A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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The study has been designed with three components. Part A is an open label PK study followed by a randomized trial component (Part B) followed by open label Long Term Extension (LTE). The initial PK analysis is first done in adolescent subjects (12 to <18 years) before initiating the PK study in younger cohort (6 to <12 years)

Official Title
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A Multicenter, Randomized, Placebo and Active Comparator-controlled Clinical Trial to Study the Efficacy, Safety and Pharmacokinetics (PK) of Tildrakizumab in Pediatric Subjects From 6 to <18 Years of Age With Moderate to Severe Chronic Plaque Psoriasis

Conditions
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Moderate-to-severe Chronic Plaque Psoriasis

Intervention / Treatment
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* Drug: Tildrakizumab
* Drug: Placebo
* Drug: Tildrakizumab
* Drug: Tildrakizumab
* Drug: Tildrakizumab
* Drug: Etanercept
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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, meaning psoriasis inadequately controlled by topical treatments (corticosteroids), and/or phototherapy, and/or previous systemic therapy 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 surface (HBS) antigen, or hepatitis C virus (HCV) test result

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 215 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Part A<br>Part A is a DOSE FINDING COMPONENT: OPEN LABEL PK lead-in and safety component | Drug: Tildrakizumab<br>* Week 0 (Day 1), Week 4 (Day 28) and week 16 (Day 112)<br>|
| Experimental: Part B Part 1: Placebo and active comparator controlled study<br> | Drug: Placebo<br>* (Weeks 0 to 16)<br>Drug: Tildrakizumab<br>* (Weeks 0 to 16)<br>Drug: Etanercept<br>* (Weeks 0 to 16)<br>|
| Experimental: Part B-1 and B-2: Randomized withdrawal and retreatment after relapse<br> | Drug: Tildrakizumab<br>* (Weeks 16 to 52)<br>Drug: Placebo<br>* (Weeks 16 to 52)<br>|
| No Intervention: Part B 3: Efficacy and Safety Follow-up<br> | |
| Experimental: Part C: LTE<br> | Drug: Tildrakizumab<br>* at every 12 weeks in open label fashion till 5 years (240 weeks).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A - Maximum Plasma Concentration |  | Day 3, 7 and 28 following first dose | 
| Part A - Area under the plasma concentration-time curve |  | Day 3, 7 and 28 following first dose | 
| Part A - Maximum Plasma Concentration |  | Weeks 4,8, and 12 following second dose | 
| Part A - Area under the plasma concentration-time curve |  | Weeks 4,8, and 12 following second dose | 
| Proportion of subjects with at least 75% improvement in the PASI response from baseline |  | Week 12 | 
| Proportion of subjects with PGA of clear or almost clear with at least a 2 grade reduction from baseline |  | Week 12 | 
| Number of subjects with adverse events |  | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | Week 108 | 
| Number of subjects with Adverse events |  | Week 108 | 
| Immunogenicity - Anti-drug antibody status |  | Week 108 | 
| Percent of subjects with severe infections | 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 | Week 108 | 
| Percent of subjects with malignancies | including non-melanoma and melanoma skin cancer, but excluding carcinoma in situ of the cervix | Week 108 | 
| Percent of subjects with confirmed major adverse cardiovascular events | major adverse cardiovascular events | Week 108 | 
| Percent of subjects with drug- related hypersensitivity reactions | e.g. anaphylaxis, urticarial, angioedema, etc | Week 108 |