Clinical trial NCT03997786: A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Moderate-to-severe Chronic Plaque Psoriasis
Lead sponsor: Sun Pharmaceutical Industries Limited
Sponsor class: INDUSTRY
First posted: 2019-06-25
Enrollment: 130
Sex: ALL
Minimum age (years): 6
Maximum age (years): 215
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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

Primary outcomes:
measure: Part A - Maximum Plasma Concentration
timeFrame: Day 3, 7 and 28 following first dose
measure: Part A - Area under the plasma concentration-time curve
timeFrame: Day 3, 7 and 28 following first dose
measure: Part A - Maximum Plasma Concentration
timeFrame: Weeks 4,8, and 12 following second dose
measure: Part A - Area under the plasma concentration-time curve
timeFrame: Weeks 4,8, and 12 following second dose
measure: Proportion of subjects with at least 75% improvement in the PASI response from baseline
timeFrame: Week 12
measure: Proportion of subjects with PGA of "clear" or "almost clear" with at least a 2 grade reduction from baseline
timeFrame: Week 12
measure: Number of subjects with adverse events
timeFrame: Week 52
Secondary outcomes:
measure: Proportion of subjects achieving Psoriasis Area & Severity Index (PASI) 50 from baseline
timeFrame: Week 12, 16, 28, 40, 52, 64, 76 and 88
measure: Proportion of subjects achieving Psoriasis Area & Severity Index (PASI) 90 from baseline
timeFrame: Week 12, 16, 28, 40, 52, 64, 76 and 88
measure: Proportion of subjects achieving Psoriasis Area & Severity Index (PASI) 100 from baseline
timeFrame: Week 12, 16, 28, 40, 52, 64, 76 and 88
measure: Proportion of subjects achieving PASI 75 and PGA score of "clear" or "almost clear" with at least a 2 grade reduction from baseline
timeFrame: Week 16, 28, 40, 52, 64, 76 and 88
measure: Change in quality of life as measured by Children's Dermatology Life Quality Index (CDLQI)
timeFrame: Week 108
measure: Number of subjects with Adverse events
timeFrame: Week 108
measure: Immunogenicity - Anti-drug antibody status
timeFrame: Week 108
measure: Percent of subjects with severe infections
timeFrame: Week 108
measure: Percent of subjects with malignancies
timeFrame: Week 108
measure: Percent of subjects with confirmed major adverse cardiovascular events
timeFrame: Week 108
measure: Percent of subjects with drug- related hypersensitivity reactions
timeFrame: Week 108
Other outcomes:
measure: Relapse rates after withdrawal of treatment with tildrakizumab
timeFrame: Week 52
measure: Rebound rates after withdrawal of treatment with tildrakizumab
timeFrame: Week 52
measure: 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
timeFrame: Week 52
measure: 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
timeFrame: Week 52
measure: Maintenance of response - Proportion of subjects with at least 75% improvement in the PASI response from baseline
timeFrame: Week 52
measure: Maintenance of response - Proportion of subjects with PGA of "clear" or "almost clear" with at least a 2 grade reduction from baseline
timeFrame: Week 52
Locations:
city: Birmingham
country: United States
facility: Site 23
state: Alabama
city: Fountain Valley
country: United States
facility: Site 1
state: California
city: Thousand Oaks
country: United States
facility: Site 2
state: California
city: Clearwater
country: United States
facility: Site 4
state: Florida
city: Coral Gables
country: United States
facility: Site 24
state: Florida
city: Miami
country: United States
facility: Site 20
state: Florida
city: Miami
country: United States
facility: Site 7
state: Florida
city: Orlando
country: United States
facility: Site 12
state: Florida
city: Bay City
country: United States
facility: Site 5
state: Michigan
city: Troy
country: United States
facility: Site 16
state: Michigan
city: Saint Joseph
country: United States
facility: Site 22
state: Missouri
city: Dallas
country: United States
facility: Site 8
state: Texas
city: South Jordan
country: United States
facility: Site 10
state: Utah
city: Spokane
country: United States
facility: Site 14
state: Washington
city: Budapest
country: Hungary
facility: Site 63
city: Budapest
country: Hungary
facility: Site 62
city: Debrecen
country: Hungary
facility: Site 61
city: Kaposvar
country: Hungary
facility: Site 64
city: Szeged
country: Hungary
facility: Site 28
city: Ahmedabad
country: India
facility: Site 79
city: Ahmedabad
country: India
facility: Site 70
city: Chennai
country: India
facility: Site 78
city: Kolkata
country: India
facility: Site 75
city: Kolkata
country: India
facility: Site 76
city: Lucknow
country: India
facility: Site 71
city: Pune
country: India
facility: Site 73
city: Surat
country: India
facility: Site 74
city: Surat
country: India
facility: Site 77
city: Warangal
country: India
facility: Site 80
city: Bialystok
country: Poland
facility: Site 57
city: Gdańsk
country: Poland
facility: Site 55
city: Katowice
country: Poland
facility: Site 51
city: Lodz
country: Poland
facility: Site 54
city: Lodz
country: Poland
facility: Site 56
city: Lublin
country: Poland
facility: Site 58
city: Ostrowiec Swietokrzyski
country: Poland
facility: Site 50
city: Sosnowiec
country: Poland
facility: Site 59
city: Szczecin
country: Poland
facility: Site 52
city: Warszawa
country: Poland
facility: Site 53
city: Wrocław
country: Poland
facility: Site 40
city: Wrocław
country: Poland
facility: Site 39
city: Wrocław
country: Poland
facility: Site 38
city: Bardejov
country: Slovakia
facility: Site 92
city: Svidnik
country: Slovakia
facility: Site 91
city: Trnava
country: Slovakia
facility: Site 90
city: Barcelona
country: Spain
facility: Site 41
city: Las Palmas De Gran Canaria
country: Spain
facility: Site 47
city: Madrid
country: Spain
facility: Site 42
city: Valencia
country: Spain
facility: Site 44
city: Valencia
country: Spain
facility: Site 45
Study officials:
References: