Clinical trial NCT05650736: Janus Kinase Inhibition in Granuloma Annulare
Official title: JAK1 Inhibition in Granuloma Annulare: an Opportunity for Pathogenesis Directed Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Granuloma Annulare
Keywords: Granuloma Annulare
Inhibition
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Yale University
name: Pfizer
First posted: 2022-12-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: moderate to severe GA affecting at least 5% body surface area
Primary purpose: TREATMENT

Brief summary: The primary objective is to determine if JAK1 specific inhibition is effective in treating granuloma annulare (GA), a problematic inflammatory skin disease without an FDA approved treatment. The primary outcome will be the percentage change in the body surface area (BSA) involvement by GA after 6 months of treatment with abrocitinib 200 mg daily in 10 patients with moderate to severe GA affecting at least 5% body surface area (BSA).

Detailed description: There are no effective treatments for GA. Systemic corticosteroids can be effective in temporarily controlling GA; however, GA patients are almost never treated with systemic steroids due to the myriad potential adverse effects of this drug class and its transient effect on disease control. Intralesional (intradermal) steroid injections can be effective in patients with localized GA but are not really an option for patients with BSA \> 1-2%, require frequent clinic visits for injection, are painful, and also only transiently control disease. A variety of other treatment approaches have been described and include: antibiotics (minocycline, doxycycline, others), hydroxychloroquine, phototherapy, tumor necrosis factor inhibitors, among others. However, these therapies are rarely effective. GA is notoriously recalcitrant to treatment.

With no FDA approved therapies for GA and current approaches being broadly ineffective; there is a large unmet need for an effective treatment. Likely in part because of under recognition, GA is designated as a rare disease by the National Organization for Rare Disorders. Progress in the treatment of GA has been impaired by a poor understanding of disease pathogenesis. Not only will this study allow for greater clarity regarding the pathogenesis of GA, but an oral treatment option for patients that is easier to administer compared to other therapies (such as injections) and with less potential systemic side effects.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Male and female patients 18 years old or older
* Diagnosis of GA with supportive skin biopsy
* BSA involvement of at least 5%
* 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
* 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® Tuberculosis 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
* 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 moderate to strong 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: Percentage Change in BSA involvement by active GA
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Changes in Granuloma Annulare Severity and Morphology Instrument (GASMI) score
timeFrame: Baseline and 6 months
measure: Changes in Skindex-16 (Skin related quality of life index)
timeFrame: Baseline and 6 months
measure: Changes in molecular signatures in skin and blood before and after treatment
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: William Damsky, M.D.
role: PRINCIPAL_INVESTIGATOR
References: