A Trial of Baricitinib in Patients With Cardiac Sarcoidosis

A Phase IIa, Single-Site, Open-Label Trial of Baricitinib in Patients With Cardiac Sarcoidosis

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

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