Janus Kinase Inhibition in Granuloma Annulare

William Damsky

Status and phase

Active, not recruiting

Phase 2

Conditions

Granuloma Annulare

Treatments

Drug: Abrocitinib 200 mg

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT05650736

2000033312

No NIH funding (Other Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment

10 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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