Study to Evaluate the Safety and Tolerability of AC-1101 Topical Gel in Patients with Granuloma Annulare

Inclusion Criteria:

1. Patients 18 years of age or older, male or female, will be enrolled.

2. Diagnosis of granuloma annulare with supportive skin biopsy (diagnostic shave biopsyor punch biopsy) or historical biopsy (a provided report would be sufficient andwould not require to repeat the diagnostic biopsy). A biopsy at any point issufficient. If a diagnostic biopsy has never been performed, one will be performedprior to enrollment in the study. Patients with both localized and generalized GAwill be enrolled in the proposed study.

3. Other subtypes of GA, such as linear, perforating, and subcutaneous will be excludedfrom the study. If there is suspicion that GA is medication-induced, the patientwill not be enrolled. GA in association with human immunodeficiency virus (HIV) ormalignancy will be excluded.

4. Patients with 1-20% BSA of active Granuloma Annulare lesions will be enrolled.

5. Duration of active GA must be at least two years with no significant change in sizeor number of lesions in the 6 months prior to treatment as supported by acombination of record review and history/patient interview.

6. Patients who might be recalcitrant to or intolerant of conventional treatment, suchas antibiotics (e.g., doxycycline or minocycline), triple antibiotic therapy ofrifampin, ofloxacin, and minocycline, topical corticosteroids, topical calcineurininhibitors, intralesional/intramuscular corticosteroid and/or phototherapy.

7. Adequate organ function and marrow function meaured at screening (Visit 1) andenrollment (Visit 2) as defined below:

• Hemoglobin ≥ 12.0 g/dL for male and 10.5 g/dL for female;

• Absolute neutrophil count ≥ 1,300 /µL;

• Absolute lymphocytes: 1.0-4.0 x 109/L (1000-4000 cells/mm3) as the referencerange;

• Platelets ≥ 75,000/µL;

• Total bilirubin ≤ 1.5 x upper normal limit;

• AST(SGOT)/ALT(SGPT) ≤ 2.5 x upper normal limit;

• eGFR ≥ 60mL/min/1.73m2

8. Females of childbearing potential who are sexually active with a male partner mustbe willing to use one of the following acceptable contraceptive methods throughoutthe study and for 30 days after the last study drug administration.

• Intra-uterine contraceptive device without hormone release system placed atleast 4 weeks prior to study drug administration.

• Male partner using condom with intravaginally applied spermicide started atleast 21 days prior to study drug administration.

• Sterile male partner (vasectomized since at least 6 months).

• Barrier method of contraception: condoms (male or female) with or without aspermicidal agent, diaphragm or cervical cap with spermicide, bilateral tubalocclusion, sexual abstinence (when this is in line with preferred and usuallifestyle). No combined hormonal contraceptive methods (such as most oralpills, rings or patches) are permitted.

9. Capable of consent: Able to read, understand, and sign the Informed Consent Form (ICF), answer the study questionnaires, communicate with the Investigator, andunderstand and comply with protocol requirements.

10. Patients must speak English.

11. Patients must have health insurance.

Exclusion Criteria:

1. Patients with active malignancy will not be permitted to enroll in the proposedstudy. Patients with a history of treated nonmelanoma skin cancer will be eligibleto enroll.

2. Patients under treatment with biologics or other systemic immunosuppressivemedications (e.g., methotrexate (MTX), mycophenolate) within the last 3 months.

3. Presence of any clinically significant abnormality at physical examination,clinically significant abnormal laboratory assessment or positive test for hepatitisB (HBs-Ag), hepatitis C (HCV-Ab), or HIV found during medical screening.

4. History of allergic reactions to tofacitinib or other related drugs, or to anyexcipient in the formulation.

5. Positive pregnancy test at screening. If a woman becomes pregnant during the study,she will stop the study medication and be removed from the study. She will be urgedto follow up with her Primary Care Physician or obstetrician-gynecologist. The studydoctors will ask to follow the pregnancy to its outcome.

6. Women of childbearing potential who are unable or unwilling to use birth control (oral pills, rings or patches are not permitted) while taking the medication.

7. Pregnant or breast-feeding women.

8. Current active smokers.

9. Participation in a clinical research study involving the administration of aninvestigational or marketed drug or device within 30 days prior to the first dosing,administration of a biological product in the context of a clinical research studywithin 90 days prior to the first dosing, or concomitant participation in aninvestigational study involving drug or device administration.

10. History of active tuberculosis or exposure to endemic areas within 8 weeks prior toQuantiFERON®-TB testing performed at screening.

11. Positive QuantiFERON®-TB indicating possible tuberculosis infection.

12. Immunization with a live attenuated vaccine within 1 month prior to dosing orplanned vaccination during the study.

13. History of clinically significant opportunistic infection, e.g., invasive fungalinfections or pneumocystis pneumonia.

14. Serious local infection, e.g., cellulitis, abscess, or systemic infection, e.g.,septicemia, within 3 months prior to screening.

15. Use of medications for the timeframes specified below, with the exception ofmedications exempted by the Investigator on a case-by-case basis, such asAcetaminophen (2g in 24-hour period) because they are judged unlikely to affect thePK profile of the study drug or subject safety:

16. Prescription medications within 14 days prior to the first dosing with theexception of on-going medications to treat existing comorbid disorders, asjudged by the Investigator.

17. Topical medications inlcuding antibiotics or corticosteriod applied to thedesignated treatment area.

18. Depot injection or implant of any drug within 3 months prior to the firstdosing.

19. Any drugs known to significantly induce or inhibit hepatic drug metabolism viathe CYP3A4 and CYP2C19 enzymes within 30 days prior to first dosing.

20. Fever associated with a symptomatic viral or bacterial infection, within 2 weeksprior to the first dosing.

21. Subjects with a personal history of significant coronary heart disease, heartfailure, and/or cerebrovascular disease.

22. Any reason that, in the opinion of the Investigator, would prevent the subject fromparticipating in the study.