An Open-Label, Proof-of-Concept Study of Ixekizumab in the Treatment of Pyoderma Gangrenosum

This is a Phase II study that will be open label and include a total of five patients who will receive the investigational product. These patients will have histological testing to rule out competing etiologies and require 3rd party adjudication/confirmation on agreement of the diagnosis. These patients will undergo 12 weeks of ixekizumab dosed every 2 weeks with follow-up until week 16.

Inclusion criteria

• Major inclusion criteria:
• Have a clinical diagnosis of classic Pyoderma Gangrenosum for at least 3 months as determined by the investigator and an external reviewer on the basis of results from clinical, histological and laboratory assessments
• At screening, have a Pyoderma Gangrenosum ulcer characterized by 'item a' AND 3/5 features in 'item b' OR 2/5 features in 'item b' with support from one of the conditions listed in c.

a. Stable or increasing size within 2 months preceding screening by patient report or documentation b. Features such as violaceous border, undermining, d. Intralesional corticosteroids within 8 weeks of day 0; topical immunomodulators are permitted.

e. Wound debridement within 2 weeks of Day 0; dressing changes allowed per investigator discretion.

g. Systemic antibiotics within 2 weeks of Day 0 h. Live, attenuated vaccines within 3 months of Day 0; or live, seasonal-flu- or H1N1 vaccines within 2 weeks of Day 0. Note: recombinant- and/or killed vaccines are permitted.

i. Hyperbaric treatment within 4 weeks of Day 0 j. Investigational drug or investigational device within 30 days or 5 half-lives of Day 0, whichever is longer k. Prior exposure to ixekizumab l. Other treatments not described above should be maintained at a stable dose and frequency throughout the study as best as possible 13. Major, general surgery within 3 months of screening, or anticipated general surgery during the study period 14. Pregnancy, plans to become pregnant during the course of the study, delivery within 3 months of screening, or breast-feeding 15. If previous use of cyclosporine or systemic corticosteroids, failure to have any stabilization/response is exclusionary. This potentially indicates the disease is not Pyoderma Gangrenosum.

Exclusion criteria

• Major exclusion criteria:

• Any condition (e.g., psychiatric illness, severe alcoholism, or drug abuse) or situation that may compromise the ability of the subject to give written informed consent, may put the subject at significant risk, may jeopardize the subject's safety after exposure to the study drug, may confound the study results, or may interfere significantly with the subject's participation in the study
• History of malignancy within 2 years of screening other than carcinoma in situ of the cervix or adequately treated, non-metastatic, squamous or basal cell carcinoma of the skin
• History of seropositivity for HIV antibody; active or carrier status of hepatitis B [surface antigen (HBsAg) positive, or core antibody (anti-HBc) positive with negative surface antibody]; active hepatitis C (i.e. not treated or not cleared spontaneously, as confirmed by HCV PCR)
• History of severe allergic or anaphylactic reaction to monoclonal antibodies
• Systemic infection (excluding wound colonization) requiring oral antibiotics within 2 weeks of Day 0
• History of the following treatments:

• Anti-Tumor Necrosis Factor or other biologic therapies within 5 half-lives of screening
• Changes (addition, discontinuation, or changes in dose) in immunosuppressive medication (including cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, apremilast, dapsone, or corticosteroids) within 2 months of Day 0
• Systemic corticosteroids > 20 mg per day (prednisone or prednisone equivalent) within 8 weeks of Day 0, or change in dose within 8 weeks of Day 0. Steroids may be tapered (although not increased above the Day 0 dose) during the trial as determined by the investigator.

they are prescribed at stable doses for two months prior to baseline and are 20 mg or less per day of prednisone or other equivalently-dosed corticosteroids.

• Intralesional corticosteroids within 4 weeks of screening and during the study are not permitted 5. Other therapies that are non-immunosuppressive and non-investigational can be started or continued at physician discretion provided the medicine has no history of association with progressive multifocal leukoencephalopathy. Antibiotics may be used as needed for evidence of superinfection, positive culture results, malodor, green discharge, etc.