A Trial of Baricitinib in Patients With Cardiac Sarcoidosis

Official title

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

Overview

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

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

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Stanford University — Palo Alto

Identifiers

NCT: NCT06868381 · 79204

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗