Clinical trial NCT06725264: Tyrosine Kinase 2 (TYK2) for GA and CS
Official title: TYK2 Inhibition in Granuloma Annulare (GA) and Cutaneous Sarcoidosis (CS): an Opportunity for Pathogenesis Directed Therapy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Sarcoidosis
Granuloma Annulare
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2024-12-10
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Male and female subjects at least 18 years of age with moderate to severe granuloma annulare or cutaneous sarcoidosis affecting at least 5%body surface area.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Male and female patients 18 years old or older
* Diagnosis of GA or cutaneous sarcoidosis with supportive skin biopsy
* BSA involvement of at least 5% (GA) or CSAMI numerical score of at least 10 (sarcoidosis)
* If patients are on systemic therapies or phototherapy for their GA, they must discontinue these therapies with a washout period of 4 weeks and must remain off them during the study
* If patients are on topical therapies for their GA, they must discontinue these therapies with a washout period of 2 weeks and must remain off them during the study
* If patients are taking other systemic therapies for their sarcoidosis, they must be taking a stable dose of the other medication(s) for at least 3 months with no plans to change the regimen in the next 6 months. With the exception of methotrexate or low dose prednisone (20 mg or less per day), use of concomitant immunosuppressants, e.g. infliximab, azathioprine, etc., will not be permitted.
* For sarcoidosis, washout of topical medications will be for 2 weeks.
* Washout for oral medications will not be possible in most cases. Patients will be allowed to continue concomitant prednisone (up to 20 mg daily) or weekly methotrexate (up to 15 mg daily).
* Females of childbearing potential must agree to use birth control during the study and there must be a negative pregnancy test documented prior to starting the medication.
* Patients must be willing to have skin biopsies, blood collection, and total body photography and to comply with clinic visits

Exclusion Criteria:

* Age \<18 years old
* Patients with a history of malignancy (except history of successfully treated basal cell or squamous cell carcinoma of the skin)
* Patients known to be HIV or hepatitis B or C positive, or have an active, serious infection herpes simplex, herpes zoster, and pneumonia. This would also include localized infections.
* Patients with positive tuberculin skin test or positive QuantiFERON® TB test
* Patients with significant hepatic impairment
* Patients with moderate renal impairment
* Patients with uncontrolled peptic ulcer disease
* Patients with a history of deep vein thrombosis and/or pulmonary embolism and/or clotting disorder
* Patients with any history of myocardial infarction or stroke.
* Patients taking concomitant immunosuppressive medications, with the exception of methotrexate and/or low-dose prednisone, including but not limited to mycophenolate mofetil, azathioprine, tacrolimus, cyclosporine, or TNF-α inhibitors
* Women of childbearing potential who are unable or unwilling to use birth control while taking the medication
* Women who are pregnant or nursing
* Current smoker or history of any tobacco use
* Patients over 50 who have the presence of cardiovascular risk factor
* Screening labs outside the normal range for parameters associated with potential risk for treatment under investigation. Including but not limited to:

  i. Platelets \<150,000/mm3, ii. Absolute neutrophil count \<1,000/mm3, iii. Hemoglobin levels \<8 g/dL, iv. Absolute lymphocyte count \<500/mm3
* Patients who are taking clinically significant inhibitors of both CYP2C19 and CYP2C9, or strong CYP2C19 or CYP2C9 inducers, as well as P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities.
* Patients who have received a live vaccine. Patients should wait a minimum of 2 weeks, if recently vaccinated, prior to initiating treatment and should not receive a live vaccine during treatment or 2 weeks post-treatment.
* Patients with any medical, psychiatric, or social condition that is likely to unfavorably affect the risk-benefit of continued study participation, interfere with study compliance or confound safety or efficacy assessments

Primary outcomes:
measure: Percent change in the BSA involvement of GA
timeFrame: Baseline and 6 months post-treatment
measure: Percent change in the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) score
timeFrame: Baseline and 6 months post-treatment
Secondary outcomes:
measure: Changes in molecular signatures in skin before and after treatment
timeFrame: Baseline and 6 months post-treatment
measure: Changes in molecular signatures in blood before and after treatment
timeFrame: Baseline and 6 months post-treatment
measure: Changes in Skindex-16 (Skin related quality of life index)
timeFrame: Baseline and 6 months post-treatment
measure: Changes in Granuloma Annulare Severity and Morphology Instrument (GASMI) score
timeFrame: Baseline and 6 months post-treatment
measure: Organ involvement on whole body PET
timeFrame: Baseline and 6 months post-treatment
measure: King's Sarcoidosis Questionnaire (KSQ)
timeFrame: Baseline and 6 months post-treatment
measure: Sarcoidosis Fatigue Assessment Scale (FAS)
timeFrame: Baseline and 6 months post-treatment
measure: Rhinosinusitis Disability Index (RSDI)
timeFrame: Baseline and 6 months post-treatment
Other outcomes:
Locations:
city: New Haven
country: United States
facility: YCCI/Church Street Research Unit (CSRU)
state: Connecticut
Study officials:
affiliation: Yale University
name: William Damsky, MD
role: PRINCIPAL_INVESTIGATOR
References: