Pediatric Study in Children and Adolescents With Severe Plaque Psoriasis
Condition: Chronic Severe Plaque-type Psoriasis
MeSH terms: Psoriasis
Study type: Interventional
Phase: Phase 3

Summary: 
      This was a multicenter, randomized, double-blind, placebo- and active-controlled (etanercept
      in single blinded arm) study in pediatric subjects aged 6 years to less than 18 years with
      severe chronic plaque psoriasis. Approximately 160 subjects aged 6 years to <18 years were
      enrolled, of which at least 30 were 6 years to <12 years old. Subjects were enrolled at
      approximately 70 study sites worldwide.
    

Detailed description: 
      The purpose of this study was to demonstrate superior efficacy of secukinumab versus placebo
      at Week 12, based on both PASI 75 and IGA mod 2011 0 or 1 response rates in children and
      adolescents aged 6 to less than 18 years with severe chronic plaque psoriasis who had
      inadequate control of symptoms with topical treatment, or failed to respond to or tolerate
      previous systemic treatment and/or UV therapy

      The study assessed the long term safety and tolerability of secukinumab in this pediatric age
      group and described the efficacy and safety of secukinumab compared to etanercept. This study
      provided efficacy and safety data to support the extension of label of secukinumab to include
      children and adolescents (6 years to <18 years) with severe chronic plaque psoriasis

      Two age subgroups were studied in a staggered approach within this clinical study: 12 to less
      than 18 years of age, and 6 to less than 12 years of age . Enrolment of children aged 6 to
      less than 12 years began after a favorable recommendation by an independent external Data
      Monitoring Committee (DMC) who reviewed data of approximately 80 adolescents. Adolescents
      continued to be recruited while the data from the first 80 subjects was being collected and
      analyzed

      Subjects were randomized using a 1:1:1:1 ratio into one of the treatment arms: secukinumab
      low dose, secukinumab high dose, etanercept or placebo. Subjects randomized to secukinumab
      treatment arms (high dose and low dose) received dose based on the weight category (<25 kg,
      25 to <50kg, ≥50 kg).

      The study consisted of 5 periods: screening (up to 4 weeks), induction (of 12 weeks),
      maintenance (of 40 weeks), extension treatment epoch (open-label of 184 weeks) and post-
      treatment follow-up epoch (of 16 weeks).

      The screening period of up to 4 weeks was used to assess eligibility of the patients and to
      taper patients off prohibited medications.

      The Induction period is defined as randomization through Week 12. In this period, the study
      was both active and placebo-controlled and at its completion, the primary endpoint was
      assessed (Week 12).

      The Maintenance period is defined as Week 12 (from dosing) through Week 52. During this
      period, the study was active-controlled, and the objectives focused on the maintenance of the
      response observed at Week 12.

      Patients who received secukinumab or etanercept during induction continued in maintenance
      with the same treatment. Patients who were on placebo during induction and at Week 12 were
      PASI 75 non-responders were switched to either secukinumab low dose or secukinumab high dose
      treatment group in the Maintenance period according to their baseline randomization.

      At the end of the Maintenance period, all patients on secukinumab entered the Extension
      treatment period and continued to receive the same dose of secukinumab. The Extension
      treatment period was defined as Week 52 (from dosing) until Week 236. In this period, all
      patients were treated with secukinumab, and the purpose was the collection of long-term
      safety and efficacy data.

      Patients who participated in the Maintenance period but prematurely discontinued the study
      were not able to enter the Extension treatment period. Patients receiving etanercept were not
      eligible to enter the Extension treatment period. Instead, at Week 52, they completed an EOM
      visit and then entered the post-treatment Follow-up period.
    

Intervention name(s): Experimental : Secukinumab low dose; Experimental: Secukinumab high dose; Placebo Comparator: Secukinumab Placebo; Active Comparator: Etanercept
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): Depending on weight group subject will receive per dose a) 75 mg if weighing less than 50 kg b) 150 mg if weighing 50 kg or more. Secukinumab injections (one or two per dose, depending on the weight group) will be administered subcutaneously at Randomization, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48, and Placebo secukinumab at Weeks 13, 14 and 15 during the blinded phase of the study; thereafter at Week 52 and every 4 weeks during the extension treatment period until Week 232.; Depending on weight group subject will receive per dose a) 75 mg if weighing less than 25 kg b) 150 mg if weighing between 25 and less than 50 kg c) 300 mg if weighing more than 50 kg. Secukinumab injections (one or two per dose, depending on the weight group) will be administered subcutaneously at Randomization, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48, and Placebo secukinumab at Weeks 13, 14 and 15 during the blinded phase of the study; thereafter at Week 52 and every 4 weeks during the extension treatment period until Week 232.; Placebo secukinumab (one or two subcutaneous injections per dose, depending on weight group) at Randomization and Weeks 1, 2, 3 4 and 8. At Week 12, subjects in the placebo group based on their PASI 75 response status at Week 12 will proceed as follows: • PASI 75 responders will discontinue study treatment at Week 12 and enter the treatment-free follow-up period • PASI 75 non-responders will receive high dose or low dose secukinumab, according to the pre-assignment at the Randomization visit. They will receive their treatment based on the weight category(<25 kg, 25- <50kg, ≥50 kg), on Weeks 12, 13, 14, 15, and then every four weeks starting at Week 16 until Week 48 during the maintenance period; thereafter at week 52 and every 4 weeks during the extension treatment period until Week 232.; Etanercept 0.8 mg/kg of subject weight and up to a maximum of 50 mg per dose. Subcutaneous etanercept 0.8 mg/kg (one or two injections per dose) once per week, for 51 weeks administered at home (self-injected or by caregiver) or at the study site. At Wk 52 subjects in the etanercept group will move into the treatment-free follow up period and terminate the study.
Other intervention name(s): AIN457 low dose; AIN457 high dose; AIN457 placebo; Etanercept
Intervention MeSH terms: Etanercept; Antibodies, Monoclonal
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: pediatric; chronic severe plaque psoriasis; secukinumab; etanercept