Moderate-to-severe Chronic Plaque Psoriasis
Conditions
Brief summary
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)
Interventions
DRUGTildrakizumab
Week 0 (Day 1), Week 4 (Day 28) and week 16 (Day 112)
DRUGPlacebo
(Weeks 0 to 16)
DRUGEtanercept
(Weeks 0 to 16)
Sponsors
Sun Pharmaceutical Industries Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The study will follow three distinct components: Open-label PK, blinded Randomized Trial Component (RCT) with open-label comparator followed by the open-label extension.
Eligibility
Sex/Gender
ALL
Age
6 Years to 215 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
Hungary, India, Poland, Slovakia, Spain, United States
Outcome results
None listed