Baricitinib in the Treatment of Adults With Pyoderma Gangrenosum (PG)

Inclusion Criteria:

• Willingness to comply with study procedures/requirements

• Capable of giving informed consent

• Diagnosis of at least one PG ulcer by clinical, histological and laboratoryassessments with a minimum wound size of 4 cm2.

• Male age 18-99 who agree to not father a child or donate sperm while on study and atleast 1 week following last dose of the study drug. If subject is a sexually activemale and could cause a pregnancy, subject must be sure that female partner(s) areusing birth control that works well or not have sex.

• Female age 18-99; either of non-childbearing potential or of childbearing potentialwho test negative for pregnancy and agree to use at least two reliable methods ofbirth control or remain abstinent during the study and for at least 1 week followingthe last dose of baricitinib.

• Classic PG defined as deep ulceration with undermining violaceous borders.

• Are candidate for systemic therapy. All participants will be taking and clinicallystable 30 mg (same ulcer size) of prednisone fort least two weeks at the start ofthe study. Patients must have discontinued immunosuppressive therapies (cyclosporine, azathioprine, mycophenolate mofetil, methotrexate, apremilast,dapsone) due to inadequate response or intolerance for at least 4 weeks prior tobeginning the study drug.

• Undergoing at least once a week standard of care wound care at home or wound carefacility.

• Willingness to travel to Oregon Health and Science University (OHSU) for all studyvisits, or living >30 miles from OHSU and willing/able to participate in remotevideoconferencing visits with access to a computer with internet and webcamcapabilities.

Exclusion Criteria:

• Have history of malignancy or lymphoproliferative disease; or have signs or symptomssuggestive of possible lymphoproliferative disease, including lymphadenopathy orsplenomegaly; or have active primary or recurrent malignant disease; or have been inremission from clinically significant malignancy for < 5years.

• Patients with cervical carcinoma in situ, basal cell carcinoma or squamous cellcarcinomas who have had active disease within 3 years of screening for this study.Active, untreated, acute or chronic infection (such as untreated tuberculosis), orimmunocompromised to an extent that such that participation in the study would posean unacceptable risk to the subject. (Treated infections such as latent tuberculosisafter completion of the appropriate therapy are not excluded.Patients currently ontreatment for active TB with drugs such as strong OAT-3 inhibitors will be excludedfrom study)

• Clinically serious infection or received intravenous antibiotics for an infection,within 4 weeks of randomization.

• Active viral infection that, based on the investigator's clinical assessment, makesthe subject and unsuitable candidate for the study.

• Positive for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus.

• Symptomatic herpes zoster infection within 12 weeks of screening or recurrent ordisseminated (even a single episode) herpes zoster.

• Symptomatic herpes simplex at the time of randomization or disseminated (even asingle episode) herpes simplex

• History of disseminated opportunistic infections (e.g., listeriosis andhistoplasmosis).

• Have a history of venous thromboembolism (VTE), or are considered at high risk forVTE as deemed by the investigator, or have 2 or more of the following risk factorsfor VTE:

1. Aged >65 years.

2. Body mass index (BMI) >35 kg/m2.

3. Oral contraceptive use and current smoker.

• Creatinine Clearance <30 mL/min

• Wound care debridement of any PG ulcer within 2 weeks.

• Intralesional corticosteroids within 4 weeks of screening.

• Previous exposure to a Janus kinase (JAK) inhibitor (ruxolitinib, tofacitinib,upadacitinib, filgotinib). For biologic therapies, the specific washout periods usedwill at least 4 weeks for anakinra, etanercept, infliximab, adalimumab, alefacept,golimumab, secukinumab, ixekizumab, risankizumab, guselkumab, tildrakizumab,canakinumab, ustekinumab and at least 24 weeks for rituximab or efalizumab.

• Patients who are currently on immunosuppressive therapies or have not discontinuedthem for at least 4 weeks.

• Clinically significant (per investigator's judgement) drug or alcohol abuse withinthe last 6 months preceding the Baseline Visit.

• Have a live vaccine within 12 weeks prior to baseline or intend to have a livevaccine during the course of study.

• Had any major surgery within 8 weeks prior to baseline or will require major surgeryduring the study, which in the opinion of the investigator would pose anunacceptable risk to the subject.

• Recent (within past 6 months) cerebrovascular accident, myocardial infarction,coronary stenting. Uncontrolled hypertension - confirmed systolic blood pressure >160 mmHg or diastolic blood pressure >100 mm Hg.

• Gastrointestinal (GI) perforation (other than appendicitis or penetrating injury),diverticulitis or significantly increased for GI perforation (within past 6 months)per investigator judgement; any condition could interfere with drug absorptionincluding but not limited to short bowel syndrome.

• Presence of significant uncontrolled respiratory, hepatic, renal, endocrine,hematologic, neurologic, or neuropsychiatric disorders, or abnormal laboratoryscreening values that, in the opinion of the investigator, pose an unacceptable riskto the subject if participating in the study or of interfering with theinterpretation of the data.

• Have clinical laboratory test results at screening that are outside the normalreference range of the population and are considered clinically significant, or haveany of the following specific abnormalities: Neutrophil count <1500 cells/µL,lymphocyte count <500 cells/µL, platelet count <100,000 cells/µL, aspartatetransaminase (AST) or alanine aminotransferase (ALT) > 2 times the upper limit ofnormal, hemoglobin <10 g/dL for male and female subjects, eGFR>60.

• Women who are lactating or breastfeeding.

• Have any other condition that precludes the subject from following and completingthe protocol, in the opinion of the investigator.

• Are investigator site personnel directly affiliated with this study and/or theirimmediate families (spouse, parent, child, or sibling).

• Are currently enrolled in, or discontinued from a clinical trial involving aninvestigational product or non-approved use of a drug or device within the last 4weeks or a period of at least 5 half-lives of the last administration of the drug,whichever is longer, or concurrently enrolled in any other type of medical researchjudged not to be scientifically or medically compatible with this study.

• History of myocardial infarction, stroke and New York Heart Association Stage II/IVheart failure

• Patients on concomitant medication with a Strong OAT-3 inhibitor for an existingcondition will be excluded from study