Clinical trial NCT03668613: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Moderate to Severe Chronic Plaque-type Psoriasis
Keywords: pediatric
secukinumab
plaque psoriasis
AIN457A
Skin condition
skin disease
itching condition
psoriasis vulgaris
relapsing/remitting psoriasis
immune-mediated systemic disease
skin lesions
red skin lesions
scaly patches
papules
plaques
itching
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-09-12
Enrollment: 84
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number and Percentage of Participants With PASI 75 Response
timeFrame: Week 12
measure: Number and Percentage of Participants With IGA Mod 2011 0 or 1 Response
timeFrame: Week 12
Secondary outcomes:
measure: Number and Percentage of Participants With PASI 90 Response
timeFrame: Week 12
measure: Secukinumab Concentration in Serum
timeFrame: Baleine, Weeks 4, 12, 13, 14, 15, 16, 24, 52, 104, 156, 208
measure: Summary Table of Adverse Events
timeFrame: Adverse events are reported from the first dose of study-drug until the end of the treatment period (at Week 208) plus 16 weeks additional follow up reporting, for a maximum timeframe of approximately 224 weeks.
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: First OC Dermatology
state: California
city: Jacksonville
country: United States
facility: Private Practice
state: Florida
city: Lebanon
country: United States
facility: Novartis Investigative Site
state: New Hampshire
city: San Antonio
country: United States
facility: Texas Derm and Laser Specialists .
state: Texas
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Hradec Kralove
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Prague
country: Czechia
facility: Novartis Investigative Site
state: Prague 1
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
state: Mazowian
city: Rzeszow
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Krasnodar
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Esplugues De Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Magnolo N, Kingo K, Laquer V, Browning J, Reich A, Szepietowski JC, Keefe D, Papanastasiou P, Bao W, Forrer P, Patekar M. Efficacy of Secukinumab Across Subgroups and Overall Safety in Pediatric Patients with Moderate to Severe Plaque Psoriasis: Week 52 Results from a Phase III Randomized Study. Paediatr Drugs. 2022 Jul;24(4):377-387. doi: 10.1007/s40272-022-00507-0. Epub 2022 Jun 13.
citation: Magnolo N, Kingo K, Laquer V, Browning J, Reich A, Szepietowski JC, Keefe D, Mazur R, Ghelani P, Forrer P, Wraith L, Patekar M. A phase 3 open-label, randomized multicenter study to evaluate efficacy and safety of secukinumab in pediatric patients with moderate to severe plaque psoriasis: 24-week results. J Am Acad Dermatol. 2022 Jan;86(1):122-130. doi: 10.1016/j.jaad.2021.08.066. Epub 2021 Sep 30.