Exploring the Effects of IL-23 Inhibition by Risankizumab on Psoriasis Autoimmunity

Inclusion Criteria:

1. Subject has provided informed consent
2. Subject is > 18 and < 75 years of age at time of screening
3. Subject has had stable moderate to severe plaque psoriasis for at least 6 months (e.g., no morphology changes or significant flares of disease activity in the opinionof the Investigator)
4. Subject has involved body surface area (BSA) > 10% and PASI > 12 at baseline
5. Subject candidates to SKYRIZI therapy according to local label
6. Subject is able to complete study procedures, including self-assessments and selfinjections
7. Subjects who responded with T-lymphocytes proliferation to the psoriasis autoantigenLL37 or ADAMTSL5.
8. Subject is male or a woman not of child-bearing potential, including:
9. infertile patients due to surgical sterilization, congenital anomalies
10. OR postmenopausal, defined as: a woman of at least 50 years of age with an intactuterus, not on hormone therapy, who has either:

• Cessation of menses for at least 1 year
• OR At least 6 months of spontaneous amenorrhea with a follicle stimulatinghormone level of >40 mIU/mL

3. OR A woman of 55 years or older not on hormone therapy who has had at least 6months of spontaneous amenorrhea
4. OR A woman at least 55 years of age with a diagnosis of menopause prior tostarting hormone replacement therapy
5. Subject is a woman of child-bearing potential and:
6. Must test negative for pregnancy prior to first dose in Study
7. Must agree to either remain abstinent, if complete abstinence is their preferredand usual lifestyle, or remain in same-sex relationships, if part of theirpreferred and usual lifestyle, or without sexual relationships with males.Periodic abstinence (for example, calendar, ovulation, symptothermal,post-ovulation methods), declaration of abstinence just for the duration of atrial, and withdrawal are not acceptable methods of contraception.
8. OR Must use 2 effective methods of contraception for the entirety of the study.Abstinence or contraception must continue for 21 weeks following completion ofinvestigational product administration

• Two effective methods of contraception (such as male or female condoms withspermicide, diaphragms with spermicide or cervical sponges) will be used.The patient may choose to use a doublebarreled method of contraception.Barrier protection methods without concomitant use of a spermicide are not areliable or acceptable method. Thus, each barrier method must include use ofa spermicide. It should be noted that the use of male and female condoms asa double-barrier method is not considered acceptable due to the high failurerate when these methods are combined.
• Of note, 1 of the 2 methods of contraception may be a highly effective (lessthan 1% failure rate) method of contraception (such as, combination oralcontraceptives, implanted contraceptives or intrauterine devices).

Exclusion Criteria: Skin disease related:

1. Subject diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis,medication-induced psoriasis, or other skin conditions at the time of the screeningvisit (e.g., eczema) that would interfere with evaluations of the effect ofinvestigational product on psoriasis Other medical conditions:
2. Subject has a planned surgical intervention during the duration of the study
3. Subject has a known history of human immunodeficiency virus
4. Hepatitis B surface antigen or Hepatitis C antibody positivity at screening
5. Patient is hepatitis B core antibody positive (HBcAb+) but HbsAg and HBsAb negative
6. Subject has uncontrolled, clinically significant systemic disease such as diabetesmellitus, cardiovascular disease, renal failure, liver disease, or hypertension
7. Subject has any active malignancy, including evidence of cutaneous basal orsquamouscell carcinoma or melanoma
8. Subject has history of malignancy within 5 years except treated and considered curedcutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breastductal carcinoma
9. Subject has any concurrent medical condition that, in the opinion of the Investigator,could cause this study to be detrimental to the subject
10. Has active TB or other serious infection
11. Has received, or is expected to receive, any live virus or bacterial vaccinationwithin 4 weeks before the first administration of study intervention Laboratory abnormalities:
12. Laboratory abnormalities at screening, including any of the following:

• Hemoglobin < 9 g/dL
• Platelet count < 100,000/mm3
• White blood cell count < 3,000 cells/mm3
• Absolute neutrophil count (ANC) < 1000/mm3
• Creatinine clearance < 50 mL/min (Cockcroft-Gault formula)
• Any other laboratory abnormality, which, in the opinion of the Investigator, willprevent the subject from completing the study or will interfere with theinterpretation of the study results Washouts and non-permitted drugs:

13. Has received prior treatment with IL-12/23 inhibitor or IL23 inhibitor. Has receivedany with other biological agents for psoriasis without proper washout period of 4weeks.
14. Subject has used UV B therapy within 14 days before first dose of investigationalproduct
15. Subject has used topical therapy for psoriasis as follows:

• superpotent (class I) or potent (class II) topical steroids or topical anthralinwithin 14 days before first dose of investigational product
• any other formulation or potency of topical therapy or UV B phototherapy within 14 days before first dose of investigational product (exception: uppermid-strength to least potent [class III to VII] topical steroids permitted on thepalms, soles, face and intertriginous areas)

16. Subject has used the following within 28 days of first dose of investigationalproduct:

• UVA light therapy (with or without psoralen) or excimer laser;
• non-biologic systemic therapy for psoriasis (including but not limited to oralretinoids, cyclosporine, systemically administered calcineurin inhibitors,azathioprine, thioguanine, hydroxyurea, fumarates, or oral or parenteralcorticosteroids including intramuscular or intraarticular administration [exception: optic, nasal, or inhaled corticosteroids within recommended doses ispermitted])

17. Subject currently is enrolled in another investigational device or drug study, or lessthan 30 days since ending another investigational device or drug study(s), orreceiving other investigational agent(s) General
18. Active substance abuse (within 24 weeks of screening)
19. Has known intolerance or hypersensitivity to Risakizumab, or known allergies orclinically significant reactions.