To investigate the role of an oral TYK2 inhibitor for the treatment of patients with moderate to severe sarcoidosis with cutaneous involvement (CSAMI score of 10 or greater) and GA (defined as a BSA involvement of at least 5%), which are difficult to treat.
Primary Objective To determine if TYK2 specific inhibition is effective in treating sarcoidosis and granuloma annulare (GA), problematic granulomatous inflammatory diseases which are difficult to treat. Secondary Objective To determine the effect of treatment of participants' quality of life and on biomarkers of disease activity which often involves internal organ changes in sarcoidosis patients.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
6 mg twice daily
YCCI/Church Street Research Unit (CSRU)
New Haven, Connecticut, United States
Percent change in the BSA involvement of GA
The percent change in the BSA involvement of GA after 6 months of treatment for participants with moderate to severe GA affecting at least 5% body surface area (BSA).
Time frame: Baseline and 6 months post-treatment
Percent change in the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) score
The percent change in the CSAMI after 6 months of treatment. CSAMI evaluates the severity of sarcoidosis lesions in sarcoidosis participants across different body areas with separate scales for "Activity" (assessing inflammation, induration, surface changes, and area of involvement) and "Damage" (assessing post-inflammatory changes like scarring and dyspigmentation), resulting in a total Activity score ranging from 0 to 165 and a total Damage score from 0 to 22; with, higher scores indicating greater disease severity.
Time frame: Baseline and 6 months post-treatment
Changes in molecular signatures in skin before and after treatment
Changes in molecular signatures in skin at baseline vs. after 6 months of treatment. RNA-sequencing will be used to examine transcriptional profiles in this skin.
Time frame: Baseline and 6 months post-treatment
Changes in molecular signatures in blood before and after treatment
Changes in molecular signatures in blood at baseline vs. after 6 months of treatment. A high throughput proteomic assay will be used to examine molecular profiles in the blood.
Time frame: Baseline and 6 months post-treatment
Changes in Skindex-16 (Skin related quality of life index)
Changes in Skindex-16 (Skin related quality of life index) baseline vs. after 6 months of treatment. This is a 16 item validated skin related Quality of Life questionnaire which will be administered by the study team to assess how GA affects the participants quality of life. Scores range from 0-96, higher scores indicating more significant impact on quality of life.
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Time frame: Baseline and 6 months post-treatment
Changes in Granuloma Annulare Severity and Morphology Instrument (GASMI) score
Changes in GASMI score baseline vs. after 6 months of treatment. The Granuloma Annulare Severity and Morphology Instrument is a clinical severity scoring tool for GA. The score is determined by the study team who will examine the participants skin to determine the severity of the GA in different anatomic areas. Scores range from 0-165 with higher score indicating a worse outcome.
Time frame: Baseline and 6 months post-treatment
Organ involvement on whole body PET
Percent change in organ involvement using whole body PET- CT imaging
Time frame: Baseline and 6 months post-treatment
King's Sarcoidosis Questionnaire (KSQ)
The KSQ is a self-administered questionnaire used to assess the health-related quality of life in patients with sarcoidosis. Total score range is from 0 to 100 with higher scores indicating better health status.
Time frame: Baseline and 6 months post-treatment
Sarcoidosis Fatigue Assessment Scale (FAS)
The FAS is a 10-item self-report questionnaire used to measure the severity of fatigue in individuals with sarcoidosis, where each item is rated on a 5-point Likert scale ranging from "never" to "always". Total score is calculated by summing up all responses with a total score range from 10 (minimal fatigue) to 50 (extreme fatigue). Higher scores indicate greater fatigue.
Time frame: Baseline and 6 months post-treatment
Rhinosinusitis Disability Index (RSDI)
The RSDI is a 30-item questionnaire used to assess the impact of rhinosinusitis on a patient's quality of life. Each question is rated on a scale from 0 ("never") to 4 ("always") with a total score ranging from 0 to 120. Higher scores indicate greater disability,
Time frame: Baseline and 6 months post-treatment