Study to Assess the Long-term Safety, Tolerability, Efficacy of Secukinumab in Pediatric Patients of Age 6 to <18 Years, With Moderate to Severe Plaque Psoriasis

A Randomized, Open-label, Multicenter Trial to Assess the Efficacy of Subcutaneous Secukinumab after12 Weeks of Treatment, and to Assess the Long-term Safety, Tolerability, Efficacy in Subjects From 6 to <18 Years of Age With Moderate to Severe Chronic Plaque Psoriasis

This was an open-label, parallel-group, two-arm, multicenter study in pediatric subjects aged 6 years to less than 18 years, at randomization, with moderate to severe chronic plaque psoriasis. 84 subjects (most with moderate severity) were enrolled. Subjects were stratified by weight and disease severity.

This was an open-label, parallel group, two-arm, multi-center, trial in pediatric subjects aged 6 years to less than 18 years, at randomization, with moderate to severe chronic, plaque psoriasis. The study consists of 3 periods: screening (up to 4 weeks), treatment (Week 208) and post-treatment follow-up (Week 224).

Approximately 80 subjects (at least 60 subjects with moderate psoriasis) were planned to be enrolled in about 40 centers worldwide and targeted to have at least 5 subjects in the < 25kg body weight, and at least 10 subjects in each of the other two weight groups (25-< 50 kg and ≥ 50 kg). Adolescents (12-< 18 years) and children (6-< 12 years) were included from the beginning of this study, since the DMC had approved already the enrollment of children (6-< 12 years) in the study CAIN457A2310 (NCT02471144). Subjects received the appropriate dose based on their body weight category.

For the statistical analysis for outcome measures 1 and 2, there was no 'within study' control arm. A historical placebo control was obtained using data from qualifying trials and used as the comparator for the primary and key secondary endpoint analysis. This was in line with the guidance from and discussions with Health Authorities including FDA and EMA (PDCO), which suggested reducing placebo exposure as well as overall clinical trial burden for the pediatric population and accepted an extrapolation approach (EMA 2012). Historical placebo data included in this study were based on clinical appropriateness and alignment of definitions (endpoints, clinical disease population and time point of assessment). Integrated in the analysis were placebo data from Novartis-reported secukinumab adult placebo-controlled studies (CAIN457A2302 (NCT01544595 and NCT01365455), CAIN457A2303 (NCT01544595 and NCT01358578), CAIN457A2308 (NCT01555125) and CAIN457A2309 (NCT01636687)) and pediatric placebo-controlled study CAIN457A2310. In addition, pediatric placebo-controlled study data from the literature on other biologics (e.g. etanercept, ustekinumab) were utilized (Paller et al 2008, Landells et al 2015).

If the subject moved into a higher or lower weight group at two consecutive visits with weight measurements during the maintenance (from Week 12 onwards as assessed at 4 weekly visits or during extension treatment period (as assessed at scheduled site visits), then the subject was dosed according to the new (higher or lower) weight group respectively.

Inclusion Criteria:

1. Written informed assent and parental permission (age as per local law) obtained at screening before any assessment is performed.
2. Must be 6 to less than 18 years of age at the time of randomization
3. Moderate to Severe plaque psoriasis, defined as a PASI score ≥ 12, and IGA mod 2011 score of ≥ 3, and BSA involvement of ≥10%, at randomization.
4. Subject being regarded by the investigator to be a candidate for systemic therapy.

Exclusion Criteria:

1. Forms of psoriasis other than chronic plaque-type active at randomization
2. Drug-induced psoriasis
3. Ongoing use of prohibited treatments
4. Female subjects of childbearing potential defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing and for 16 weeks after stopping study treatment
5. Pregnant or nursing (lactating) females
6. Subjects with total WBC count <2,500/μL, or platelets <100,000/μL or neutrophils <1,500/μL or hemoglobin <8.5 g/dL at screening
7. Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or the IL-17 receptor