A Trial of Baricitinib in Patients With Cardiac Sarcoidosis

Официальное название

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

Обзор

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

Вмешательства

• Препарат Baricitinib (LY3009104) 4 mg
  baricitinib 4 mg tablet taken orally once daily

Первичные конечные точки

• Proportion of patients with resolution of cardiac FDG uptake on PET-CT [Срок оценки: From baseline to end of treatment at 16 weeks]

Вторичные конечные точки (12)

• Percent change in FDG avidity (SUVmax) in the cardiac lesion with greatest FDG avidity on PET-CT [Срок оценки: From baseline to 8 weeks and end of treatment at 16 weeks]
• Percent change in total cardiac metabolic activity on FDG PET-CT [Срок оценки: From baseline to 8 weeks and end of treatment at 16 weeks]
• Proportion of patients with resolution of extracardiac FDG uptake on PET-CT [Срок оценки: 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 [Срок оценки: From baseline to 8 weeks and end of treatment at 16 weeks]
• Percent change in total extracardiac metabolic activity on FDG PET-CT [Срок оценки: From baseline to 8 weeks and end of treatment at 16 weeks]
• Proportion of patients with resolution of cardiac FDG uptake on PET-CT [Срок оценки: From baseline to 8 weeks and end of follow-up at 28 weeks]
• Change in sarcoidosis disease activity assessment [Срок оценки: From baseline to 8 weeks and end of treatment at 16 weeks]
• Change in fatigue assessment [Срок оценки: From baseline to 8 weeks and end of treatment at 16 weeks]
• Change from Baseline in Physician Disease Activity Visual Analogue Scale (VAS) [Срок оценки: From baseline to 8 weeks and end of treatment at 16 weeks]
• Change from Baseline in Patient Disease Activity Visual Analogue Scale (VAS) [Срок оценки: From baseline to 8 weeks and end of treatment at 16 weeks]
• Changes in ACE laboratory assessment [Срок оценки: From baseline to 8 weeks and end of treatment at 16 weeks]
• Changes in high-sensitivity troponin I laboratory assessment [Срок оценки: From baseline to 8 weeks and end of treatment at 16 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Stanford University — Palo Alto

Идентификаторы

NCT: NCT06868381 · 79204

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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