Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
To investigate the ability of tofacitinib, a Janus kinase (JAK) inhibitor, to treat patients with cutaneous sarcoidosis and granuloma annulare during 6 months of therapy.
An open-label clinical trial of tofacitinib in cutaneous sarcoidosis and GA. The hypothesis is that Janus Kinase (JAK) 1/3 inhibition with tofacitinib will be effective for the treatment these two diseases. Tofacitinib will be administered at a dose of 5 mg twice daily and response to therapy will be assessed at months 1, 3, and 6 of therapy. The primary outcomes will be improvement in the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) and Granuloma Activity Scoring Index (GASI) after 6 months of tofacitinib therapy. Secondary outcomes will include improvement in internal organ sarcoidosis (i.e. lung, cardiac) and skin related quality of life. Pre- and on treatment PET-CT scans will be performed in patients with sarcoidosis with internal organ involvement. Pre- and on treatment blood collection and skin biopsies will be performed for correlative scientific studies using RNA sequencing, immunohistochemistry (IHC), and cytokine profiling.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with Cutaneous Sarcoidosis | Experimental | Patients with cutaneous sarcoidosis that may also have also have internal organ sarcoidosis |
|
| Patients with Granuloma Annulare | Experimental | Patients with granuloma annulare that is long-standing and/or widespread |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tofacitinib 5 mg twice daily | Drug | Tofacitinib will be administered at a dose of 5 mg twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) | For patients with sarcoidosis: change in CSAMI score after 6 months of treatment with tofacitinib compared to baseline. The activity portion of the CSAMI score will be utilized. The range of scores is from 0 to 165. Higher scores correspond with higher cutaneous disease burden. The percentage change in CSAMI score will be calculated as follows: change in CSAMI score = [baseline CSAMI - final CSAMI] / baseline CSAMI Higher percentage change corresponds to more improvement on therapy (0% = no change, 100% = complete disease resolution) Negative percentage change corresponds to disease worsening (-25% = 25% worsening of disease) | 6 - 12 months |
| Percent Change in Body Surface Area (BSA) involvement by GA lesions | For patients with GA: change in BSA involvement after 6 months of treatment with tofacitinib compared to baseline. The range of BSA involvement for this study is from 5% to 100%. Higher BSA involvement corresponds with higher cutaneous disease burden. The percentage change in BSA will be calculated as follows: Change in BSA = [baseline BSA- final BSA] / baseline BSA Higher percentage change corresponds to more improvement on therapy (0% = no change, 100% = complete disease resolution) Negative percentage change corresponds to disease worsening (-25% = 25% worsening of disease). | 6 - 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Skindex-16: a skin-related quality of life metric | For all patients: change in Skindex-16 score after 6 months of treatment with tofacitinib compared to baseline | 6 - 12 months |
| Change in Histologic Findings |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| William Damsky, MD, PhD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale Center for Clinical Investigation | New Haven | Connecticut | 06519 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30586518 | Background | Damsky W, Thakral D, Emeagwali N, Galan A, King B. Tofacitinib Treatment and Molecular Analysis of Cutaneous Sarcoidosis. N Engl J Med. 2018 Dec 27;379(26):2540-2546. doi: 10.1056/NEJMoa1805958. | |
| 35668129 | Derived | Damsky W, Wang A, Kim DJ, Young BD, Singh K, Murphy MJ, Daccache J, Clark A, Ayasun R, Ryu C, McGeary MK, Odell ID, Fazzone-Chettiar R, Pucar D, Homer R, Gulati M, Miller EJ, Bosenberg M, Flavell RA, King B. Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis. Nat Commun. 2022 Jun 6;13(1):3140. doi: 10.1038/s41467-022-30615-x. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D016460 | Granuloma Annulare |
| ID | Term |
|---|---|
| D017441 | Necrobiotic Disorders |
| D003095 | Collagen Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C479163 | tofacitinib |
Not provided
Not provided
Not provided
open-label trial
Not provided
Not provided
Not provided
Not provided
|
Skin biopsies of lesional skin will be performed at baseline and again after 6 months of treatment. Standard hematoxylin and eosin (H&E) and immunohistochemistry for CD68, phospho-STAT1, and phospho-STAT3 will be performed.
| 6 -12 months |
| Change in RNA sequencing markers (gene expression analysis) | RNA sequencing will be performed on RNA extracted from skin biopsies of lesional skin at baseline and again after 6 months of treatment. | 6 - 12 months |
| Change in cytokine biomarkers | Luminex-based cytokine analysis using a commercially available service will be performed on plasma collected at baseline and again after 6 months of treatment. | 6 - 12 months |
| Change in activity of internal organ sarcoidosis | For patients with sarcoidosis: change in PET-CT imaging after 6 months of treatment with tofacitinib compared to baseline | 6 - 12 months |
| 33317858 | Derived | Wang A, Rahman NT, McGeary MK, Murphy M, McHenry A, Peterson D, Bosenberg M, Flavell RA, King B, Damsky W. Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib. J Allergy Clin Immunol. 2021 May;147(5):1795-1809. doi: 10.1016/j.jaci.2020.10.012. Epub 2020 Dec 11. |
| D012871 | Skin Diseases |
| D006099 | Granuloma |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |