A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

• Tildrakizumab (Drug): Week 0 (Day 1), Week 4 (Day 28) and week 16 (Day 112)
• Placebo (Drug): (Weeks 0 to 16)
• Tildrakizumab (Drug): (Weeks 16 to 52)
• Tildrakizumab (Drug): at every 12 weeks in open label fashion till 5 years (240 weeks).
• Tildrakizumab (Drug): (Weeks 0 to 16)
• Etanercept (Drug): (Weeks 0 to 16)
• Placebo (Drug): (Weeks 16 to 52)

Primary outcomes

• Part A - Dose determination for pediatrics population 12 to <18-year-old age group [Up to week 16]
• Part A - Dose determination for pediatrics population 6 to <12 year-old age group [Up to week 16]
• Proportion of subjects with at least 75% improvement in the PASI response from baseline [Week 16]
• Proportion of subjects with PGA score of "clear" or "minimal" with at least a 2-grade reduction from baseline [Week 16]
• Number of subjects with adverse events [Week 16]

Secondary outcomes

• Proportion of subjects achieving Psoriasis Area & Severity Index (PASI) 50 from baseline [Week 12, 16, 28, 40, 52, 64, 76 and 88]
• Proportion of subjects achieving Psoriasis Area & Severity Index (PASI) 90 from baseline [Week 12, 16, 28, 40, 52, 64, 76 and 88]
• Proportion of subjects achieving Psoriasis Area & Severity Index (PASI) 100 from baseline [Week 12, 16, 28, 40, 52, 64, 76 and 88]
• Proportion of subjects achieving PASI 75 and PGA score of "clear" or "almost clear" with at least a 2 grade reduction from baseline [Week 16, 28, 40, 52, 64, 76 and 88]
• Change in quality of life as measured by Children's Dermatology Life Quality Index (CDLQI) [Week 108]: The CDLQI is a 10-item questionnaire that measures the impact of skin disease on children's (aged 2-15 years) quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The CDLQI total score was the sum of individual scores of question 1-10 and ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the children's life; 2-6 = small effect on the children's life; 7-12 = moderate effect on the children's life; 13-18 = very large effect on the children's life; 19-30 = extremely large effect on the children's life. Higher scores indicate more impact on quality of life of children.
• Number of subjects with Adverse events [Week 108]
• Immunogenicity - Anti-drug antibody status [Week 108]
• Percent of subjects with severe infections [Week 108]: defined as any infection meeting the regulatory definition of a serious adverse event, or any infection requiring IV antibiotics whether or not reported as a serious event as per the regulatory definition
• Percent of subjects with malignancies [Week 108]: including non-melanoma and melanoma skin cancer, but excluding carcinoma in situ of the cervix
• Percent of subjects with confirmed major adverse cardiovascular events [Week 108]: major adverse cardiovascular events
• Percent of subjects with drug- related hypersensitivity reactions [Week 108]: e.g. anaphylaxis, urticarial, angioedema, etc
• Number of subjects with adverse events [Week 52]

Other outcomes

• Relapse rates after withdrawal of treatment with tildrakizumab [Week 52]
• Rebound rates after withdrawal of treatment with tildrakizumab [Week 52]
• response to retreatment after relapse after withdrawal of treatment with tildrakizumab - Proportion of subjects with at least 75% improvement in the PASI response from baseline [Week 52]
• response to retreatment after relapse after withdrawal of treatment with tildrakizumab - Proportion of subjects with PGA of "clear" or "almost clear" with at least a 2 grade reduction from baseline [Week 52]
• Maintenance of response - Proportion of subjects with at least 75% improvement in the PASI response from baseline [Week 52]
• Maintenance of response - Proportion of subjects with PGA of "clear" or "almost clear" with at least a 2 grade reduction from baseline [Week 52]

Sex: All, ages: 6 Years to 215 Months

Inclusion Criteria:

* Subject must be 6 to < 18 years of age, of either sex, of any race/ ethnicity, must weight greater than or equal to 15Kg.
* Diagnosis of predominantly plaque psoriasis for ≥6 months (as determined by subject interview and confirmation of diagnosis through physical examination by investigator).
* Moderate to severe psoriasis at baseline defined as: at least 10% Body Surface Area (BSA) involvement, PGA score ≥ 3, and PASI score ≥ 12
* Subject must be considered a candidate for systemic therapy and/or phototherapy.
* Subject is considered to be eligible according to tuberculosis (TB) screening criteria
* A maximum of 2 QuantiFERON tests will be allowed. A re-test is only permitted if the first is indeterminate; the result of the second test will then be used.

Exclusion Criteria:

* Subject has predominantly non-plaque forms of psoriasis specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new-onset guttate psoriasis
* Subject has laboratory abnormalities at screening including any of the following: Alanine transaminase (ALT) or aspartate transaminase, (AST) ≥2X the upper limit of normal, Creatinine ≥1.5X the upper limit of normal serum direct bilirubin ≥ 1.5 mg/dL, white blood cell count < 3.0 x 103/μL, and any other laboratory abnormality, which, in the opinion of the Investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results
* Subject who is expected to require topical therapy, phototherapy, or additional systemic therapy for psoriasis during the trial
* Female subjects of childbearing potential who are pregnant, intend to become pregnant (within 6 months of completing the trial), or are lactating. (Sexually active adolescent girls will be required to use contraception)
* Subject with presence of any infection or history of recurrent infection requiring treatment with systemic antibiotics within 2 weeks prior to Screening, or severe infection (e.g. pneumonia, cellulitis, bone or joint infections) requiring hospitalization or treatment with IV antibiotics within 8 weeks prior to Screening
* Positive human immunodeficiency virus (HIV) test result, hepatitis B Virus (HBV) test results, or hepatitis C virus (HCV) test result
* Subjects who have a high risk of suicidality at the Screening assessment as indicated by the C-SSRS (Columbia Suicide Severity Rating Scale), or based on the Investigator's judgment.
* Subject who has received any of the prohibited medications, supplements or substances during the study.