A Study to Evaluate the Safety and Tolerability of PCS499 for the Treatment of Necrobiosis Lipoidica

Inclusion Criteria

• Male or female patients age 18 to 80 years of age, inclusive, at Screening.
• Biopsy-confirmed diagnosis of NL. Biopsies of continually active lesions performed outside of this clinical study will need to be reviewed and the diagnosis confirmed by the study pathologist. For patients with no previous history of biopsy, no biopsy within the previous 5 years, a biopsy that is not confirmed to be NL, or newly active lesion, a biopsy to confirm a diagnosis of NL will be performed at the Screening visit.
• Reference NL lesion with a score of 2 or greater on the Investigator Global Assessment: Necrobiosis Lipoidica (IGA:NL) Activity scale AND surface area with minimum size of 10 cm2. If more than one lesion is present, the reference lesion area is the lesion with the highest disease severity.
• Women of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at Baseline before dosing.
• Women of childbearing potential must use one of the following acceptable methods of contraception throughout the study: oral contraceptive medication, intrauterine device (IUD), hormonal implants, injectable contraceptive medications, double-barrier methods, or tubal ligation.
• Females who are postmenopausal (age-related amenorrhea >= 12 consecutive months and increased follicle-stimulating hormone [FSH] > 40 mIU/mL. If necessary to confirm postmenopausal status, an FSH will be drawn at Screening) or who have undergone hysterectomy or bilateral oophorectomy are exempt from pregnancy testing.
• Male patients must be willing to use appropriate contraceptive measures and refrain from sexual activity with any female who is pregnant or lactating.
• Patient must be willing and able to swallow whole tablets.
• Patient must be willing and able to comply with study procedures.
• Patient must be willing and able to provide signed, informed consent.

Exclusion Criteria

• Current or previous (within 4 weeks of Baseline) treatment with:
• Oral, topical, or intralesional corticosteroids;
• Systemic pentoxifylline, theophylline, or cilostazol
• Oral or topical retinoid;
• Other systemic or topical immunosuppressant drugs, including but not limited to calcineurin inhibitors (e.g., tacrolimus), thalidomide, apremilast, anti-malarials (e.g., hydroxychloroquine, chloroquine), cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, etc.
• Current or previous (within 12 weeks of Baseline) treatment with any biologic therapy (e.g., adalimumab, etanercept, infliximab, anakinra, etc.).
• Phototherapy/photochemotherapy (NBUVB, UVB, PUVA) within 6 weeks prior to Baseline
• Skin grafting, or other surgical procedure (other than debridement) within 6 weeks prior to Baseline.
• History of drug allergy, including but not limited to pentoxifylline or other xanthine derivatives, or other allergy, which in the opinion of the Investigator, contraindicates participation.
• Anticipated concurrent use of a strong CYP1A2 inhibiting drug, including but not limited to cimetidine and/or fluvoxamine, during the course of the study (after Screening).
• Fever (>38°C), or chronic, persistent, or recurring infection(s) at Screening or Baseline.
• Any infection requiring oral antimicrobial therapy within 2 weeks prior to Baseline or any infection requiring parenteral antibiotics or hospitalization within 12 weeks prior to Baseline. Any treatment for such infections must have been completed and the infection cured for at least 2 weeks prior to Baseline.
• History of sarcoidosis, pyoderma gangrenosum, or any other disorder (in the judgment of the Investigator) that would interfere with the evaluation of NL or require protocol prohibited medication.
• History of any life threatening infection or sepsis within 12 months of Baseline:
• Clinically significant cardiac disease including but not limited to unstable angina, acute myocardial infarction within 6 months of Baselin