Tyrosine Kinase 2 (TYK2) for GA and CS

Phase 2

Withdrawn

• Conditions: Sarcoidosis; Granuloma Annulare
• Interventions: Drug: Deucravacitinib

• Registration Number: NCT06725264
• Lead Sponsor: Yale University

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.

Study Timeline

• Study First Submitted: 2024-12-05
• Study First Submitted QC: 2024-12-05
• Study First Posted: 2024-12-10
• Study Start: 2025-03
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-29
• Primary Completion: 2026-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Granuloma Annulare	Deucravacitinib	Participants with GA will receive the TYK2 inhibitor deucravacitinib 6mg twice daily
Cutaneous Sarcoidosis	Deucravacitinib	Participants with CS will receive the TYK2 inhibitor deucravacitinib 6mg twice daily

Primary Outcome Measures

Name	Time	Method
Percent change in the BSA involvement of GA	Baseline and 6 months post-treatment	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).
Percent change in the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) score	Baseline and 6 months post-treatment	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.

Secondary Outcome Measures

Name	Time	Method
Changes in molecular signatures in skin before and after treatment	Baseline and 6 months post-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.
Changes in molecular signatures in blood before and after treatment	Baseline and 6 months post-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.
Changes in Skindex-16 (Skin related quality of life index)	Baseline and 6 months post-treatment	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.
Changes in Granuloma Annulare Severity and Morphology Instrument (GASMI) score	Baseline and 6 months post-treatment	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.
Organ involvement on whole body PET	Baseline and 6 months post-treatment	Percent change in organ involvement using whole body PET- CT imaging
King's Sarcoidosis Questionnaire (KSQ)	Baseline and 6 months post-treatment	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.
Sarcoidosis Fatigue Assessment Scale (FAS)	Baseline and 6 months post-treatment	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.
Rhinosinusitis Disability Index (RSDI)	Baseline and 6 months post-treatment	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,

Trial Locations

Locations (1)

YCCI/Church Street Research Unit (CSRU); 🇺🇸 New Haven, Connecticut, United States