to screening * Receipt of a bDMARD or tsDMARD, including non-depleting B-cell-directed therapy (eg, belimumab), T cell costimulatory blockade (eg, abatacept), TNF-alpha inhibition (eg, infliximab, adalimumab, etanercept, golimumab, certolizumab pegol), interleukin-6 inhibition (eg, tocilizumab, sarilumab), interleukin-1 inhibition (eg, anakinra), JAK inhibition (eg, tofacitinib, upadacitinib, baricitinib), or other biologic immunomodulatory agent within 28 days prior to screening * Receipt of any biologic B cell-depleting therapy (eg, rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab) in the 6 months prior to screening; receipt of such a B cell-depleting agent in the period 6-12 months prior to screening is exclusionary unless B cell counts have returned to ≥ LLN * History of venous thromboembolism (VTE) or an increased risk for VTE * Current smoking * Estimated glomerular filtration rate \< 30 mL/min/1.73 m2 by Modification of Diet in Renal Disease Study (MDRD) equation * Blood tests at screening that meet any of the following criteria: * Hemoglobin \< 7.5 g/dL * Neutrophils \< 1000/mm3 * Absolute lymphocyte count \< 500/mm3 * Platelets \< 100 x 109/L * Subjects with the following abnormal liver function tests: * Aspartate aminotransferase (AST) \> 2x ULN * Alanine aminotransferase (ALT) \> 2x ULN * Total bilirubin (TBL) \> 2x ULN unless AST, ALT, and hemoglobin are within central laboratory normal range and the patient has a known history of Gilbert syndrome * Active, clinically significant infection at the time of Screening * Active malignancy or history of malignancy that was active within the last 5 years, except as follows: * In situ carcinoma of the cervix following apparently curative therapy \> 12 months prior to screening, * Cutaneous basal cell or squamous cell carcinoma following apparently curative therapy, or * Prostate cancer treated with radical prostatectomy or radiation therapy with curative intent \> 3 years prior to screening and without known recurrence or current treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with resolution of cardiac FDG uptake on PET-CT | From baseline to end of treatment at 16 weeks | Resolution of FDG uptake will be determined by the consensus of two blinded nuclear medicine radiologists, in accordance with current SNMMI and ASNC guidelines |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent change in FDG avidity (SUVmax) in the cardiac lesion with greatest FDG avidity on PET-CT | From baseline to 8 weeks and end of treatment at 16 weeks | — |
| Percent change in total cardiac metabolic activity on FDG PET-CT | From baseline to 8 weeks and end of treatment at 16 weeks | Total cardiac metabolic activity is total lesion glycolysis within the heart |
| Proportion of patients with resolution of extracardiac FDG uptake on PET-CT | From baseline to 8 weeks and end of treatment at 16 weeks | — |
| Percent change in FDG avidity (SUVmax) in up to six extracardiac lesions on PET-CT | From baseline to 8 weeks and end of treatment at 16 weeks | — |
| Percent change in total extracardiac metabolic activity on FDG PET-CT | From baseline to 8 weeks and end of treatment at 16 weeks | Total extracardiac metabolic activity is total lesion glycolysis of extracardiac disease |
| Proportion of patients with resolution of cardiac FDG uptake on PET-CT | From baseline to 8 weeks and end of follow-up at 28 weeks | — |
| Change in sarcoidosis disease activity assessment | From baseline to 8 weeks and end of treatment at 16 weeks | Sarcoidosis disease activity assessed with King's Sarcoidosis Questionnaire. Total score range: 0 to 100, with 100 indicating the highest quality of life |
| Change in fatigue assessment | From baseline to 8 weeks and end of treatment at 16 weeks | Fatigue assessed with FACIT-F. Total score range: 0-52, lower scores correspond with more fatigue |
| Change from Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | From baseline to 8 weeks and end of treatment at 16 weeks | Physician rates patient's disease on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state |
| Change from Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | From baseline to 8 weeks and end of treatment at 16 weeks | Patient rates their disease on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state |
| Changes in ACE laboratory assessment | From baseline to 8 weeks and end of treatment at 16 weeks | — |
| Changes in high-sensitivity troponin I laboratory assessment | From baseline to 8 weeks and end of treatment at 16 weeks | — |
| Changes in NT-proBNP laboratory assessment | From baseline to 8 weeks and end of treatment at 16 weeks | — |
| Changes in total IgG laboratory assessment | From baseline to 8 weeks and end of treatment at 16 weeks | — |
| Changes in ESR laboratory assessment | From baseline to 8 weeks and end of treatment at 16 weeks | — |
| Changes in CRP laboratory assessment | From baseline to 8 weeks and end of treatment at 16 weeks | — |
| Number of participants with safety endpoints of interest | From screening to end of follow-up at 28 weeks | Safety endpoints of interest include hospitalization for cardiac events, implantation of a left ventricular assist device (LVAD), cardiac transplantation, mortality |
Countries
United States
Contacts
CONTACTAngie Aberia
CONTACTTravis Deal
PRINCIPAL_INVESTIGATORMatthew C Baker, MD, MS
Stanford University
Outcome results
None listed