Efficacy and Safety of Tildrakizumab in the Treatment of Scalp Psoriasis

Inclusion Criteria:

1. Subjects should be 18 years or older at the time of signing the informed consentduring the Screening visit.
2. Subjects with a clinical diagnosis of chronic plaque psoriasis of at least 6 months (as determined by-subject interview and confirmation of diagnosis through physicalexamination by Investigator).
3. Subjects must have moderate to severe plaque psoriasis of the scalp at Screening andat Baseline, defined by:

• Scalp Investigator Global Assessment (IGA) of ≥3
• Psoriasis Scalp Severity Index (PSSI) score of ≥12
• ≥30% or scalp surface area affected.

4. Subject must have moderate to severe plaque psoriasis at Screening and Baselinedefined by

• Physician Global Assessment for Skin (PGA-S) of at least moderate severity (scoreof ≥3 on a 5-pointer scale)
• PASI score of ≥12
• Body Surface Area (BSA) involvement of >10%

5. Subjects must be considered candidates for systemic therapy, meaning scalp psoriasisinadequately controlled by topical treatments (corticosteroids), and/or phototherapy,and/or previous systemic therapy.
6. Subjects has a negative evaluation for tuberculosis (TB) within 4 weeks beforeinitiating study treatment, defined as a negative QuantiFERON® test. Subjects with apositive or 2 successive indeterminate. QuantiFERON® tests are allowed if they haveall of the following:

• No history of active TB or symptoms of TB.
• A posterior-anterior chest radiogram (with associated report available at studycenter) performed within 3 months of Screening with no evidence of active TB (orof any other pulmonary infectious diseases).
• If prior latent TB infection (LTBI), must have history of adequate prophylaxis (per local standard of care).
• If presence of LTBI is established, then treatment according to local countryguidelines must have been followed for 4 weeks prior to inclusion in the study. A maximum of 2 QuantiFERON® tests are allowed. A re-test is only permitted if thefirst is indeterminate; the result of the second test will then be used.

7. Subjects are unlikely to conceive, as indicated by at least one "Yes" answer to thefollowing questions:

• Subject is a male.
• Subject is a female and agrees to abstain from heterosexual activity OR use ahighly effective method of contraception as per Appendix 7.
• Male subjects with female partners of childbearing potential who are not usingbirth control as described above must use a barrier method of contraception (eg,condom) if not surgically sterile (ie, vasectomy).
• Subject is a surgically sterilized female or is documented to be postmenopausal.For contraceptive guidance see Appendix 7.

8. For women of childbearing potential, a negative serum pregnancy test at Screening anda negative urine pregnancy test within 24 hours prior to Day 1 and on subsequentvisits at which study treatment doses are scheduled.
9. Subjects must have results of a physical examination within normal limits orclinically acceptable limits to the Investigator prior to Day 1. The Investigator isencouraged to consult with the Medical Monitor (or appropriate designee) if there arequestions regarding the significance of any out-of-range values.
10. Subjects must be capable of giving signed informed consent as described in Appendix 2,which includes compliance with the requirements and restrictions listed in the ICF andin this protocol.

Exclusion Criteria:

1. Subjects who have laboratory abnormalities at Screening including any of thefollowing:

• Alanine aminotransferase or aspartate aminotransferase ≥2.5 × the upper limit ofnormal
• Creatinine ≥2 × the upper limit of normal
• Serum direct bilirubin ≥1.5 mg/dL
• White blood cell count <3.0×103/μL
• 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.

2. Subjects who have predominantly non-plaque forms of psoriasis specificallyerythrodermic psoriasis, predominantly pustular psoriasis, medication-induced ormedication-exacerbated psoriasis, or new-onset guttate psoriasis.
3. Women of childbearing potential who are pregnant, intend to become pregnant (within 6months of completing the study), or are lactating.
4. Subjects with any infection or history of recurrent infection requiring treatment withsystemic antibiotics within 2 weeks prior to Screening, or severe infection (eg,pneumonia, cellulitis, bone or joint infections) requiring hospitalization ortreatment with intravenous (IV) antibiotics within 6 weeks prior to Screening.
5. Subjects with any previous use of tildrakizumab or other IL-23/Th-17 pathwayinhibitors, including p40, p19 and IL-17 antagonists for psoriasis. • Prior use of TNF-alpha inhibitors with a wash-out period of 12 weeks would beallowed. However, the number of subjects with prior use of TNF-alpha inhibitors wouldbe capped at 40% and the analysis will be stratified based on prior use of thesebiologics.
6. Subjects with a positive human immunodeficiency virus test result, hepatitis B surfaceantigen, or hepatitis C virus test result.
7. Subjects with a prior malignancy or concurrent malignancy (excluding successfullytreated basal cell carcinoma, squamous cell carcinoma of the skin in situ, squamouscell carcinoma of skin with no evidence of recurrence within 5 years or carcinoma insitu of the cervix that has been adequately treated).
8. Subjects who have received live viral or bacterial vaccination within 4-weeks prior toBaseline or who intend to receive live viral or bacterial vaccination during thestudy.
9. Subjects who are currently participating in another interventional clinical study orhas participated in an interventional clinical study within 5-half-lives (of the drug)to wash-out prior to randomization (Subjects participating in observational studies ornon-interventional registry studies may be included in the study).
10. Subjects or a family member is among the personnel of the study center orSponsor/designee staff directly involved with this study.
11. Subjects who have any concomitant medical condition which in the opinion of theInvestigator could affect the study outcome or present an unacceptable risk.
12. Subjects who were hospitalized due to an acute cardiovascular event (such asmyocardial infarction, cerebrovascular accident, cardiovascular illness [eg, anginapectoris], or cardiovascular surgery [such as coronary artery bypass grafting]) within 6 months before Screening.
13. Subjects who, in the opinion of the Investigator, will not be a reliable participantin the study and those who can confound the results of the study.
14. Subjects who have a history of alcohol or drug abuse in the previous year.
15. Subjects who have high risk of suicidality at the Screening assessment based onInvestigator's judgment or, if appropriate, as indicated by a response of "yes" withinthe last 12 months to Questions 4 or 5 in the suicidal ideation section, or anypositive response in the behavioral section of the Columbia-Suicide Severity RatingScale
16. Subjects with any other clinically significant laboratory abnormality, which, in theopinion of the Investigator, will prevent the subject from completing the study orwill interfere with the interpretation of the study results.